Lixumia (Lixumiya) cov lus qhia rau siv > Kev khomob thiab kev tiv thaiv

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

1 ml
lixisenatide	0.05 mg

Tshwjxeeb: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid daws 1 M lossis sodium hydroxide daws 1 M - txog pH 4.5, dej d / thiab - txog 1 ml.

3 ml - cartridges (1) - syringe cwjmem (1) - pob ntawm cardboard.

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

1 ml
lixisenatide	0.1 mg

3 ml - cartridges (1) - syringe cwjmem (1) - pob ntawm cardboard.
3 ml - cartridges (1) - syringe cwjmem (2) - pob ntawm cardboard.
3 ml - cartridges (1) - syringe cwjmem (6) - pob khoom ntawm cardboard.

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

1 ml
lixisenatide	0.05 mg

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

1 ml
lixisenatide	0.1 mg

3 ml - cartridges (2) nrog daws 0.05 mg / ml (10 μg / koob) thiab 0.1 mg / ml (20 μg / koob) - koob txhaj tshuaj (2) - pob ntawm cardboard.

Kev ntsuas rau siv

Hom 2 mob ntshav qab zib mellitus rau cov neeg laus kom tau txais glycemic tswj nyob rau hauv cov neeg mob uas mob ntshav qab zib mellitus tsis tswj hwm los ntawm kev kho ntshav qab zib tas mus li.

Lub hom phiaj ntawm Lixumia ua ke nrog cov tshuaj hauv qab no hauv qhov ncauj hypoglycemic yog qhia:

- qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg,

- kev sib txuas ntawm cov tshuaj no.

Lixumia kuj tseem nyob nrog kev sib xyaw nrog basal insulin:

- nyob rau hauv ua ke nrog ib qho tshuaj hypoglycemic qhov ncauj ntawm sulfonylurea pab pawg.

Cov Yuav Tsum Tau Ua

- Kom ib tug neeg rhiab los ntawm cov tshuaj nquag lossis ib qho tshaj tawm ntawm cov tshuaj.

- Lub sijhawm lactation (kev pub niam mis).

- Muaj mob hnyav rau ntawm txoj hnyuv, nrog rau mob plab.

- Kev mob raum tsis zoo (ua kom muaj cov ntshav tshem tawm tsawg dua 30 ml / min).

- Cov menyuam yaus thiab tub ntxhais hluas uas muaj hnub nyoog qis dua 18 xyoo.

Nrog keeb kwm ntawm tus mob pancreatitis, Lixumia yuav tsum siv nrog ceev faj.

Yuav siv li cas: noj ntau thiab hom tshuaj kho

Thawj koob tshuaj Lixumia yog 10 mcg ib hnub ib zaug rau 14 hnub. Tom qab ntawd cov koob tshuaj yuav tsum tau nce rau cov tshuaj txij nkawm ntawm 20 mcg ib hnub ib zaug.

Thaum cov tshuaj ntxiv rau txuas ntxiv kev kho mob metformin, metformin tuaj yeem txuas ntxiv yam tsis hloov nws cov koob tshuaj.

Thaum Lixumia ntxiv rau qhov kev kho mob uas twb muaj lawm nrog kev kho qhov ncauj hypoglycemic ntawm sulfonylurea pawg lossis los ua ke nrog cov tshuaj tiv thaiv qhov ncauj ntawm sulfonylurea pab pawg thiab insulin basal, qhov kev txo qis ntawm qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg lossis basal insulin tuaj yeem suav tias yog txo cov kev pheej hmoo ntawm hypoglycemia.

Kev siv Lixumia tsis tas yuav tsum muaj kev saib xyuas tshwj xeeb ntawm kev saib xyuas cov kua nplaum hauv cov ntshav. Txawm li cas los xij, thaum siv los ua ke nrog kev noj tshuaj ntawm qhov ncauj ntawm sulfonylurea pawg lossis basal insulin, tshuaj xyuas cov ntshav qabzib concentration lossis kev tswj tus kheej (tswj hwm los ntawm tus neeg mob) ntawm cov ntshav qabzib concentration yuav tsum tau kho qhov tshuaj ntawm qhov ncauj hypoglycemic tshuaj ntawm sulfonylurea pawg lossis basal insulin.

Cov pab pawg neeg tshwj xeeb

Cov menyuam yaus thiab cov tub ntxhais hluas hnub nyoog qis dua 18: tam sim no, kev nyab xeeb thiab kev ua haujlwm ntawm cov tshuaj hauv pawg neeg mob no tseem tsis tau kawm.

Cov muaj hnub nyoog: tsis tas yuav txhaj koob tshuaj hloov raws lub hnub nyoog ntawm tus neeg mob.

Cov neeg mob mob rau daim siab tsis ua hauj lwm: tsis tas yuav tsum txhaj tshuaj rau hauv cov neeg mob lub siab tsis ua hauj lwm.

Cov neeg mob lub raum tsis ua haujlwm: tsis tas yuav tsum txhaj tshuaj rau hauv cov neeg mob lub raum tsis ua haujlwm me me (kev tsim kho lub peev xwm 50-80 ml / min) thiab mob raum tsis ua haujlwm (creatinine tshem tawm 30-50 ml / min). Tsis muaj kev paub txog kev kho mob nrog Lixumia hauv cov neeg mob uas lub raum tsis ua haujlwm loj (kev tshem tawm tsis zoo li 30 ml / min) lossis nrog kev mob raum tsis ua haujlwm, thiab yog li ntawd kev siv cov tshuaj hauv pawg neeg mob no yog sib kis.

Lixumia muab rau noj 1 zaug nyob hauv ib hnub li 1 teev ua ntej noj mov thawj hnub lossis ua ntej 1 teev ua ntej noj mov. Yog tias cov koob tshuaj ntxiv hla, nws yuav tsum raug tswj ua ntej 1 teev ua ntej noj mov tom ntej.

Cov tshuaj yog muab tshuaj subcutaneously hauv tus ncej puab, plab phab ntsa lossis xub pwg. Lixumia yuav tsum tsis txhob muab rau cov tshuaj pleev ib ce lossis ib qho intramuscularly.

Ua ntej siv, Lixumia koob txhaj tshuaj yuav tsum tau muab cia rau hauv tub yees ntawm qhov kub ntawm 2-8 ° C hauv nws cov khoom ntim kom tiv thaiv nws los ntawm kev nphav raug. Tom qab siv thawj zaug, rab koob xaum yuav tsum khaws cia ntawm qhov kub tsis tshaj 30 ° C. Tom qab siv txhua zaus, rab koob xaum xaum yuav tsum tau kaw nrog lub hau kom tiv thaiv nws ntawm kev chwv lub teeb. Daim xaum xaum yuav tsum tsis txhob muab nrog lub koob txuas. Tsis txhob siv cov xwj xem hluav taws xob yog tias nws tau khov.

Tus Lixumia Syringe Cwj mem yuav tsum muab pov tseg tom qab 14 hnub.

Pharmacological kev txiav txim

Kev nquag ua haujlwm ntawm Lixumia lixisenatide yog qhov muaj zog thiab xaiv cov agonist ntawm glucagon-zoo li peptide receptors-1 (GLP-1). GLP-1 receptor yog lub hom phiaj rau haiv neeg GLP-1, lub cev endogenous ntawm kev ua haujlwm sab hauv, uas potentiates qabzib-insulin secretion los ntawm beta-cells ntawm pancreatic islets. Cov nyhuv ntawm lixisenatide cuam tshuam nrog nws cov kev sib txuam nrog GLP-1 receptors, ua rau muaj kev nce ntxiv ntawm cov ntsiab lus intracellular ntawm cyclic adenosine monophosphate (cAMP). Lixisenatide stimulates lub zais insulin los ntawm beta hlwb ntawm pancreatic islets nyob rau hauv teb rau hyperglycemia. Thaum cov concentration ntawm cov piam thaj hauv cov ntshav txo qis rau qhov tseem ceeb, qhov kev xav ntawm insulin secretion ceases, uas txo cov kev pheej hmoo ntawm hypoglycemia. Hauv hyperglycemia, lixisenatide ib txhij suppresses tso pa tawm ntawm glucagon, txawm li cas los xij, kev tiv thaiv cov tshuaj tiv thaiv ntawm glucagon secretion nyob rau hauv teb rau hypoglycemia tseem nyob.

Ib qho kev paub zoo rau insulinotropic kev ua ntawm lixisenatide tau qhia, suav nrog kev nce ntawm insulin biosynthesis thiab kev ua kom lub cev ntawm cov hlwb beta ntawm pancreatic islets hauv cov tsiaj. Lixisenatide qeeb qeeb ua kom lub plab zom mov, thiaj li txo qis kev nce hauv cov piam thaj hauv ntshav tom qab noj mov. Qhov ua rau lub plab zom mov tuaj yeem pab txhawb kom poob phaus.

Thaum muab ib hnub ib zaug rau cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, lixisenatide txhim kho glycemic tswj vim muaj kev txhim kho sai tom qab nws txoj kev tswj hwm thiab lub sijhawm ntev txo hauv cov ntshav qabzib concentration tom qab noj mov thiab ntawm lub plab tas.

Tso tawm daim ntawv, muaj pes tsawg leeg thiab ntim khoom

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

Hauv 1 ml ntawm kev daws muaj:

cov tshuaj nquag: lixisenatide - 0.05 mg,

kev zam: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid daws 1 M lossis sodium hydroxide daws 1 M - txog pH 4.5, dej d / thiab - txog 1 ml

3 ml - cartridges (1) - syringe cwjmem (1) - pob ntawm cardboard.

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

Hauv 1 ml ntawm kev daws muaj:

cov tshuaj nquag: lixisenatide - 0.1 mg,

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

Hauv 1 ml ntawm kev daws muaj:

cov tshuaj nquag: lixisenatide - 0.05 mg,

Kev daws rau sc tswj hwm yog pob tshab, xim tsis muaj zog.

Hauv 1 ml ntawm kev daws muaj:

cov tshuaj nquag: lixisenatide - 0.1 mg,

3 ml - cartridges (2) nrog daws 0.05 mg / ml (10 μg / koob) thiab 0.1 mg / ml (20 μg / koob) - koob txhaj tshuaj (2) - pob ntawm cardboard.

Hom 2 mob ntshav qab zib mellitus rau cov neeg laus kom tau txais glycemic tswj nyob rau hauv cov neeg mob uas mob ntshav qab zib mellitus tsis tswj hwm los ntawm kev kho ntshav qab zib tas mus li.

Lixumia yog qhia ua ke nrog cov tshuaj hauv qab no hauv qhov ncauj hypoglycemic:

- qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg,

- kev sib txuas ntawm cov tshuaj no.

Lixumia yog qhia nrog cov kua dej hauv paus:

- ua ke nrog metformin,

- nyob rau hauv ua ke nrog ib qho tshuaj hypoglycemic qhov ncauj ntawm sulfonylurea pab pawg.

Kev siv Lixumia thaum cev xeeb tub thiab lactation

Cov poj niam muaj hnub nyoog yug menyuam.
Lixumia tsis pom zoo rau cov poj niam ntawm lub hnub nyoog yug menyuam uas tsis siv tshuaj txwv.
Cev xeeb tub
Muaj cov ntaub ntawv tsis txaus ntawm kev siv Lixumia hauv cov poj niam cev xeeb tub. Kev kawm ua ntej pom tau hais tias muaj tshuaj lom deev.
Peb paub tsis meej tias yuav muaj xwm txheej dabtsi rau tib neeg.
Lixumia yuav tsum tsis txhob siv thaum cev xeeb tub. Hloov, insulin yog qhov pom zoo.
Yog tias tus neeg mob xav ua lub cev xeeb tub los yog cev xeeb tub tau tshwm sim, kev kho mob nrog Lixumia yuav tsum tsis ua mus ntxiv.
Lactation.
Kuj tsis paub meej tias Lixumia puas kis tau tib neeg cov kua mis. Lixumia yuav tsum tsis txhob siv thaum lactation.
Cuam Tshuam.
Kev kawm ua ntej tsis tau qhia paub hais tias muaj kev phom sij txog kev muaj tub muaj ki.

