Pharmacokinetics/Pharmacodynamics of Albiglutide

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

Time frame · Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

To assess the bioequivalence of the two formulations of albiglutide, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter AUC(0-inf) estimated from the BE Phase. AUC is a measure of how much albiglutide is in the blood at certain time points. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

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

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

To assess the bioequivalence of the two formulations of study drug, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter Cmax estimated from the BE phase. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

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

Time frame · Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up)

The trough concentration of albiglutide at Week 5, Week 9, Week 13, Week 17 (EOT), and Week 25 (Follow-up) following multiple-dose administration was estimated. The time and date of sample collection pre-dose was to be recorded.

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

Time frame · Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up)

The presence of anti-albiglutide antibodies after repeat-dose administration was assessed using a qualified enzyme-linked immunosorbent assay. The assay involved screening, confirmation, and titration steps (tiered-testing approach). The number of participants who tested positive for anti-albiglutide antibodies are presented by visit.

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

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

The area under the concentration-time (AUC) curve from time zero to the last quantifiable concentration (0-last) and AUC (0-inf) of albiglutide in the BE Phase were measured. AUC is a measure of how much albiglutide is in the blood at certain time points. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

Tmax and Tlag of Albiglutide in the BE Phase

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

Time of the maximum observed plasma concentration (tmax) and the observed time prior to the first quantifiable plasma concentration (tlag) of albiglutide in the BE Phase were measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

Cmax of Albiglutide in the BE Phase

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

Cmax of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

t1/2 of Albiglutide in the BE Phase

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

The terminal elimination half-life (t1/2) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

Apparent Clearance of Albiglutide in the BE Phase

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

The apparent clearance (CL/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

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

Time frame · Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose

The apparent volume of distribution in the terminal phase (V/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.

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

Time frame · Baseline and Week 17

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. This analysis used the last observation carried forward (LOCF) method for missing post-Baseline HbA1c values. HbA1c values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on analysis of covariance (ANCOVA): Change = treatment + Baseline HbA1c + age category + weight category + background antidiabetic therapy category.

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

Time frame · Baseline and Week 17

This analysis used the LOCF method for missing post-Baseline FPG values. FPG values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on ANCOVA: Change = treatment + Baseline FPG + age category + weight category + background antidiabetic therapy category.