Pharmacokinetics/Pharmacodynamics of Albiglutide

Condition(s) targeted: Diabetes Mellitus, Type 2

Intervention: albiglutide (GSK716155) (Biological); albiglutide (GSK716155) (Biological)

Phase: Phase 2

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

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.

Official title: A Multidose Study in Subjects With Type 2 Diabetes Mellitus to Assess the Pharmacokinetics and Pharmacodynamics of Albiglutide

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase

Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase

Secondary outcome:

Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP)

Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase

AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase

Tmax and Tlag of Albiglutide in the BE Phase

Cmax of Albiglutide in the BE Phase

t1/2 of Albiglutide in the BE Phase

Apparent Clearance of Albiglutide in the BE Phase

Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Number of Participants With Indicated Adverse Events of Special Interest

Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit

Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit

Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17

Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit

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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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

GSK Investigational Site, Dothan, Alabama 36301, United States

GSK Investigational Site, Long Beach, California 90806, United States

GSK Investigational Site, Riverside, California 92506, United States

GSK Investigational Site, Hallandale Beach, Florida 33009, United States

GSK Investigational Site, Jacksonville, Florida 32205, United States

GSK Investigational Site, Orlando, Florida 32822, United States

GSK Investigational Site, Tampa, Florida 33603, United States

GSK Investigational Site, Blue Ridge, Georgia 30513, United States

GSK Investigational Site, Lexington, Kentucky 40504, United States

GSK Investigational Site, Paducah, Kentucky 42003, United States

GSK Investigational Site, Gulfport, Mississippi 39501, United States

GSK Investigational Site, Picayune, Mississippi 39466, United States

GSK Investigational Site, Omaha, Nebraska 68131, United States

GSK Investigational Site, Greensboro, North Carolina 27405, United States

GSK Investigational Site, Columbus, Ohio 43213, United States

GSK Investigational Site, Mason, Ohio 45040, United States

GSK Investigational Site, Bensalem, Pennsylvania 19020, United States

GSK Investigational Site, Columbia, South Carolina 29201, United States

GSK Investigational Site, North Myrtle Beach, South Carolina 29582, United States

GSK Investigational Site, Simpsonville, South Carolina 29681, United States

GSK Investigational Site, Clarksville, Tennessee 37043, United States

GSK Investigational Site, McKenzie, Tennessee 38201, United States

GSK Investigational Site, Houston, Texas 77074, United States

GSK Investigational Site, Irving, Texas 75039, United States

GSK Investigational Site, San Antonio, Texas 78215, United States

GSK Investigational Site, San Antonio, Texas 78218, United States

GSK Investigational Site, San Antonio, Texas 78229, United States

GSK Investigational Site, Sugarland, Texas 77479, United States

GSK Investigational Site, Bountiful, Utah 84010, United States

GSK Investigational Site, Lewisburg, West Virginia 24901, United States

Starting date: July 2011
Last updated: May 29, 2014