Lixisenatide yog qhov xaiv cov agonist ntawm GLP-1 receptors (glucagon-zoo li peptide-1). GLP-1 receptor yog lub hom phiaj rau haiv neeg GLP-1, ib qhov kev loj hlob ntawm endogenous hormone uas potentiates qabzib-insulin secretion los ntawm pancreatic beta hlwb.
Cov txiaj ntsig ntawm lixisenatide yog kev sib kho los ntawm kev sib cuam tshuam tshwj xeeb nrog cov receptors GLP-1, uas ua rau muaj kev nce ntxiv ntawm intracellular cyclic adenosine monophosphate (cAMP).
Lixisenatide stimulates insulin secretion thaum cov ntshav qab zib cov ntshav nce siab, tab sis tsis nrog normoglycemia, uas ua rau muaj kev pheej hmoo ntawm hypoglycemia.
Tib lub sijhawm, glucagon zais cia yog suppressed. Nrog lub qog ntshav qab zib, lub zog cia ntawm glucagon zais cia yog tswj.
Lixisenatide ua rau kom lub plab khiav tawm hauv lub plab, txo kev nrawm nrawm uas cov piam thaj tau los ntawm cov zaub mov hauv cov ntshav.
Cov teeb meem Pharmacodynamic.
Thaum siv ib zaug ib hnub rau cov neeg mob uas muaj ntshav qab zib hom 2, lixisenatide txhim kho glycemic tswj vim muaj kev cuam tshuam sai thiab ntev ntawm kev txo qis qabzib ntau tom qab noj mov thiab hauv plab tas.
Cov nyhuv ntawm cov kua qab zib tom qab tau pom tseeb hauv kev tshawb nrhiav 4 lub lim tiam, hauv kev sib piv nrog liraglutide 1.8 mg ib hnub ib zaug ua ke nrog metformin. Txo los ntawm theem pib ntawm PPK qhov taw qhia 0: 30–4: 30 h
ntshav qabzib tom qab noj mov tau yog:
–12.61 teev * mmol / L (-227,25 teev * mg / dL) hauv cov pab pawg lixisenatide thiab –4.04 teev * mmol / L (–72.83 teev * mg / dl) hauv pab pawg liraglutide.
Qhov no kuj tau lees paub hauv kev tshawb nrhiav 8 lub lim tiam piv rau liraglutide tshuaj ua ntej noj tshais ua ke nrog cov tshuaj insulin glargine nrog lossis tsis muaj metformin.
Cov chaw soj ntsuam kev ua tau zoo thiab kev nyab xeeb.
Qhov cuam tshuam ntawm Lixumia ntawm kev tswj glycemic piv nrog exenatide tau raug ntsuas hauv rau (6) randomized, ob chav dig muag, qhov kev sim tshuaj uas tau txiav txim siab thiab ib qho randomized, qhib-daim ntawv lo tshawb kawm nrog kev tswj tau nquag.
Cov kev tshawb fawb muaj xws li 3825 cov neeg mob uas muaj ntshav qab zib hom 2 (2445 cov neeg mob tau siv los siv lixisenatide), 48.2% ntawm tus txiv neej thiab 51.8% ntawm cov poj niam.
768 cov neeg mob (447 randomized siv lixisenatide) yog ≥65 xyoo, thiab cov neeg mob 103 (57 randomized siv lixisenatide) muaj hnub nyoog ≥75 xyoo.
Hauv kev ua tiav theem III cov kev tshawb fawb, nws tau sau tseg tias thaum kawg ntawm lub sijhawm 24-lub lim tiam ntawm kev kho mob, ntau dua 90% ntawm cov neeg mob tau tuaj yeem tswj kev saib xyuas ntawm Lixumia 20 μg ib hnub ib zaug.
Glycemic tswj.
Muaj kev sib txuas ntxiv ua ke siv cov tshuaj tiv thaiv kab mob hauv qhov ncauj.
Thaum kawg ntawm kev kho mob 24 lub lis piam, Lixumia sib xyaw nrog metformin, sulfonylurea, pioglitazone, lossis kev sib xyaw ntawm cov tshuaj no tau qhia txog qhov kev poob qis tseem ceeb hauv kev yoo plasma HbA1c, yoo qab zib thiab 2-teev postprandial qab zib tom qab noj zaub mov sib piv nrog cov placebo. Kev txo qis hauv HbA1c yog qhov tseem ceeb thaum cov tshuaj tau txhaj ib hnub ib zaug, tsis hais nws siv thaum sawv ntxov lossis thaum yav tsaus ntuj.
Qhov kev kis tus kab mob HbA1c no tau siv sijhawm ntev nyob rau hauv cov kev tshawb fawb mus sij hawm ntev ntev txog li 76 lub lis piam.
Kev kho mob ntxiv rau hauv kev sib xyaw ua ke tshwj xeeb nrog metformin.
Cov lus 2: Cov kev tshawb fawb tshuaj placebo hauv kev ua ke nrog metformin (cov txiaj ntsig 24-lub lim tiam).
Hauv kev kawm nrog kev tswj hwm thaum xaus ntawm lub ntsiab 24-lub lim tiam kho lub sijhawm, kev siv Lixumia ib hnub ib zaug qhia tau txo HbA1c qib -0.79% piv rau -0.96% nrog exenatide ob zaug hauv ib hnub, nrog qhov nruab nrab sib txawv hauv kev kho 0.17% (95% kev sib ntseeg siab (CI): 0.033, 0.297) thiab qhov feem pua zoo sib xws ntawm cov neeg mob uas ua tiav HbA1c qib qis dua 7% hauv pawg lixisenatide (48.5%)
thiab hauv pawg exenatide (49.8%).
Lub sijhawm 24 lub lim tiam ntawm kev kho mob, qhov tshwm sim ntawm xeev siab yog 24.5% nyob rau hauv cov pab pawg lixisenatide piv rau 35.1% hauv pawg exenatide ib hnub ob zaug, thiab qhov tshwm sim ntawm cov tsos mob hypoglycemia nrog lixisenatide yog 2.5% piv nrog 7.9% hauv pawg exenatide.
Hauv 24-lub lim tiam qhib daim ntawv qhia, lixisenatide tau muab ua ntej noj mov tseem ceeb thiab tsis qis dua lixisenatide tau muab ua ntej noj tshais ua ib feem ntawm kev txo qis.
HbA1c (kev hloov pauv hauv qhov kev txwv ntawm lub ntsiab lus los ntawm thawj qib: -0.65% piv nrog 0.74%). Txawm hais tias qhov noj tsawg hauv HbA1c losxij txawm hais tias tseem noj mov tseem ceeb (tshais, pluas su, lossis hmo). Thaum kawg ntawm txoj kev tshawb no, 43.6% (cov pab pawg noj mov tseem ceeb) thiab 42.8% (pawg ua tshais) ntawm cov neeg mob ua tiav tsawg dua 7% HbA1c. Xeev siab tau qhia tawm hauv 14.7% thiab 15.5% ntawm cov neeg mob, thiab cov tsos mob ntawm tus mob ntshav qab zib hauv 5.8% thiab 2.2% ntawm cov neeg mob nyob hauv cov zaub mov tseem ceeb thiab noj tshais, feem.
Cov kev kho mob ntxiv hauv kev sib xyaw ua ke tshwj xeeb nrog sulfonylurea lossis siv ua ke nrog metformin.
Cov lus 3: Cov kev kawm tso tshuaj placebo nrog sulfonylurea (cov txiaj ntsig 24-lub lim tiam).
Cov kev kho mob ntxiv hauv kev sib xyaw ua ke nrog tshwj xeeb nrog pioglitazone lossis ua ke nrog metformin.
Hauv kev soj ntsuam hauv cov neeg mob uas tsis ua tiav kev tswj hwm ntawm pioglitazone, ntxiv ntawm lixisenatide rau pioglitazone ntxiv nrog lossis tsis muaj tshuaj metformin nyob rau thaum xaus ntawm lub ntsiab 24-lub lim tiam kho ua rau HbA1c los ntawm lub hauv paus los ntawm 0.90% piv nrog qhov txo qis los ntawm theem pib ntawm 0.34% hauv pawg placebo. Thaum kawg ntawm lub sijhawm 24-lub lim tiam kho mob, 52.3% ntawm cov neeg mob tau txais lixisenatide muaj HbA1
c tau qis dua 7% piv nrog 26.4% hauv cov pawg placebo.
Thaum lub sijhawm 24 lub lis piam kev kho mob, xeev siab tau pom nyob hauv 23.5% nyob rau hauv cov pab pawg lixisenatide piv nrog 10.6% hauv cov pawg placebo, cov mob ntawm hypoglycemia hauv 3.4% ntawm cov neeg mob kho lixisenatide, piv nrog 1.2% hauv pawg placebo.
Cov kev kho mob ntxiv nrog kev noj qab haus huv nrog basal insulin Lixumia, tau sau ua ke nrog insulin basal insulin ib leeg, lossis kev sib xyaw nrog basal insulin thiab metformin, lossis kev sib xyaw nrog basal insulin thiab sulfonylurea, ua rau muaj kev cuam tshuam tseem ceeb hauv HbA1c thiab 2-teev tom qab qab zib tom qab kuaj noj mov tiv tiag cov placebo.
Cov lus 4: Cov kev tshawb fawb tshuaj placebo hauv kev sib xyaw nrog cov tshuaj insal hauv paus (cov txiaj ntsig 24-lub lim tiam).
Ib qho kev tshawb fawb soj ntsuam raug ua rau cov neeg mob uas tsis tau txais insulin yav dhau los, uas tsis muaj kev tswj hwm ntawm cov tshuaj tiv thaiv kab mob hauv qhov ncauj. Txoj kev tshawb no muaj 12 lub lis piam npaj ua ntej nrog insulin glargine tswj hwm thiab titration thiab 24-lub sijhawm kho mob thaum lub sijhawm cov neeg mob tau txais lixisenatide lossis placebo ua ke nrog insulin glargine thiab metformin nrog lossis tsis muaj thiazolidinediones. Thaum lub sijhawm no, cov tshuaj insulin glargine tau ua ntu zus tas li.
Lub sijhawm 12 lub lis piam npaj, lub sijhawm ntxiv thiab lub cev ntawm insulin glargine ua rau HbA1c kwv yees li 1%.
Qhov sib ntxiv ntawm lixisenatide ua rau txo qis HbA1 ntau dua los ntawm 0.71% hauv pawg lixisenatide piv nrog 0.40% hauv cov pab pawg placebo. Thaum kawg ntawm lub sijhawm 24-lub lim tiam ntawm kev kho mob, 56.3% ntawm cov neeg mob siv lixisenatide tau qhab nia HbA1 tsawg dua 7% piv rau 38.5% hauv cov pawg placebo.
Hauv lub sijhawm 24-lub lim tiam kho mob, 22.4% ntawm cov neeg mob kho nrog lixisenatide qhia tsawg kawg yog ib qho kev mob tshwm sim, piv rau 13.5% hauv cov tshuaj placebo.
Qhov xwm txheej ntawm cov ntshav qog ntshav nce siab feem ntau thaum thawj 6 lub lim tiam ntawm kev kho mob hauv cov pab pawg lixisenatide, thiab tom qab ntawd nws zoo ib yam li cov pab pawg placebo.
Kev yoo plasma cov ntshav khov.
Hauv kev kawm tshuaj placebo nyob rau thaum xaus ntawm 24-lub lim tiam kho lub sijhawm, kev yoo ntshav cov ntshav qis los ntawm qhov pib ua tiav nrog Lixumia kho li ntawm 0.42 mmol / L txog 1.19 mmol / L.
Qib ntawm cov kua nplaum tom qab.
Kev kho mob Lixumia ua rau kom txo qis cov ntshav qab zib tom qab 2 teev tom qab sim noj mov, zoo tshaj rau cov placebo, tsis hais txog kev kho mob yooj yim.
Feem ntau, nyob rau hauv tag nrho cov kev tshawb fawb uas cov qib ntawm cov ntshav qab zib tom qab tau ntsuas, nrog Lixumia thaum kawg ntawm 24-lub lim tiam kho mob, qhov kev txo qis ntawm cov hauv paus nyob hauv thaj tsam ntawm 4.51 txog 7.96 mmol / L. Los ntawm 26,2% rau 46.8% ntawm cov neeg mob, 2-teev nyob rau qib qabzib nyob qis dua 7.8 mmol / L (140.4 mg / dl).
Lub cev hnyav.
Thaum kawg ntawm lub ntsiab kev kho mob 24 lub lis piam, Lixumia txoj kev kho nyob rau hauv kev sib xyaw nrog metformin thiab / lossis sulfonylurea hauv txhua qhov kev tswj xyuas tau ua rau muaj kev hloov pauv hauv lub cev nyhav li ntawm –1.76 kg txog .92.96 kg. Kev hloov lub cev qhov hnyav los ntawm thawj theem nyob rau hauv thaj tsam ntawm –0.38 kg mus rau –1.80 kg kuj tau pom nyob rau hauv cov neeg mob tau txais lixisenatide nyob rau hauv kev sib xyaw nrog qhov tshwj xeeb ruaj khov ntawm basal insulin, lossis hauv kev sib xyaw nrog metformin lossis sulfonylurea.
Hauv cov neeg mob uas tau pib siv cov tshuaj insulin, hauv cov pab pawg lixisenatide, lub cev qhov hnyav tseem yuav luag tsis hloov, thaum nyob hauv cov placebo pab pawg tau nce ntxiv.
Hauv cov kev tshawb fawb mus ntev ntev txog li 76 lub lis piam, qhov hnyav hnyav dua.
Kev hnyav lub cev tsis yog nyob ntawm ntau zaus ntawm xeev siab thiab ntuav.
Beta cell ua haujlwm.
Cov kev tshawb fawb soj ntsuam ntawm Lixumia qhia txhim kho beta cell muaj nuj nqi raws li ntsuas los ntawm homeostatic beta cell ua haujlwm kev ntsuas tus qauv (HOMO-β / HOMA-β).
Rov qab los ntawm thawj theem ntawm insulin secretion thiab kev txhim kho ntawm cov theem thib ob ntawm insulin secretion hauv kev teb rau kev txhaj tshuaj tiv thaiv ntshav ntawm cov ntshav qabzib tau pom tom qab ib koob tshuaj Lixumia hauv cov neeg mob uas muaj ntshav qab zib hom 2 (n = 20).
Kev soj ntsuam ntawm cov kab mob plawv.
Hauv txhua qhov kev sim tshuaj placebo hauv theem III, cov neeg mob ntshav qab zib hom 2 tsis qhia kev nce siab hauv nruab nrab lub plawv dhia.
Hauv kev kawm tshuaj placebo theem III, muaj qhov txo qis ntawm qhov nruab nrab systolic thiab diastolic ntshav siab, feem, mus txog 2.1 hli RT. Kos duab. thiab mus txog 1.5 mmHg. Kos duab.
Meta-tsom xam ntawm txhua yam ntawm nws tus kheej tsim kev mob plawv (tuag vim yog mob plawv, tsis yog ntshav tawm ntawm lub cev, tsis mob ntshav khov, pw hauv tsev kho mob vim tsis khov kho lub hlwb, pw hauv tsev kho mob vim plawv tsis ua hauj lwm thiab kho cov hlab ntshav hlab plawv) nyob rau hauv 8 qhov kev soj ntsuam ntawm III theem, uas suav nrog 2,673 cov neeg mob uas muaj ntshav qab zib hom 2 tau txais lixisenatide thiab 1,448 cov neeg mob uas tau txais cov placebo qhia txog qhov kev pheej hmoo ntawm 1.03 (95% kev ntseeg siab txog 0.64, 1.66) rau lixis Atid piv nrog cov placebo.
Tus naj npawb ntawm cov xwm txheej hauv kev soj ntsuam hauv chaw kho mob yog me me (1.9% hauv cov neeg mob tau txais lixisenatide thiab 1.8% hauv cov neeg mob tau txais cov placebo), nws tsis tso cai cia siab rau qhov kev txiav txim siab.
Qhov tshwm sim ntawm tus neeg mob plawv (lixisenatide piv rau cov placebo) yog: kev tuag vim yog mob plawv ntshav (0.3% piv nrog 0.3%), tsis mob ntshav siab-myocardial infarction (0.4% piv nrog 0.4 %), tsis mob tuag tes tuag taw (0.7% piv nrog 0.4%), pw tsev kho mob vim tsis khov kho tsis zoo (0 piv rau 0.1%), pw hauv tsev kho mob vim lub plawv tsis ua hauj lwm (0.1% piv rau 0) , mob ntsig txog hlab ntsha txhaws (0.7% tiv thaiv 1.0%).
Pharmacokinetics: Kev Zam Txim Cia.
Tom qab ua haujlwm subcutaneous rau cov neeg mob uas muaj ntshav qab zib hom 2, qhov nqus ntawm lixisenatide yog nrawm, tsis hais qhov koob tshuaj siv. Tsis hais txog ntawm koob tshuaj thiab seb lixisenatide tau siv rau hauv ib lossis ntau koob tshuaj, hauv cov neeg mob uas muaj ntshav qab zib hom 2, qhov nruab nrab tmax yog li ntawm 1 txog 3.5 teev. Hais txog kev ua haujlwm subcutaneous ntawm lixisenatide rau lub plab, ncej puab lossis xub pwg, tsis muaj qhov sib txawv hauv qhov sib txawv ntawm tus nqi ntawm kev nqus.
Kev xa Khoom.
Lixisenatide muaj kev kawm qib nruab nrab (55%) rau tib neeg cov protein.
Cov pom meej ntawm kev faib tawm tom qab subcutaneous tswj hwm ntawm lixisenatide (Vz / F) yog kwv yees li 100 L.
Biotransformation thiab excretion.
Raws li peptide, lixisenatide yog dhau los ntawm glomerular pom tom qab los ntawm tubular reabsorption thiab ntxiv cov teeb meem metabolic, uas ua rau tsim cov peptides me thiab amino acids, uas tau rov qab suav dua hauv cov protein metabolism. Tom qab tswj hwm ntawm ntau cov tshuaj nyob rau hauv cov neeg mob uas muaj ntshav qab zib hom 2, qhov nruab nrab qhov kawg kev tshem tawm ib nrab-lub neej yog kwv yees li 3 teev thiab qhov ntsuas pom meej nruab nrab (CL / F) kwv yees li 35 l / teev.
Cov Neeg Tshwj Xeeb:
Cov neeg mob uas lub raum tsis ua hauj lwm zoo.
Hauv cov neeg mob uas muaj lub raum ib txwm muaj thiab cov neeg mob uas tsis muaj lub raum lub raum ua haujlwm (tus neeg tsim muaj cov tsis muaj zog los txiav txim los ntawm cov mis Cockcroft-Gault, 50-80 ml / min), tsis muaj qhov sib txawv hauv Cmax thiab PPK ntawm lixisenatide. Hauv cov neeg mob uas muaj mob tsis ua hauj lwm lub raum (kev tsim kho lub peev xwm ntawm 30-50 ml / min), qhov ntsuas AUC (thaj tsam hauv qab txoj kab nkhaus) tau nce los ntawm 24%, thiab hauv cov neeg mob uas muaj mob raum ua kom tsis zoo (kev ua kom zoo ntawm 15-30 ml / min) - los ntawm 46 %
Cov neeg mob uas muaj lub siab ua haujlwm tsis zoo.
Txij li cov lixisenatide feem ntau yog ua kom mob raum, cov neeg mob uas mob raum los yog mob raum tsis ua haujlwm koom nrog hauv kev tshawb fawb pharmacokinetic. Hepatic kawg kuj tsis yog xav tias yuav cuam tshuam rau lub chaw muag tshuaj ntawm lixisenatide.
Paul
Tus poj niam txiv neej tsis muaj qhov tshwm sim hauv chaw kho mob uas yog lixisenatide.
Kwv Txhiaj.
Raws li cov txiaj ntsig ntawm cov kev tshawb fawb pharmacokinetic nyob rau hauv cov neeg mob Caucasian, Nyij Pooj thiab Suav, cov keeb kwm haiv neeg tsis muaj kev cuam tshuam loj hauv lub chaw muag tshuaj ntawm lixisenatide.
Cov neeg laus cov neeg mob.
Lub hnub nyoog tsis muaj kev cuam tshuam loj hauv lub tsev tshuaj pharmacokinetics ntawm lixisenatide. Hauv kev kawm pharmacokinetic nyob rau hauv cov neeg laus tsis mob ntshav qab zib, kev siv lixisenatide 20 ing hauv pawg ntawm cov neeg mob laus (11 cov neeg mob hnub nyoog 65 txog 74 xyoo thiab 7 cov neeg mob hnub nyoog ≥75 xyoo), uas ua rau muaj qhov nce nruab nrab ntawm PPC ntawm lixisenatide los ntawm 29%, piv nrog 18 cov neeg mob hnub nyoog 18 txog 45 xyoo, tej zaum muaj feem nrog kev txo qis raum kev ua haujlwm hauv pab pawg laus.
Lub cev hnyav.
Lub cev qhov hnyav tsis muaj kev cuam tshuam los ntawm kev mob loj ntawm PPK qhov taw qhia ntawm lixisenatide.

