PMID- 19187286
OWN - NLM
STAT- MEDLINE
DCOM- 20100511
LR  - 20231120
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 11
IP  - 5
DP  - 2009 May
TI  - Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a 
      long-acting glucagon-like peptide-1 mimetic, in healthy subjects.
PG  - 498-505
LID - 10.1111/j.1463-1326.2008.00992.x [doi]
AB  - AIMS: Albiglutide is a glucagon-like peptide-1 (GLP-1) mimetic generated by 
      genetic fusion of a dipeptidyl peptidase-IV-resistant GLP-1 dimer to human 
      albumin. Albiglutide was designed to retain the therapeutic effects of native 
      GLP-1 while extending its duration of action. This study was conducted to 
      determine the pharmacokinetics and initial safety/tolerability profile of 
      albiglutide in non-diabetic volunteers. METHODS: In this single-blind, 
      randomized, placebo-controlled trial, 39 subjects (18-60 years, body mass index 
      19.9-35.0 kg/m(2)) received placebo (n = 10) or escalating doses of albiglutide 
      (n = 29) on days 1 and 8 in the following sequential cohorts: cohort 1: 0.25 + 1 
      mg; cohort 2: 3 + 6 mg; cohort 3: 16 + 24 mg; cohort 4: 48 + 60 mg; and cohort 5: 
      80 + 104 mg. Dose proportionality was evaluated based on area under the plasma 
      drug concentration versus time curve [area under the curve (AUC((0-7 days)))] and 
      maximum plasma drug concentration (C(max)) for cohorts 2-5 during week 1. 
      RESULTS: Albiglutide had a terminal elimination half-life (T(1/2)) of 6-8 days 
      and time to maximum observed plasma drug concentration (T(max)) of 3-4 days. A 
      greater-than-dose proportional increase in albiglutide exposure was observed. 
      Albiglutide demonstrated a dose-dependent trend in reductions of glucose weighted 
      mean AUC and fructosamine levels in healthy subjects. The incidence and severity 
      of adverse events (AEs) was similar between placebo and albiglutide groups. 
      Headache was the most frequent drug-related AE, followed by constipation, 
      flatulence and nausea. CONCLUSIONS: Albiglutide has a half-life that favours once 
      weekly or less frequent dosing with an acceptable safety/tolerability profile in 
      non-diabetic subjects.
FAU - Bush, M A
AU  - Bush MA
AD  - GlaxoSmithKline, Research Triangle Park, NC, USA.
FAU - Matthews, J E
AU  - Matthews JE
FAU - De Boever, E H
AU  - De Boever EH
FAU - Dobbins, R L
AU  - Dobbins RL
FAU - Hodge, R J
AU  - Hodge RJ
FAU - Walker, S E
AU  - Walker SE
FAU - Holland, M C
AU  - Holland MC
FAU - Gutierrez, M
AU  - Gutierrez M
FAU - Stewart, M W
AU  - Stewart MW
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080211
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 5E7U48495E (rGLP-1 protein)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Blood Glucose/drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glucagon-Like Peptide 1/analogs & derivatives/*pharmacology
MH  - Glycated Hemoglobin/metabolism
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2009/02/04 09:00
MHDA- 2010/05/12 06:00
CRDT- 2009/02/04 09:00
PHST- 2009/02/04 09:00 [entrez]
PHST- 2009/02/04 09:00 [pubmed]
PHST- 2010/05/12 06:00 [medline]
AID - DOM992 [pii]
AID - 10.1111/j.1463-1326.2008.00992.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2009 May;11(5):498-505. doi: 
      10.1111/j.1463-1326.2008.00992.x. Epub 2008 Feb 11.