Clinical trial NCT01357889: Pharmacokinetics/Pharmacodynamics of Albiglutide
Official title: A Multidose Study in Subjects With Type 2 Diabetes Mellitus to Assess the Pharmacokinetics and Pharmacodynamics of Albiglutide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: pharmacokinetics
pharmacodynamics
GSK716155
albiglutide
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-05-23
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The first part of the study includes a single dose treatment period to evaluate the pharmacokinetic bioequivalence of a subcutaneous injection of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic and pharmacodynamic parameters and safety and tolerability of repeat doses of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.

Detailed description: This is a randomized, double-blind, multicenter, 2 parallel group study. The first part of the treatment period will evaluate the pharmacokinetic bioequivalence of a single dose of a subcutaneous injection of 30mg of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic parameters, pharmacodynamic parameters, immunogenicity, effects on glycosylated hemoglobin and fasting plasma glucose, and safety and tolerability of repeat doses of subcutaneous injections of 30mg of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.

Eligibility criteria: Inclusion Criteria:

* Subjects with a historical diagnosis of type 2 diabetes mellitus who are experiencing inadequate glycemic control on their current regimen of diet and exercise or on a stable dose of metformin
* Body mass index ≥20 kg/m2 and ≤45 kg/m2
* Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
* Thyroid-stimulating hormone level is normal or clinically euthyroid
* Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception.

Exclusion Criteria:

* Current ongoing symptomatic biliary disease or history of pancreatitis
* History of significant GI surgery
* Recent clinically significant cardiovascular and/or cerebrovascular disease
* History of human immunodeficiency virus infection
* History of, or current hepatic disease
* History of alcohol or substance abuse
* Female subject is pregnant, lactating, or \<6 weeks postpartum
* History of type 1 diabetes
* Receipt of any investigational drug within the 30 days, or 5 half-lives whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of any GLP-1 agents including albiglutide
* History of, or family history of thyroid disease

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase
timeFrame: Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Secondary outcomes:
measure: Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP)
timeFrame: Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up)
measure: Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase
timeFrame: Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up)
measure: AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Tmax and Tlag of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Cmax of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: t1/2 of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Apparent Clearance of Albiglutide in the BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase
timeFrame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17
timeFrame: Baseline and Week 17
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17
timeFrame: Baseline and Week 17
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
timeFrame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinued active participation in the study
measure: Number of Participants With Indicated Adverse Events of Special Interest
timeFrame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinue active participation in the study
measure: Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit
timeFrame: Week 1 through Week 25
measure: Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit
timeFrame: Week 1 through Week 25
measure: Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17
timeFrame: Screening and Week 17
measure: Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit
timeFrame: Week 1 through Week 25
Other outcomes:
Locations:
city: Dothan
country: United States
facility: GSK Investigational Site
state: Alabama
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: Hallandale Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Blue Ridge
country: United States
facility: GSK Investigational Site
state: Georgia
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Paducah
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Gulfport
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Picayune
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Mason
country: United States
facility: GSK Investigational Site
state: Ohio
city: Bensalem
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: North Myrtle Beach
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Clarksville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: McKenzie
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Irving
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Sugarland
country: United States
facility: GSK Investigational Site
state: Texas
city: Bountiful
country: United States
facility: GSK Investigational Site
state: Utah
city: Lewisburg
country: United States
facility: GSK Investigational Site
state: West Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Young MA, Wald JA, Matthews JE, Scott R, Hodge RJ, Zhi H, Reinhardt RR. Clinical pharmacology of albiglutide, a GLP-1 receptor agonist. Postgrad Med. 2014 Nov;126(7):84-97. doi: 10.3810/pgm.2014.11.2836.