Sab Sij Huam Liksumiya

Cov lus qhia luv luv ntawm cov ntaub ntawv kev nyab xeeb.
Ntau tshaj 2,600 tus neeg mob hauv 8 qhov kev tshawb nrhiav tshuaj placebo lossis kev tshawb fawb theem III nrog kev tswj hwm tau txais Lixumia yog kev kho mob monotherapy lossis kev sib xyaw nrog metformin, sulfonylurea (nrog lossis tsis muaj metformin) lossis basal insulin (nrog lossis tsis muaj metformin lossis nrog sulfonylurea lossis tsis muaj nws).
Feem ntau cov kev phiv tshuaj pom tias tshwm sim thaum kuaj mob yog xeev ntuav, ntuav, thiab zawv plab. Cov kev tawm tsam feem ntau yog ua rau me ntsis thiab dhau los.
Kuj tseem muaj tus mob hypoglycemia (thaum Lixumia tau siv nrog sulfonylurea thiab / lossis insulin basal) thiab mob taub hau.
Kev ua xua tau pom nyob rau hauv 0.4% ntawm cov neeg mob siv Lixumia.
Hauv qab no yog cov kev phiv tshuaj uas tshwm sim nrog ntau zaus ntawm 5%, yog tias qhov ntau zaus tshwm sim ntau dua ntawm cov neeg mob uas tau txais Lixumia dua li ntawm cov neeg mob tau txais tag nrho cov tshuaj sib piv, tseem muaj cov kev tsis haum nrog ntau zaus ntawm ≥1% hauv cov neeg mob tau txais Lixumia, yog tias qhov zaus tshwm sim muaj 2 zaug ntau dua li zaus ntawm cov pawg ntawm cov neeg mob tau txais txhua qhov sib piv ntawm cov tshuaj.
Cov kev tsis zoo tshwm sim hauv cov tshuaj placebo thiab theem III kev sim nrog kev tswj hwm thaum lub sijhawm kho tag nrho (suav nrog lub sijhawm dhau ntawm lub sijhawm 24-lub lim tiam kho mob hauv kev tshawb fawb nrog ≥76 lub lis piam ntawm kev kho txhua tus).
Ntau zaus (≥1 / 10):
- hypoglycemia (ua ke nrog sulfonylurea thiab / lossis insulin hauv paus)
mob taub hau
- xeev siab, ntuav, raws plab
Feem ntau (≥1 / 100 ua ntej - khaub thuas, mob hlab pas sab saud, cystitis, kis tus kab mob)
- hypoglycemia (nrog metformin tshwj xeeb)
- kiv taub hau, pw tsaug zog
- dyspepsia
- mob nraub qaum
- khaus ntawm qhov chaw txhaj tshuaj
Ua tsis raws txoj cai (≥1 / 1000 txog - qhov tshuaj tiv thaiv anaphylactic)
- urticaria

Kev piav qhia ntawm tus neeg qhov tsis zoo:
Kev ntshav siab.
Hauv cov neeg mob noj Lixumia raws li kev kho mob monotherapy, tsos mob hypoglycemia tshwm sim hauv 1.7% ntawm cov neeg mob tau txais lixisenatide, thiab hauv 1.6% ntawm cov neeg mob tau txais placebo. Thaum Lixumia tau siv nyob rau hauv kev sib xyaw ua ke nrog metformin thaum lub sijhawm kev kho mob tag nrho, tus mob hypoglycemia tshwm sim hauv 7.0% ntawm cov neeg mob tau txais lixisenatide thiab 4.8% ntawm cov neeg mob tau txais cov placebo.
Hauv cov neeg mob noj Lixumia ua ke nrog sulfonylurea thiab metformin, cov tsos mob hypoglycemia tshwm sim hauv 22.0% ntawm cov neeg mob tau txais lixisenatide thiab 18.4% ntawm cov neeg mob tau txais placebo (3.6% txog qhov sib txawv) thaum lub sijhawm kho tag nrho. Thaum Lixumia tau siv nrog kev sib xyaw nrog basal insulin nrog lossis tsis muaj metformin thaum lub sijhawm kho mob tag nrho, cov tsos mob hypoglycemia tshwm sim hauv 42.1% ntawm cov neeg mob kho nrog lixisenatide thiab hauv 38.9% ntawm cov neeg uas tau txais placebo (3.2% ntawm qhov tsis sib txawv).
Thaum Lixumia tau siv nyob rau hauv kev sib xyaw tshwj xeeb nrog sulfonylurea thaum lub sijhawm kev kho mob tag nrho, cov tsos mob hypoglycemia tshwm sim hauv 22.7% ntawm cov neeg mob tau txais lixisenatide, piv nrog 15.2% tau txais cov placebo (7.5% tsis txawv). Thaum Lixumia tau siv los ua ke nrog sulfonylurea thiab basal insulin, tsos mob hypoglycemia tshwm sim hauv 47.2% ntawm cov neeg mob tau txais lixisenatide piv nrog 21.6% tau txais cov placebo (25.6% ntawm qhov sib txawv).
Feem ntau, nyob rau tag nrho lub sijhawm kho nyob rau hauv cov tshuaj placebo tshuaj sim theem III, qhov tshwm sim ntawm cov tsos mob hnyav uas ua rau nws muaj ntshav tsis txaus (0.4% hauv cov neeg mob tau txais lixisenatide thiab 0.2% hauv cov neeg mob tau txais placebo).
Kev ua txhaum ntawm lub plab zom mov.
Lub sijhawm nyob hauv 24-lub lim tiam ntawm kev kho mob, xeev siab thiab ntuav yog cov tsos mob tshwm sim ntau tshaj plaws. Kev tshwm sim ntawm kev xeev siab tau ntau dua nyob rau hauv cov pab pawg lixisenatide (26.1%) piv rau cov pab pawg placebo (6.2%), thiab kev ntuav ntuav yog siab dua nyob rau hauv cov pab pawg lixisenatide (10.5%) piv rau cov pab pawg placebo (1.8 %).
Qhov kev tshua tshwm sim feem ntau me me thiab hloov thiab tshwm sim hauv thawj 3 lub lis piam tom qab pib kho. Tom qab, nyob rau lub lim tiam tom ntej, qhov ntau zaus maj mam poob.
Cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj.
Lub sijhawm 24 lub lis piam kho mob tseem ceeb, cov tshuaj tiv thaiv nyob rau ntawm qhov chaw txhaj tshuaj tau pom nyob rau hauv 3.9% ntawm cov neeg mob tau txais Lixumia, thiab cov tshuaj tiv thaiv nyob ntawm qhov chaw txhaj tshuaj kuj tseem pom nyob hauv 1.4% ntawm cov neeg mob tau txais cov placebo.
Feem ntau cov tshuaj tiv thaiv tau mob me me thiab feem ntau tsis cheem kev kho mob.
Kev Siv Tshuaj Tiv Thaiv
Vim tias qhov tshuaj tiv thaiv kab mob muaj peev xwm ntawm cov tshuaj uas muaj cov protein lossis peptides, tom qab kho nrog Lixumia, cov neeg mob tuaj yeem tsim cov tshuaj tiv thaiv kab mob rau lixisenatide, thiab thaum kawg ntawm lub sijhawm 24 lub lis piam kev kho mob hauv cov tshuaj placebo hauv 69.8% ntawm cov neeg mob tau txais lixisenatide, cov xwm txheej tshuaj tiv thaiv zoo tau tsim. Thaum kawg ntawm tag nrho 76 lub lis piam kev kho mob sijhawm, feem pua ntawm cov neeg mob seropositive tau zoo sib xws. Qhov kawg ntawm lub ntsiab kev kho mob 24-lub lim tiam, hauv 32.2% ntawm cov neeg mob uas muaj cov tshuaj tiv thaiv zoo, qhov tshuaj tiv thaiv kab mob tau siab tshaj qhov qis tshaj ntawm kev txiav txim siab, thiab qhov kawg ntawm tag nrho 76 lub lis piam lub sijhawm kho mob hauv 44.7% ntawm cov neeg mob, cov tshuaj tiv thaiv kab mob tau siab tshaj qhov txwv qis ntawm kev txiav txim siab Cov. Tom qab kev txiav tawm ntawm kev kho mob, kev soj ntsuam ntawm ntau tus neeg mob seropositive txuas ntxiv, tsis pub dhau 3 lub hlis feem pua tau nqis mus txog kwv yees li 90%, thiab tom qab 6 lub hlis lossis ntau dua - txog 30%.
Cov kev hloov hauv HbA1c los ntawm qhov pib yog qhov zoo sib xws tsis hais txog qhov xwm txheej ntawm lub cev (zoo lossis tsis zoo).
Ntawm cov neeg mob HbA1c ntsuas uas tau txais lixisenatide, 79.3% muaj cov tshuaj tiv thaiv tsis zoo lossis cov tshuaj tiv thaiv tsis haum yog qhov tsawg dua qhov kev txwv qis, thiab qhov seem 20.7% ntawm cov neeg mob tau muaj cov tshuaj tiv thaiv kab mob.Hauv pawg neeg mob ntawm cov neeg mob (5.2%) nrog cov tshuaj tiv thaiv kab mob siab tshaj plaws, qhov nruab nrab HbA1c kev txhim kho ntawm lub limtiam 24 thiab lub limtiam 76 tau nyob hauv qhov chaw ntsuas tseem ceeb, txawm li cas los xij, muaj kev hloov pauv ntawm glycemic, thiab 1.9% tsis muaj tsawg dua HbA1c.
Cov xwm txheej ntawm cov tshuaj tiv thaiv (tsis zoo lossis tsis zoo) tsis tso cai twv seb qhov txo qis HbA1c hauv ib tus neeg mob.
Tsis muaj qhov sib txawv ntawm daim ntawv qhia txog kev nyab xeeb tag nrho hauv cov neeg mob, tsis hais txog lub cev tiv thaiv kab mob, tshwj tsis yog muaj qhov tshwm sim ntau ntxiv ntawm cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj (dhau tag nrho lub sijhawm kho, 4,7% hauv cov neeg mob uas muaj qhov tshuaj tiv thaiv zoo, piv rau 2.5% hauv cov neeg mob seronegative). Feem ntau cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj yog qhov mob me, tsis hais txog qhov xwm txheej twg.
Tsis muaj tus ntoo khaub lig-reactivity piv rau ib txwm glucagon lossis endogenous GLP-1.
Kev ua xua tsis haum.
Hauv lub sijhawm 24 lub lis piam kev kho mob, kev fab tshuaj muaj feem cuam tshuam nrog lixisenatide (xws li tshuaj tiv thaiv anaphylactic, angioedema, thiab urticaria) pom nyob rau 0.4% ntawm cov neeg mob kho nrog lixisenatide, thaum muaj peev xwm ua xua tshwm sim tsawg dua hauv 0.1% ntawm cov neeg mob tau txais cov placebo.
Anaphylactic cov tshuaj tiv thaiv tau tsim hauv 0.2% ntawm cov neeg mob tau txais lixisenatide, piv nrog kev tsis muaj tshuaj nyob rau hauv cov placebo pawg.
Feem ntau ntawm qhov tsim kev fab tshuaj tsis haum muaj mob me heev. Ib qhov teeb meem ntawm anaphylactoid cov tshuaj tiv thaiv tau tsim thaum lub sijhawm sim tshuaj kho mob lixisenatide.
Lub plawv dhia.
Hauv cov kev tshawb fawb txog cov neeg ua haujlwm pab dawb noj qab haus huv, qhov nce siab ntawm lub plawv dhia tau pom tom qab kev tswj hwm 20 μg ntawm lixisenatide. Mob plawv dhia tsis xwm yeem, tshwj xeeb, tachycardia (0.8% piv nrog kev tshem tawm yeeb tshuaj.
Lub sijhawm 24 lub lim tiam ntawm kev kho mob, qhov xwm txheej ntawm kev tsis ua tiav vim yog qhov tshwm sim tsis zoo yog 7.4% hauv Lixumia pawg piv nrog 3.2% hauv cov pawg placebo. Feem ntau cov kev mob tshwm sim uas ua rau tsis pom kev kho nyob rau hauv cov pab pawg lixisenatide yog xeev siab (3.1%) thiab ntuav (1.2%).
Ceeb toom qhia tsam tsis haum tshuaj.
Nws yog ib qho tseem ceeb uas yuav tau qhia qhov kev xav tias muaj kev phiv tshuaj tom qab tso npe tshuaj. Qhov no tso cai rau koj soj ntsuam xyuas kev tshuav nyiaj li cas ntawm txiaj ntsig / kev pheej hmoo ntawm cov tshuaj. Cov neeg ua haujlwm noj qab haus huv raug thov kom ceeb toom txhua qhov kev xav tias muaj kev cuam tshuam zoo los ntawm kev qhia thoob tebchaws.

Tsis muaj kev paub txog kev kho mob nrog kev siv lixisenatide rau cov neeg mob uas muaj ntshav qab zib hom 1; nws yuav tsum tsis txhob siv rau hauv cov neeg mob no.
Lixisenatide yuav tsum tsis txhob siv los kho tus kab mob ntshav qab zib ketoacidosis.
Mob ncauj mob taub hau.
Kev siv cov glucagon-zoo li peptide-1 receptor agonists (GLP-1) tau cuam tshuam nrog kev pheej hmoo ntawm kev tsim mob pancreatitis.
Muaj ntau yam xwm txheej ntawm tus mob lees ua tus kab mob pancreatitis tau qhia nrog kev siv lixisenatide, txawm hais tias ib qho kev sib raug zoo tsis tseem ceeb.
Nws yog ib qho tsim nyog yuav tsum tau qhia rau cov neeg mob txog cov tsos mob tshwm sim ntawm tus mob huam tiaj: mob pheej, mob plab heev. Yog hais tias pom muaj tus kab mob pancreatitis, nws yog ib qho tsim nyog kom tsum tsis txhob siv lixisenatide, yog tias pom tseeb tias mob pancreatitis, kev siv lixisenatide yuav tsum tsis txhob rov qab siv dua. Kev ceev faj yuav tsum tau siv thaum siv rau hauv cov neeg mob tom qab pancreatitis.
Kev mob hnyav rau lub plab zom mov.
Kev siv cov agonists ntawm GLP-1 receptors tuaj yeem cuam tshuam nrog kev phiv tshuaj los ntawm cov hnyuv.
Lixisenatide tsis tau kawm txog cov neeg mob uas mob plab hnyuv, suav nrog mob nyhav, thiab vim li no, kev siv lixisenatide tsis pom zoo.
Lub raum khiav tsis zoo.
Tsuas muaj kev kho mob tsawg rau cov neeg mob uas tsis tshua ua kom lub raum tsis ua haujlwm (kev tsim kho lub peev xwm tshem tau 30-50 ml / min), thiab tsis muaj kev kho mob rau cov neeg mob uas muaj lub siab tsis zoo ua tsis taus (ua kom tsis muaj ntshav tsawg dua 30 ml / min) lossis hauv cov neeg mob hauv lub davhlau ya nyob twg ntawm tus kab mob. ob lub raum. Hauv cov neeg mob uas muaj mob raum khiav tsis zoo, Lixumia yuav tsum siv nrog ceev faj. Hauv cov neeg mob uas muaj lub raum tsis ua haujlwm zoo lossis hauv cov neeg mob hauv lub davhlau ya nyob twg ntawm kev mob raum, kev siv tsis pom zoo (saib "Dosage and Administration" thiab "Pharmacokinetics").
Kev ntshav siab.
Cov neeg mob uas tau txais Lixumia nrog sulfonylurea lossis insulin basal yuav muaj kev pheej hmoo hauv lub siab ntshav qab zib kom tsawg. Txhawm kom txo cov ntshav qog ntshav qab zib, nws tuaj yeem txo qhov koob tshuaj sulfonylurea lossis basal insulin (saib "Dosage and Administration"). Lixumia yuav tsum tsis txhob siv nrog cov tshuaj insulin basal thiab sulfonylurea vim qhov muaj feem yuav ua rau tus mob ntshav qab zib tsawg.
Yooj Yim Tshuaj Kho Mob
Kev maj mam khiav tawm ntawm lub plab zom mov nrog kev siv lixisenatide tuaj yeem txo tus nqi nqus ntawm cov tshuaj noj ntawm qhov ncauj. Hauv cov neeg mob uas tau txais cov tshuaj noj qhov ncauj uas yuav tsum muaj kev nqus tau sai, kev soj ntsuam, lossis tshuaj muaj qhov nqaim kho qis, Lixumia yuav tsum siv nrog ceev faj. Cov lus qhia tshwj xeeb hais txog kev siv cov tshuaj no raug muab hauv nqe “Kev Sib Tham Nrog Tshuaj”.
Cov neeg tsis tau npaj tseg.
Lixisenatide tsis tau kawm txog kev txuam nrog dipeptidyl peptidase-4 (DPP-4) cov tshuaj tiv thaiv kab mob.
Tsuas muaj kev paub tsawg hauv cov neeg mob uas muaj lub plawv tsis ua hauj lwm hnyav.
Lub cev qhuav dej.
Cov neeg mob uas tau txais kev kho mob nrog Lixumia yuav tsum qhia txog kev pheej hmoo ntawm lub cev qhuav dej vim muaj kev phiv los ntawm lub plab zom mov thiab ceev faj kom tsis txhob hypovolemia.
Tshwjxeeb.
Cov tshuaj muaj metacresol, uas tuaj yeem ua rau muaj kev tsis haum.
Cov poj niam muaj hnub nyoog yug menyuam.
Lixumia tsis pom zoo rau cov poj niam ntawm lub hnub nyoog yug menyuam uas tsis siv tshuaj txwv.
Cev xeeb tub
Muaj cov ntaub ntawv tsis txaus ntawm kev siv Lixumia hauv cov poj niam cev xeeb tub. Kev kawm ua ntej pom tau hais tias muaj tshuaj lom deev.
Peb paub tsis meej tias yuav muaj xwm txheej dabtsi rau tib neeg.
Lixumia yuav tsum tsis txhob siv thaum cev xeeb tub. Hloov, insulin yog qhov pom zoo.
Yog tias tus neeg mob xav ua lub cev xeeb tub los yog cev xeeb tub tau tshwm sim, kev kho mob nrog Lixumia yuav tsum tsis ua mus ntxiv.
Lactation.
Kuj tsis paub meej tias Lixumia puas kis tau tib neeg cov kua mis. Lixumia yuav tsum tsis txhob siv thaum lactation.
Cuam Tshuam.
Kev kawm ua ntej tsis tau qhia paub hais tias muaj kev phom sij txog kev muaj tub muaj ki.
Cov yam ntxwv ntawm cov nyhuv ntawm cov tshuaj ntawm lub peev xwm tsav lub tsheb lossis cov phom sij phom sij.
Lyskumia tsis cuam tshuam lossis cuam tshuam rau qhov muaj peev xwm ntawm kev tsav lub tsheb lossis tshuab. Thaum noj nrog kev sib xyaw nrog sulfonylurea lossis basal insulin, cov neeg mob yuav tsum raug qhia kom ceev faj kom tsis txhob mob ntshav qab zib thaum tsav tsheb lossis siv cov tshuab.

Cia rau cov neeg mob.
Khaws ntawm qhov kub ntawm 2 degrees C rau 8 degrees C hauv qhov chaw tsaus. Tsis khov. Txav deb ntawm lub taub yees txias.
Tom qab siv thawj zaug, rab koob xaum qhuav siv tau rau 14 hnub ntawm qhov kub tsis tshaj li 30 degrees C. Tsis khov.
Khaws tsis ncav cuag ntawm cov menyuam yaus.

Cov lus qhia rau kev siv syringe cwj mem Lixumia
Ua ntej siv Lixumia koob txhaj tshuaj, ua tib zoo nyeem cov lus qhia.
Khaws cov lus qhia kho mob no rau kev siv kho mob rau kev siv yav tom ntej.
Lixumia yog ib qho xaum xaum xaum tso dej rau txhaj uas muaj 14 koob. Txhua koob tshuaj muaj 10 μg lossis 20 μg ntawm lixisenatide hauv 0.2 ml.
• Ua ib qho kev txhaj tshuaj ib hnub twg xwb.
• Txhua Lixumium syringe mem muaj 14 koob tshuaj ua ntej. Tsis tas txhaj ib qho tshuaj.
• Ua ntej siv cov xaum xaum, sab laj rau koj tus kws kho mob txog kev siv tshuaj.
• Yog tias nws ua tsis tau kiag li los ua raws li cov lus qhia koj tus kheej, lossis koj tsis tuaj yeem nqa tus xaum xaum hluav taws xob (piv txwv, yog tias koj muaj teeb meem tsis pom kev), siv sab nraud pab.
• Tus cwj mem no yog rau ib leeg nkaus xwb. Sib koom txwv tsis pub ua.
• Nco ntsoov xyuas cov ntawv cim kom paub meej tias cov tshuaj Lixumia koob txhaj tshuaj tsis sib xyaw. Kuj kuaj xyuas cov chaw sib pauv uas tsis dhau sijhawm.
Siv cov tshuaj tsis raug cai tuaj yeem tsim kev puas tsuaj.
• Tsis txhob sim tso kua tawm ntawm lub taub hau ntawv uas siv lub koob txhaj tshuaj. Cov Ntaub Ntawv Koob (yeem)
• Tsuas siv cov koob uas tau pom zoo siv nrog Lixumia. Siv cov koob uas siv pov tseg txij li 29 mus rau 32 hauv Lixumia koob txhaj tshuaj. Nws yuav zoo dua yog tias koj nug koj tus kws kho mob txog qhov ntev thiab ntsuas ntawm rab koob.
• Yog tias txhaj tshuaj nrog kev pab sab nraud, yuav tsum tau saib xyuas kom tsis txhob ua rau lwm tus raug mob rab koob. Txwv tsis pub, kis tau tus mob yog kis tau.
• Rau txhua txoj kev txhaj tshuaj, siv cov koob tshiab los tiv thaiv Lixumia kev sib kis thiab kev tuaj yeem tau.

Kev taw qhia ntawm cov tshuaj Lixumia

Hom 2 mob ntshav qab zib mellitus rau cov neeg laus kom tau txais glycemic tswj nyob rau hauv cov neeg mob uas mob ntshav qab zib mellitus tsis tswj hwm los ntawm kev kho ntshav qab zib tas mus li.

Lixumia yog qhia ua ke nrog cov tshuaj hauv qab no hauv qhov ncauj hypoglycemic:

metformin
ib qho tshuaj hypoglycemic qhov ncauj ntawm sulfonylurea pawg,
kev sib xyaw ntawm cov tshuaj no.

Lixumia yog qhia nrog cov kua dej hauv paus:

nyob rau hauv monotherapy,
xyaw nrog metformin,
muaj kev sib xyaw nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg.

ICD-10 cov lis dej num

ICD-10 code	Kev taw qhia
E11	Mob ntshav qab zib Hom 2

Kev noj tshuaj ntxiv

Thawj koob tshuaj yog 10 micrograms ntawm Lixumia ib hnub ib zaug rau 14 hnub.

Tom qab ntawd cov koob tshuaj Lixumia yuav tsum nce ntxiv rau 20 mcg ib hnub ib zaug. Cov koob tshuaj no yog txhawb nqa.

Thaum Lixumia ntxiv rau qhov kev kho mob metformin uas twb muaj lawm, Metformin tuaj yeem txuas ntxiv yam uas tsis tas hloov cov tshuaj.

Thaum Lixumia ntxiv rau qhov kev kho mob uas twb muaj lawm nrog tshuaj ntawm qhov ncauj hypoglycemic ntawm sulfonylurea pawg lossis los ua ke nrog cov tshuaj ntawm qhov ncauj ntawm sulfonylurea pawg thiab insulin basal, txhawm rau txo qis kev pheej hmoo ntawm hypoglycemia, koj tuaj yeem txiav txim siab txo qhov tshuaj ntawm qhov ncauj hypoglycemic tshuaj ntawm sulfonylurea pab pawg lossis basal insulin. Cov lus qhia tshwj xeeb ").

Kev siv cov tshuaj Lixumia tsis tas yuav tsum tau saib xyuas tshwj xeeb ntawm kev saib xyuas cov kua nplaum hauv cov ntshav. Txawm li cas los xij, thaum siv los ua ke nrog kev noj tshuaj ntawm qhov ncauj ntawm sulfonylurea pawg lossis basal insulin, tshuaj xyuas cov ntshav qabzib concentration lossis kev tswj tus kheej (tswj hwm los ntawm tus neeg mob) ntawm cov ntshav qabzib concentration yuav tsum tau kho qhov tshuaj ntawm qhov ncauj hypoglycemic tshuaj ntawm sulfonylurea pawg lossis basal insulin.

Cov pab pawg neeg tshwj xeeb

Cov menyuam yaus thiab hnub nyoog qis dua 18 xyoo

Tam sim no, kev nyab xeeb thiab ua haujlwm ntawm cov tshuaj Lixumia hauv cov neeg mob uas muaj hnub nyoog qis dua 18 xyoo tsis tau kawm.

Neeg laus

Tsis tas yuav txhaj koob tshuaj nyob ntawm tus neeg mob lub hnub nyoog.

Cov neeg mob mob siab tsis ua haujlwm

Cov neeg mob lub siab tsis ua hauj lwm yuav tau kho kom haum.

Cov neeg mob raum tsis ua haujlwm

Kev hloov tshuaj tsis tas yuav tsum muaj nyob rau hauv cov neeg mob uas mob raum tsis zoo (creatinine tshem tawm 50-80 ml / min) thiab mob raum tsis ua haujlwm (creatinine tshem tawm 30-50 ml / min).

Tsis muaj kev paub txog kev kho mob nrog kev siv Lixumia hauv cov neeg mob uas lub raum tsis ua haujlwm loj (kev tsim muaj peev xwm ua kom tsawg dua 30 ml / min) lossis nrog rau kev mob raum tsis ua haujlwm, thiab yog li ntawd kev siv Lixumia hauv pawg neeg mob no yog sib kis.

Cov tshuaj Lixumia muab rau noj 1 zaug nyob rau ib hnub nyob rau hauv 1 teev ua ntej noj mov thawj hnub lossis tsis pub dhau 1 teev ua ntej noj hmo. Yog tias cov koob tshuaj ntxiv hla, nws yuav tsum raug tswj ua ntej 1 teev ua ntej noj mov tom ntej. Cov tshuaj Lixumia yog muab tshuaj subcutaneously hauv tus ncej puab, plab phab ntsa lossis xub pwg. Cov tshuaj Lixumia tsis tuaj yeem muab tshuaj rau hauv qhov quav thiab tshuaj intramuscularly. Ua ntej siv, Lixumia koob txhaj tshuaj yuav tsum tau muab cia rau hauv tub yees ntawm qhov kub ntawm 2-8 ° C hauv nws cov khoom ntim kom tiv thaiv nws los ntawm kev nphav raug. Tom qab siv thawj zaug, Lixumia syringe mem yuav tsum khaws cia ntawm qhov kub tsis tshaj 30 ° C. Tom qab siv txhua lub sijhawm, Lixumium koob txhaj tshuaj yuav tsum tau kaw nrog lub hau kom tiv thaiv nws kom tsis txhob raug rau lub teeb. Lub Lixumia Syringe Cwj mem yuav tsum tsis txhob cia nrog rab koob txuas nrog. Tsis txhob siv Lixumia lub koob txhaj tshuaj yog tias nws tau khov.

Tus Lixumia Syringe Cwj mem yuav tsum muab pov tseg tom qab 14 hnub.

Sab sij huam

Qhov ntau zaus ntawm cov kev mob tshwm sim (HP) tau txiav txim siab raws li hauv qab no: feem ntau: ≥10%, feem ntau: ≥1% - 76 lub lis piam) tshwm sim nrog zaus ntawm> 5% (yog tias lawv cov ntau zaus hauv cov neeg mob noj Lixumia piv nrog cov neeg mob noj tag nrho lwm cov tshuaj sib piv, suav nrog cov placebo), nrog rau zaus ntawm> 1% hauv cov neeg mob hauv pab pawg Lixumia, yog tias lawv cov zaus ntau dua 2 zaug ntawm tus mob HP hauv cov neeg mob tau txais ib qho ntawm cov tshuaj sib piv (suav nrog cov placebo) Cov.

Kis tau thiab kis kab mob

Tus mob khaub thuas, mob ntsws ua pa.

Kev ntshaib plab thiab zaub mov kev ntshawv siab

Kev mob ntshav qab zib yog tshwm sim nrog cov tsos mob hauv chaw kuaj mob (thaum Lixumia yog siv ua ke nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pab pawg thiab / lossis insulin basal).

Kev tsis taus ntawm lub paj hlwb

Lub plab zom mov tsis zoo

Xeev siab, ntuav, raws plab.

Musculoskeletal thiab sib txuas ntawm cov nqaij mos tsis zoo

Hauv cov neeg mob uas tau txais Lixumia hauv kev kho mob monotherapy lossis hauv kev sib xyaw nrog metformin, hypoglycemia nrog cov kev mob tshwm sim tau tshwm sim ntau zaus, thiab nws cov zaus hauv cov neeg mob uas tau txais Lixumia zoo ib yam li cov placebo thaum lub sijhawm kho tag nrho.

Hauv cov neeg mob uas tau txhaj nrog Lixumia hauv kev sib xyaw nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg lossis basal insulin, qhov tshwm sim ntawm hypoglycemia tshwm sim nrog cov tsos mob hauv tsev kho mob tau tshwm sim heev.

Thaum lub sijhawm tag nrho ntawm kev kho mob nrog Lixumia, qhov tshwm sim ntawm kev mob ntshav qab zib uas tshwm sim nrog cov tsos mob hauv tsev kho mob tau nce siab dua me ntsis nrog cov placebo, thaum Lixumia tau siv ua ke:

nrog rau qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg thiab metformin,
nrog lub hauv paus insulin monotherapy,
nrog kev sib xyaw ntawm basal insulin thiab metformin.

Nyob rau lub sijhawm kev kho mob tag nrho, thaum Lixumia tau siv nrog kev kho mob monotherapy nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg, hypoglycemia nrog cov kev mob tshwm sim hauv 22.7% ntawm cov neeg mob kho nrog Lixumia thiab hauv 15,2% ntawm cov neeg mob uas tau txais placebo.Thaum Lixumia tau siv nyob rau hauv peb zaug ua ke nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg thiab basal insulin, hypoglycemia nrog cov kev mob tshwm sim hauv 47.2% ntawm cov neeg mob kho nrog lixisenatide, thiab hauv 21.6% ntawm cov neeg mob kho nrog placebo.

Feem ntau, nyob rau tag nrho lub sijhawm ntawm kev siv tshuaj hauv cov tswj sim theem III, kev tshwm sim muaj ntshav nce siab ntau nrog cov kev soj ntsuam mob sib haum rau qhov kev sau "tsis raug" (hauv 0.4% hauv cov neeg mob tau txais Lixumia thiab hauv 0.2% hauv cov neeg mob uas tau txais cov placebo) Cov.

Lub plab zom mov tsis zoo

Xeev siab thiab ntuav yog feem ntau mob HP thaum lub sijhawm 24-lub lim tiam ntawm kev kho mob. Qhov tshwm sim ntawm kev xeev siab tau ntau dua hauv cov neeg mob kho nrog Lixumia (26.1%) dua li hauv cov neeg mob kho nrog placebo (6.2%). Qhov tshwm sim ntawm ntuav tseem muaj ntau dua hauv cov neeg mob kho nrog Lixumia (10.5%) dua li hauv cov neeg mob kho nrog placebo (1.8%). Cov HPs feem ntau me me thiab hloov thiab tshwm sim hauv thawj 3 lub lis piam tom qab pib kho mob. Tom ntej lub lim piam tom ntej, lawv maj mam poob.

Hauv cov neeg mob kho nrog Lixumia, qhov tshwm sim ntawm xeev siab yog qis dua (24.5%) dua li cov neeg mob kho nrog exenatide 2 zaug hauv ib hnub (35,1%), thiab ntau zaus ntawm lwm cov HP los ntawm kev mob plab hauv ob qho tib si kev kho mob pab pawg tau zoo ib yam.

Cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj

Cov tshuaj tiv thaiv nyob ntawm qhov chaw txhaj tshuaj thaum 24-lub lim tiam kev kho mob tau pom nyob rau hauv 3.9% ntawm cov neeg mob tau txais Lixumia, thaum nyob hauv cov neeg mob tau txais cov placebo, lawv tau pom nrog ntau zaus ntawm 1.4%. Feem ntau cov tshuaj tiv thaiv tau mob me me thiab feem ntau tsis cheem kev kho mob.

Vim tias qhov tshuaj tiv thaiv kab mob muaj peev xwm ntawm cov tshuaj uas muaj cov protein lossis peptides, tom qab kev kho mob nrog Lixumia hauv cov neeg mob, kev tsim cov tshuaj tiv thaiv rau lixisenatide yog ua tau. Thaum kawg ntawm lub sijhawm 24-lub lim tiam kho mob, hauv kev soj ntsuam cov tshuaj placebo, 69.4% ntawm cov neeg mob kho nrog lixisenatide muaj cov txiaj ntsig zoo rau kev muaj cov tshuaj tiv thaiv kab mob rau lixisenatide. Txawm li cas los xij, kev hloov pauv ntawm HbA 1c Performance index, piv nrog tias ua ntej kev siv lixisenatide, zoo ib yam, tsis hais txog qhov zoo lossis qhov tshwm sim ntawm kev soj ntsuam rau qhov muaj cov tshuaj tiv thaiv rau lixisenatide. Ntawm cov neeg mob kho nrog lixisenatide uas muaj HbA 1c tus qhab nia, 79.3% muaj qhov tsis zoo rau cov tshuaj tiv thaiv kab mob rau lixisenatide lossis titer ntawm cov tshuaj tiv thaiv mus rau lixisenatide yog qis dua qis qis rau nws qhov ntau, thaum tshuav 20.7% ntawm cov neeg mob tau kom muaj nuj nqis ntau ntawm cov tshuaj tiv thaiv rau lixisenatide.

Tsis muaj qhov sib txawv ntawm daim ntawv qhia txog kev nyab xeeb tag nrho hauv cov neeg mob nyob ntawm cov xwm txheej ntawm cov tshuaj tiv thaiv kab mob rau lixisenatide, tshwj tsis yog muaj qhov nce ntxiv ntawm cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj hauv cov neeg mob tiv thaiv kab mob. Feem ntau qhov tshwm sim ntawm qhov chaw txhaj tshuaj tau mob me me, tsis hais lub sijhawm lossis tsis muaj cov tshuaj tiv thaiv rau lixisenatide.

Muaj tsis muaj tus ntoo khaub lig-immunological reactivity nrog haiv neeg glucagon los yog endogenous GLP-1.

Kev tsis haum tshuaj muaj feem cuam tshuam nrog kev siv lixisenatide (xws li kev siv tshuaj anaphylactic, angioedema thiab urticaria) thaum lub sijhawm 24-lub lim tiam kho tau pom nyob rau 0.4% ntawm cov neeg mob kho nrog Lixumia, piv nrog tsawg dua 0.1% ntawm cov neeg mob hauv pawg placebo.

Ua ntej lub sijhawm txiav tawm ntawm cov tshuaj no

Kev nquag tsis noj tshuaj ntxiv vim tias qhov tshwm sim tsis zoo yog 7.4% hauv Lixumia pawg thiab 3.2% hauv pawg placebo. Cov neeg mob HPs feem ntau ua rau tshem tawm kev kho mob hauv pawg Lixumia yog xeev siab (3.1%) thiab ntuav (1.2%).

Dosage daim ntawv

Kev daws rau kev txhaj tshuaj 0.05 mg / ml thiab 0.1 mg / ml

1 ml ntawm cov tshuaj muaj:

cov tshuaj ua kom nquag plias - lixisenatide 0.05 mg lossis 0.10 mg

kev zam: 85% glycerin, sodium acetate trihydrate, L-methionine, metacresol, hydrochloric acid, sodium hydroxide, dej rau kev txhaj tshuaj.

Pob tshab tsis muaj xim ua kua.

Cov chaw muag tshuaj

Tom qab ua haujlwm subcutaneous rau cov neeg mob uas muaj ntshav qab zib hom 2, qhov nqus ntawm lixisenatide yog nrawm, tsis hais qhov koob tshuaj siv. Tsis hais txog ntawm koob tshuaj thiab seb lixisenatide tau siv rau hauv ib lossis ntau koob tshuaj, hauv cov neeg mob uas muaj ntshav qab zib hom 2, qhov nruab nrab tmax yog li ntawm 1 txog 3.5 teev. Hais txog kev ua haujlwm subcutaneous ntawm lixisenatide rau lub plab, ncej puab lossis xub pwg, tsis muaj qhov sib txawv hauv qhov sib txawv ntawm tus nqi ntawm kev nqus.

Lixisenatide muaj kev kawm qib nruab nrab (55%) rau tib neeg cov protein.

Cov pom meej ntawm kev faib tawm tom qab subcutaneous tswj hwm ntawm lixisenatide (Vz / F) yog kwv yees li 100 L.

Biotransformation thiab excretion

Raws li peptide, lixisenatide yog dhau los ntawm glomerular pom tom qab los ntawm tubular reabsorption thiab ntxiv cov teeb meem metabolic, uas ua rau tsim cov peptides me thiab amino acids, uas tau rov qab suav dua hauv cov protein metabolism.

Tom qab tswj hwm ntawm ntau cov tshuaj nyob rau hauv cov neeg mob uas muaj ntshav qab zib hom 2, qhov nruab nrab qhov kawg kev tshem tawm ib nrab-lub neej yog kwv yees li 3 teev thiab qhov ntsuas pom meej nruab nrab (CL / F) kwv yees li 35 l / teev.

Cov neeg mob uas lub raum tsis ua hauj lwm zoo

Hauv cov neeg mob uas muaj hnub nyoog me (creatinine tshem tawm tau txiav txim los ntawm tus qauv Cockcroft-Gault, yog 60-90 ml / min), muaj pes tsawg (creatinine tshem tau yog 30-60 ml / min) thiab mob tsis zoo rau lub raum (creatinine tshem yog 15-30 ml / min) min), AUC (thaj chaw hauv qhov kev tsom xam piv rau lub sijhawm nkhaus) nce ntxiv 46%, 51% thiab 87%, xwm yeem.

Cov neeg mob uas muaj lub siab ua haujlwm tsis zoo

Txij li cov lixisenatide feem ntau yog ua kom mob raum, cov neeg mob uas mob raum los yog mob raum tsis ua haujlwm koom nrog hauv kev tshawb fawb pharmacokinetic. Hepatic kawg kuj tsis yog xav tias yuav cuam tshuam rau lub chaw muag tshuaj ntawm lixisenatide.

Tus poj niam txiv neej tsis muaj qhov tshwm sim hauv chaw kho mob uas yog lixisenatide.

Raws li cov txiaj ntsig ntawm cov kev tshawb fawb pharmacokinetic nyob rau hauv cov neeg mob Caucasian, Nyij Pooj thiab Suav, cov keeb kwm haiv neeg tsis muaj kev cuam tshuam loj hauv lub chaw muag tshuaj ntawm lixisenatide.

Lub hnub nyoog tsis muaj kev cuam tshuam loj hauv lub tsev tshuaj pharmacokinetics ntawm lixisenatide. Hauv kev kawm pharmacokinetic nyob rau hauv cov neeg laus tsis mob ntshav qab zib, kev siv lixisenatide 20 ing hauv pawg ntawm cov neeg mob laus (11 cov neeg mob hnub nyoog 65 txog 74 xyoo thiab 7 cov neeg mob hnub nyoog ≥ 75 xyoo), uas ua rau muaj qhov nruab nrab nce ntxiv ntawm PPK ntawm lixisenatide los ntawm 29%, piv nrog 18 cov neeg mob hnub nyoog 18 txog 45 xyoo, tej zaum muaj feem nrog kev txo qis raum kev ua haujlwm hauv pab pawg laus.

Lub cev qhov hnyav tsis muaj kev cuam tshuam los ntawm kev mob loj ntawm PPK qhov taw qhia ntawm lixisenatide.

Cov txiaj ntsig ntawm lixisenatide yog kev sib kho los ntawm kev sib cuam tshuam tshwj xeeb nrog cov receptors GLP-1, uas ua rau muaj kev nce ntxiv ntawm intracellular cyclic adenosine monophosphate (cAMP). Lixisenatide stimulates insulin secretion thaum cov ntshav qab zib cov ntshav nce siab, tab sis tsis nrog normoglycemia, uas ua rau muaj kev pheej hmoo ntawm hypoglycemia.

Tib lub sijhawm, glucagon zais cia yog suppressed. Nrog lub qog ntshav qab zib, lub zog cia ntawm glucagon zais cia yog tswj. Lixisenatide ua rau kom lub plab khiav tawm hauv lub plab, txo kev nrawm nrawm uas cov piam thaj tau los ntawm cov zaub mov hauv cov ntshav.

Thaum siv ib zaug ib hnub rau cov neeg mob uas muaj ntshav qab zib hom 2, lixisenatide txhim kho glycemic tswj vim muaj kev cuam tshuam sai thiab ntev ntawm kev txo qis qabzib ntau tom qab noj mov thiab hauv plab tas.

Cov nyhuv ntawm cov kua qab zib tom qab tau pom tseeb hauv kev tshawb nrhiav 4 lub lim tiam, hauv kev sib piv nrog liraglutide 1.8 mg ib hnub ib zaug ua ke nrog metformin. Qhov txo qis los ntawm theem pib ntawm PPC qhov ntsuas ntawm 0: 30–4: 30 h ntawm ntshav ntshav qab zib tom qab kuaj cov zaub mov yog:

–12.61 teev * mmol / L (-227.25 teev * mg / dL) hauv cov pab pawg lixisenatide thiab

- 4.04 teev * mmol / L (–72.83 teev * mg / dL) hauv cov pab pawg siab. Qhov no kuj tau lees paub hauv kev tshawb nrhiav 8 lub lim tiam piv rau liraglutide tshuaj ua ntej noj tshais ua ke nrog cov tshuaj insulin glargine nrog lossis tsis muaj metformin.

Cov chaw kuaj mob tau zoo thiab Kev Nyab Xeeb

Hauv kev ua tiav theem III cov kev tshawb fawb, nws tau sau tseg tias thaum kawg ntawm lub sijhawm 24-lub lim tiam ntawm kev kho mob, ntau dua 90% ntawm cov neeg mob tau tuaj yeem tswj kev saib xyuas ntawm Lixumia 20 μg ib hnub ib zaug.

Ntxiv tshuaj ntxiv nrog rau cov tshuaj tiv thaiv kab mob hauv lub qhov ncauj

Qhov kawg ntawm lub sijhawm 24 lub lis piam kev kho mob nrog Lixumia, ua ke nrog metformin, sulfonylurea, pioglitazone, lossis kev sib xyaw ntawm cov tshuaj no, pom tias muaj kev cuam tshuam tseem ceeb hauv kev txo ntshav ntshav HbA1c thiab 2-teev postprandial qab zib tom qab noj mov sib piv nrog cov placebo. Kev txo qis hauv HbA1c yog qhov tseem ceeb thaum cov tshuaj tau txhaj ib hnub ib zaug, tsis hais nws siv thaum sawv ntxov lossis thaum yav tsaus ntuj. Qhov kev kis tus kab mob HbA1c no tau siv sijhawm ntev nyob rau hauv cov kev tshawb fawb mus sij hawm ntev ntev txog li 76 lub lis piam.

Postprandial Qib Qib Qib

Kev kho mob Lixumia ua rau txo qis 2-teev nyob tom qab kev noj qab haus huv tom qab sim noj mov, zoo tshaj rau cov placebo, tsis hais txog kev kho mob yooj yim.

Thaum kawg ntawm lub ntsiab kev kho mob 24 lub lis piam, Lixumia txoj kev kho nyob rau hauv kev sib xyaw nrog metformin thiab / lossis sulfonylurea hauv txhua qhov kev tswj xyuas tau ua rau muaj kev hloov pauv hauv lub cev nyhav li ntawm –1.76 kg txog .92.96 kg.

Kev hloov lub cev qhov hnyav los ntawm thawj theem hauv thaj tsam ntawm - 0.38 kg txog -1.80 kg kuj tau pom nyob rau hauv cov neeg mob tau txais lixisenatide ntxiv nrog rau qhov ntsuas tshwj xeeb ntawm basal insulin, lossis hauv kev sib xyaw nrog metformin lossis sulfonylurea.

Hauv cov neeg mob uas tau pib siv cov tshuaj insulin, hauv cov pab pawg lixisenatide, lub cev qhov hnyav tseem yuav luag tsis hloov, thaum nyob hauv cov placebo pab pawg tau nce ntxiv. Hauv cov kev tshawb fawb mus ntev ntev txog li 76 lub lis piam, qhov hnyav hnyav dua.

Cov kev tshawb fawb soj ntsuam ntawm Lixumia qhia txhim kho beta cell muaj nuj nqi raws li ntsuas los ntawm homeostatic beta cell ua haujlwm kev ntsuas tus qauv (HOMO-β / HOMA-β).

Kev Ntsuas Kab Mob Ntsuas

Hauv txhua qhov kev sim tshuaj placebo hauv theem III, cov neeg mob ntshav qab zib hom 2 tsis qhia kev nce siab hauv nruab nrab lub plawv dhia.

Neeg laus

Cov neeg hnub nyoog ≥70 xyoo

Lixisenatide muab txoj kev txhim kho tseem ceeb hauv glycated hemoglobin (HbA1c) (hloov los ntawm -0.64% piv nrog cov placebo, 95% kev ntseeg siab rau lub sijhawm (CI): los ntawm -0.810% rau -0.464%, p

Phiv phiv ntawm Lixumium daws

Cov Ntsiab Lus Kev Ruaj Ntseg

Ntau tshaj 2,600 tus neeg mob hauv 8 qhov kev tshawb nrhiav tshuaj placebo lossis kev tshawb fawb theem III nrog kev tswj hwm tau txais Lixumia yog kev kho mob monotherapy lossis kev sib xyaw nrog metformin, sulfonylurea (nrog lossis tsis muaj metformin) lossis insulin basal (nrog lossis tsis muaj metformin lossis nrog sulfonylurea) lossis tsis muaj nws).

Feem ntau cov kev phiv tshuaj pom tias tshwm sim thaum kuaj mob yog xeev ntuav, ntuav, thiab zawv plab. Cov kev tawm tsam feem ntau yog ua rau me ntsis thiab dhau los.

Kuj tseem muaj tus mob hypoglycemia (thaum Lixumia tau siv nrog sulfonylurea thiab / lossis insulin basal) thiab mob taub hau. Kev ua xua tau pom nyob rau hauv 0.4% ntawm cov neeg mob siv Lixumia.

Hauv qab no yog cov kev phiv tshuaj uas tshwm sim nrog qhov zaus ntawm> 5%, yog tias qhov kev tshwm sim muaj ntau dua ntawm cov neeg mob tau txais Lixumia dua li ntawm cov neeg mob tau txais tag nrho cov tshuaj sib piv, tseem muaj cov kev tsis haum nrog ntau zaus ntawm ≥ 1% hauv pawg neeg mob uas tau txais Lixumia, yog tias qhov zaus tshwm sim muaj 2 zaug ntau dua li zaus ntawm cov pawg ntawm cov neeg mob tau txais txhua qhov sib piv ntawm cov tshuaj.

Cov kev tsis zoo tshwm sim hauv cov tshuaj placebo thiab theem III kev sim nrog kev tswj hwm tau zoo thaum lub sijhawm kho tag nrho (suav nrog lub sijhawm dhau ntawm lub sijhawm 24-lub lim tiam kho mob hauv kev tshawb fawb nrog ≥ 76 lub lim tiam ntawm kev kho txhua tus).

hypoglycemia (ua ke nrog sulfonylurea thiab / lossis insulin basal)

mob taub hau

xeev siab, ntuav, raws plab

Feem ntau (≥ 1/100 txog 5% rog lub hnub so bolsan zhalymsyz reactionar berylgen, tus neeg yos hav zoov payda boli zhіlіgі barlyқ salistyru tshuaj taryn alғan edelushіler toptara arasynda zhіlіlіndydydelda 1%

Placebo-baқılanatyn belne belsendi baқylanatyn III theem ғ zertteulerde bүkіl emdela kezeңi boyina (bүkіl emdeudің ≥ 76 aptasynda zertteulerde negizy-24

Cov lus qhia tshwj xeeb

- nrog rau qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg thiab metformin,

- nrog monotherapy nrog basal insulin,

- nrog kev sib xyaw ntawm basal insulin thiab metformin.

Nyob rau lub sijhawm kev kho mob tag nrho, thaum Lixumia tau siv nrog kev kho mob monotherapy nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg, hypoglycemia nrog cov kev mob tshwm sim hauv 22.7% ntawm cov neeg mob kho nrog Lixumia thiab hauv 15,2% ntawm cov neeg mob uas tau txais placebo. Thaum Lixumia tau siv nyob rau hauv peb zaug ua ke nrog qhov ncauj tshuaj hypoglycemic ntawm sulfonylurea pawg thiab basal insulin, hypoglycemia nrog cov kev mob tshwm sim hauv 47.2% ntawm cov neeg mob kho nrog lixisenatide, thiab hauv 21.6% ntawm cov neeg mob kho nrog placebo.

Feem ntau, nyob rau tag nrho lub sijhawm dhau los ntawm kev siv tshuaj hauv cov tswj sim theem III, kev tshwm sim ntawm kev mob ntshav qab zib tsawg nrog kev soj ntsuam mob sib piv rau qhov "tsis tshua muaj" kev txiav txim siab.

Vim tias qhov tshuaj tiv thaiv kab mob muaj peev xwm ntawm cov tshuaj uas muaj cov protein lossis peptides, tom qab kev kho mob nrog Lixumia hauv cov neeg mob, kev tsim cov tshuaj tiv thaiv rau lixisenatide yog ua tau. Thaum kawg ntawm lub sijhawm 24-lub lim tiam kho mob, hauv kev soj ntsuam cov tshuaj placebo, 69.4% ntawm cov neeg mob kho nrog lixisenatide muaj cov txiaj ntsig zoo rau kev muaj cov tshuaj tiv thaiv kab mob rau lixisenatide.Txawm li cas los xij, kev hloov pauv ntawm HbA1c Performance index, piv nrog tias ua ntej kev siv lixisenatide, zoo ib yam, tsis hais qhov zoo lossis qhov tshwm sim ntawm kev soj ntsuam rau qhov muaj cov tshuaj tiv thaiv rau lixisenatide. Ntawm cov neeg mob kho nrog lixisenatide nrog HbA1c tus qhab nia, 79.3% muaj qhov ntsuas tsis zoo rau qhov muaj cov tshuaj tiv thaiv kab mob rau lixisenatide lossis titer ntawm cov tshuaj tiv thaiv kom lixisenatide qis dua qhov qis ntawm nws qhov ntau, thiab qhov seem 20.7% ntawm cov neeg mob muaj qhov ntsuas seb muaj ntau npaum li cas kuaj pom cov tshuaj tiv thaiv kom tau lixisenatide.

Muaj tsis muaj tus ntoo khaub lig-immunological reactivity nrog haiv neeg glucagon los yog endogenous GLP-1.

Tsuas tshuaj thiab tswj hwm

Thawj koob tshuaj: noj tshuaj pib nrog 10 mcg Lixumia ib hnub ib zaug rau 14 hnub.

Kev noj tshuaj txij nkawm: kev tswj hwm qhov tshuaj tiv thaiv kab mob ruaj khov ntawm 20 mcg Lixumia ib hnub ib zaug pib hnub 15.

Rau cov tshuaj tu, Lixumia txhaj tshuaj ntawm 20 mcg yog siv. Rau qhov pib txhaj tshuaj, sib tov ntawm 10 Lg Lixumia txhaj tshuaj yog siv.

Liksumiya tau qhia ib hnub ib zaug, ib teev ua ntej ib pluas noj twg. Tshaj li, qhov kev txhaj tshuaj Lixumia yog ua txhua hnub ua ntej noj mov, thaum lub sijhawm yooj yim tshaj plaws ntawm kev tswj hwm tau xaiv. Yog tias ib koob tshuaj Lixumia tsis dhau, yuav tsum tau txhaj tshuaj ib teev ua ntej noj mov tom ntej.

Thaum sau tshuaj Lixumia, ntxiv rau kev tau txais kev kho mob nrog metformin, qhov kev noj tshuaj tam sim no ntawm metformin kuj tseem yuav tsis hloov.

Thaum sau tshuaj Lixumia, ntxiv rau kev tau txais kev kho mob nrog sulfonylurea lossis basal insulin, koob tshuaj sulfonylurea lossis basal insulin yuav raug txo kom txo qis kev pheej hmoo ntawm hypoglycemia.

Lixumia yuav tsum tsis txhob raug sau ua ke nrog basal insulin thiab sulfonylurea vim qhov muaj feem yuav ua rau tus mob ntshav qab zib tsawg (saib "Cov lus qhia tshwj xeeb").

Kev siv Lixumia tsis tas yuav tsum muaj kev saib xyuas tshwj xeeb cov ntshav qabzib. Txawm li cas los xij, thaum siv ua ke nrog sulfonylurea lossis basal insulin, kev saib xyuas ntshav qabzib lossis kev soj ntsuam ntshav qabzib nws tus kheej yuav tsum tau tsim nyog txhawm rau txhawm rau kho cov tshuaj sulfonylurea lossis basal insulin.

Raws li lub hnub nyoog, tsis tas yuav hloov kho qhov tshuaj.

Cov neeg mob uas lub raum tsis ua hauj lwm zoo

Hauv cov neeg mob uas muaj mob mentsis los sis tsis zoo lub raum kev ua haujlwm, tsis tas yuav hloov kho dua. Tsis muaj kev paub txog kev kho mob rau cov neeg mob uas muaj lub raum tsis ua haujlwm zoo (creatinine tshem tawm tsawg dua 30 ml / min) lossis hauv cov neeg mob uas mob raum ntu kawg, thiab vim li no, Lixumia tsis pom zoo rau cov pab pawg ntawm cov neeg mob.

Cov neeg mob uas muaj lub siab ua haujlwm tsis zoo

Rau cov neeg mob ua lub siab tsis ua hauj lwm, tsis tas yuav hloov kho qhov tshuaj. Kev saib xyuas cov menyuam yaus

Cov kev nyab xeeb thiab ua haujlwm ntawm cov lixisenatide hauv cov menyuam yaus thiab cov tub ntxhais hluas hnub nyoog qis dua 18 xyoo tsis tau teeb tsa. Tsis muaj ntaub ntawv muaj.

Tus thawj coj kev tswj hwm

Lycumum yog qhia rau kev coj ua subcutaneous hauv tus ncej puab, plab los yog xub pwg. Tsis txhob txhaj tshuaj rau pob ntseg los yog intramuscularly.

Lixumia yuav tsum tsis txhob siv yog tias nws tau khov. Liksumiya tuaj yeem siv nrog cov rab koob uas siv pov tseg los ntawm 29 txog 32 caliber rau ib xaum xaum xim. Cov koob txhaj koob txhaj tshuaj tsis suav nrog.

Nws yog ib qho tsim nyog yuav tau qhia tus neeg mob kom muab cov koob txhaj tshuaj pov tseg tom qab txhua tus siv raws li cov cai ntawm cov cai hauv zos pov tseg thiab khaws cov xaum xaum xaim tsis muaj rab koob tso. Qhov no pab tiv thaiv kev ua paug thiab txhaws ntawm rab koob. Tus cwj mem tau tsuas yog siv los ntawm ib tus neeg mob nkaus xwb.

Txhua yam tshuaj tsis raug cai lossis cov khoom siv pov tseg yuav tsum muab pov tseg raws li txoj cai pov tseg hauv zos.

Thaum tsis muaj kev kawm tshawb paub txog kev sib raug zoo, cov tshuaj yuav tsum tsis txhob sib xyaw nrog lwm cov tshuaj.

Cov tshuaj sib cuam tshuam

Lixisenatide yog peptide uas tsis yog metabolized nrog kev koom tes ntawm cytochrome P450. Hauv kev tshawb pom nyob hauv vitro, lixisenatide tsis cuam tshuam rau kev ua haujlwm ntawm cov cytochrome P450 isoenzymes lossis tib neeg thauj neeg.

Kev maj mam khiav tawm ntawm lub plab zom mov nrog kev siv lixisenatide tuaj yeem txo tus nqi nqus ntawm cov tshuaj noj ntawm qhov ncauj. Nws yog qhov yuav tsum tau ua tib zoo saib xyuas cov neeg mob uas tau txais cov tshuaj nrog qhov nqaim kev ntsuas qis lossis cov tshuaj uas yuav tsum tau ua tib zoo tshuaj xyuas, tshwj xeeb tshaj yog thaum pib kho nrog lixisenatide Txog lixisenatide, cov tshuaj no yuav tsum noj nyob rau hauv ib txwm muaj. Yog tias cov tshuaj zoo li no yuav tsum tau noj nrog zaub mov, cov neeg mob yuav tsum raug qhia kom coj lawv nrog zaub mov thaum ua tau thaum lixisenatide tsis siv.

Rau cov tshuaj noj qhov ncauj, xws li tshuaj tua kab mob, uas, tshwj xeeb tshaj yog hais txog qhov ua tau zoo, nyob ntawm qhov ua kom lub siab xav, cov neeg mob yuav tsum raug qhia kom tsawg kawg 1 teev ua ntej lossis 4 teev tom qab txhaj tshuaj lixisenatide.

Enteric-soluble dosage cov ntaub ntawv muaj tshuaj rhiab rau kev zom zaub mov hauv plab yuav tsum siv 1 teev ua ntej lossis 4 teev tom qab txhaj tshuaj lixisenatide.

Paracetamol tau siv los ua qauv tshuaj txhawm rau txhawm rau tshuaj xyuas qhov txiaj ntsig ntawm lixisenatide ntawm kev khiav tawm ntawm lub plab zom mov. Tom qab thov kev noj tshuaj ib zaug xwb ntawm paracetamol 1000 mg, thaj chaw hauv qab nkhaus (PPC) thiab t1 / 2 ntawm paracetamol tseem tsis hloov, tsis hais lub sijhawm ntawm kev siv (ua ntej lossis tom qab txhaj tshuaj lixisenatide). Thaum nws siv 1 teev lossis 4 teev tom qab 10 μg ntawm lixisenatide, Cmax ntawm paracetamol poob, feem, los ntawm 29% thiab 31%, thiab qhov nruab nrab tmax tau qeeb qeeb, ntsig txog, los ntawm 2.0 thiab 1.75 teev. Nrog rau kev siv 20 μg ntawm kev saib xyuas cov koob tshuaj, ib qho qeeb ntxiv ntawm tmax thiab txo qis Cmax ntawm paracetamol tau kwv yees.

Tsis muaj kev cuam tshuam dab tsi rau Cmax thiab tmax ntawm paracetamol thaum siv cov tshuaj paracetamol siv 1 teev ua ntej kev siv lixisenatide.

Raws li cov ntaub ntawv saum toj no, tsis tas yuav tsum muaj kev hloov kho tshuaj paracetamol, tab sis Tmax qhov txuas ntxiv tau pom thaum paracetamol npaj siab 1-4 teev tom qab noj lixisenatide yuav tsum xav txog thaum pib sai ntawm kev nqis tes xav tau.

Tom qab thov kev noj tshuaj ib zaug xwb ntawm qhov ncauj noj kom tsis txhob muaj menyuam yaus (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) 1 teev ua ntej lossis 11 teev tom qab thov 10 μg lixisenatide, Smax, PPC, t1 / 2 thiab tmax ntawm ethinyl estradiol thiab levonorgestrel tseem tsis hloov.

Kev siv qhov ncauj tshuaj tiv thaiv 1 teev lossis 4 teev tom qab siv lixisenatide tsis cuam tshuam rau AUC thiab t1 / 2 ntawm ethinyl estradiol thiab levonorgestrel, thaum Cmax ntawm ethinyl estradiol poob qis, feem, los ntawm 52% thiab 39%, thiab Cmax ntawm levonorgestrel txo qis los ntawm 46%, thiab 20%, thiab tus nqi nruab nrab ntawm tmax maj mam los ntawm 1-3 teev.

Qhov kev txo qis ntawm Cmax muaj qhov tsawg tsawg rau kev kho mob, thiab kev kho qhov ncauj ntawm kev tiv thaiv kab mob hauv qhov ncauj tsis tas yuav tsum tau ua.

Thaum siv 20 μg lixisenatide sib xyaw nrog 40 mg ntawm atorvastatin thaum sawv ntxov rau 6 hnub, cov nyhuv ntawm atorvastatin tsis hloov, thaum Cmax txo los ntawm 31% thiab tmax nce los ntawm 3.25 teev.

Xws li nce rau tmax tsis pom yog tias atorvastatin tau siv thaum yav tsaus ntuj, thiab lixisenatide thaum sawv ntxov, tab sis PPK thiab Cmax ntawm atorvastatin, ntsig txog, nce 27% thiab 66%.

Cov kev hloov pauv no tsis yog qhov tseem ceeb hauv lub chaw kho mob, yog li cov tshuaj hloov kho atorvastatin tsis tas yuav tsum tau ua thaum nws siv nrog lixisenatide.

Warfarin thiab lwm yam tshuaj txuas rau kev txij nkawm

Tom qab cov tshuaj confitant siv 25 mg ntawm warfarin nrog ntau dua lixisenatide 20 μg, tsis muaj kev cuam tshuam rau AUC lossis INR (thoob ntiaj teb li qub), thaum lub Cmax index tau txo los ntawm 19% thiab tmax tus nqi nce txog 7 teev.

Raws li cov txiaj ntsig no, kev hloov tshuaj ntawm warfarin tsis tas yuav tsum tau ua thaum nws siv nrog kev sib xyaw nrog lixisenatide, txawm li cas los xij, kev saib xyuas ntau zaus ntawm INR hauv cov neeg mob noj warfarin thiab / lossis coumarin derivatives yog pom zoo thaum pib lossis xaus kev kho mob lixisenatide.

Tom qab ua ke ntawm kev siv lixisenatide 20 μg thiab 0.25 mg ntawm digoxin hauv lub xeev qhov sib luag, PPC ntawm digoxin tsis hloov pauv. Tus nqi ntawm tmax ntawm digoxin tau nce los ntawm 1.5 teev, thiab tus nqi ntawm Cmax nqis los ntawm 26%.

Raws li cov txiaj ntsig no, kev sib zog hloov kho cov digoxin tsis tas yuav tsum tau ua thaum nws siv nrog kex lienatide.

Tom qab cov tshuaj sib xyaw nrog lixisenatide 20 μg thiab 5 mg ntawm ramipril rau 6 hnub, PPK ramipril nce 21%, thaum lub Cmax poob qis los ntawm 63%. Qhov taw qhia ntawm PPC thiab Cmax ntawm lub zog metabolite (ramiprilat) tsis hloov pauv. Lub tmax ntawm ramipril thiab ramiprilat ntau zog los ntawm kwv yees li 2.5 teev.

Raws li cov txiaj ntsig no, kev txhaj tshuaj ntawm ramipril tsis tas yuav tsum muaj thaum nws siv nrog kexisenatide.

Noj ntau dhau

Thaum lub sijhawm sim tshuaj, cov tshuaj lixisenatide txog 30 mcg tau siv ob zaug ib hnub rau cov neeg mob ntshav qab zib hom 2 hauv kev kawm 13 lub lis piam. Muaj neeg coob leej ntau tus mob lub plab zom zaws.

Yog tias muaj kev noj ntau dhau, ua raws li kev kho mob cov tsos mob thiab cov tsos mob, tus neeg mob yuav tsum pib kev pab txhawb nqa tsim nyog, thiab cov koob tshuaj lixisenatide yuav tsum tau txo kom tsawg dua cov koob tshuaj.