Trial Outcomes & Findings for Safety and Efficacy Study of Albiglutide in Type 2 Diabetes (NCT NCT00849017)

Last Updated: 2017-01-09

Results Overview

Glycated hemoglobin (HbA1c) is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 52 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (\<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate. The last observation carried forward (LOCF) method was used to impute missing post-BL HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

309 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2017-01-09

Participant Flow

Participants (par.) who met eligibility criteria and completed a 4 week Run-in/Stabilization Period were then randomized to a 156-week Treatment Period, followed by 8 weeks of post-treatment follow-up. A total of 479 par. were screened; 309 par. were randomized, and 301 par. received \>=1 treatment dose.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Treatment Period (156 Weeks) STARTED	101	101	99
Treatment Period (156 Weeks) COMPLETED	58	68	57
Treatment Period (156 Weeks) NOT COMPLETED	43	33	42
Follow-up Period (8 Weeks) STARTED	101	101	99
Follow-up Period (8 Weeks) COMPLETED	76	83	74
Follow-up Period (8 Weeks) NOT COMPLETED	25	18	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Treatment Period (156 Weeks) Adverse Event	5	6	15
Treatment Period (156 Weeks) Noncompliance	3	3	4
Treatment Period (156 Weeks) Lost to Follow-up	10	7	8
Treatment Period (156 Weeks) Withdrawal by Subject	18	14	11
Treatment Period (156 Weeks) Physician Decision	0	2	1
Treatment Period (156 Weeks) Termination of Study/ Site by GSK	3	1	1
Treatment Period (156 Weeks) Increased Calcitonin	1	0	0
Treatment Period (156 Weeks) Physician Discontinued-Thrombocytopenia	1	0	0
Treatment Period (156 Weeks) Participant Moved to Africa	1	0	0
Treatment Period (156 Weeks) Pregnancy	1	0	1
Treatment Period (156 Weeks) Participant Decided to Move Out of State	0	0	1
Follow-up Period (8 Weeks) Adverse Event	1	0	0
Follow-up Period (8 Weeks) Noncompliance	2	1	0
Follow-up Period (8 Weeks) Lost to Follow-up	13	12	16
Follow-up Period (8 Weeks) Did Not Enter Follow-up Period	1	1	4
Follow-up Period (8 Weeks) Withdrawal by Subject	4	2	3
Follow-up Period (8 Weeks) Physician Decision	0	1	1
Follow-up Period (8 Weeks) Termination of Study/ Site by GSK	3	1	1
Follow-up Period (8 Weeks) Participant Relocating to Africa	1	0	0

Baseline Characteristics

Safety and Efficacy Study of Albiglutide in Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=101 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=101 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=99 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Total n=301 Participants Total of all reporting groups
Age, Continuous	53.1 Years STANDARD_DEVIATION 11.68 • n=93 Participants	53.6 Years STANDARD_DEVIATION 10.89 • n=4 Participants	52.0 Years STANDARD_DEVIATION 11.75 • n=27 Participants	52.9 Years STANDARD_DEVIATION 11.43 • n=483 Participants
Gender Female	43 Participants n=93 Participants	43 Participants n=4 Participants	49 Participants n=27 Participants	135 Participants n=483 Participants
Gender Male	58 Participants n=93 Participants	58 Participants n=4 Participants	50 Participants n=27 Participants	166 Participants n=483 Participants
Race/Ethnicity, Customized African American/African Heritage	14 Participants n=93 Participants	10 Participants n=4 Participants	14 Participants n=27 Participants	38 Participants n=483 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	3 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	5 Participants n=483 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	2 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	6 Participants n=483 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	5 Participants n=483 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	77 Participants n=93 Participants	85 Participants n=4 Participants	78 Participants n=27 Participants	240 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: Intent-to-Treat (ITT) Population with LOCF: all randomized par. who received \>=1 dose of study medication and who had a BL assessment and \>=1 post-BL assessment of HbA1c. Only par. with a value at BL and at the specified visit were analyzed. Values were carried forward for par. who were rescued or discontinued from active treatment before Week 52.

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52	0.15 Percentage of HbA1c in the blood Standard Error 0.097	-0.70 Percentage of HbA1c in the blood Standard Error 0.096	-0.89 Percentage of HbA1c in the blood Standard Error 0.097

SECONDARY outcome

Timeframe: Baseline and Weeks 104 and 156

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in HbA1c at Weeks 104 and 156 Week 104, n=21, 39, 42	-0.40 Percentage of HbA1c in the blood Standard Deviation 0.676	-0.93 Percentage of HbA1c in the blood Standard Deviation 1.027	-1.18 Percentage of HbA1c in the blood Standard Deviation 0.909
Change From Baseline in HbA1c at Weeks 104 and 156 Week 156, n=14, 30, 32	-0.61 Percentage of HbA1c in the blood Standard Deviation 0.644	-0.96 Percentage of HbA1c in the blood Standard Deviation 0.968	-1.07 Percentage of HbA1c in the blood Standard Deviation 0.887

SECONDARY outcome

Timeframe: From the start of study medication until the end of the treatment (up to Week 156)

Population: IIT Population. Only those participants with a value at Baseline and at the specified visit were analyzed.

Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: FPG \>=280 milligrams/deciliter (mg/dL) between \>=Week 2 and \<Week 4; FPG \>=250 mg/dL between \>=Week 4 and \<Week 12; HbA1c \>=8.5% and a \<=0.5% reduction from Baseline between \>=Week 12 and \<Week 24; HbA1c \>=8.5% between \>=Week 24 and \<Week 48; HbA1c \>=8.0% between \>= Week 48 and \<Week 156. Participants could have been rescued at any time on or after Week 2. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus 1 day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus 1 day for participants not requiring rescue. This time was divided by 7 to express the result in weeks.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Time to Hyperglycemia Rescue	49.71 Weeks Interval 32.14 to 67.29	118.43 Weeks Interval 79.43 to The 95% CI upper bound is not a available because it is beyond study duration.	NA Weeks There were too few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Intent-to-Treat (ITT) Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.

The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	1.00 Millimoles per liter (mmol/L) Standard Error 0.239	-0.88 Millimoles per liter (mmol/L) Standard Error 0.237	-1.38 Millimoles per liter (mmol/L) Standard Error 0.241

SECONDARY outcome

Timeframe: Baseline and Week 156

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline FPG minus the Baseline FPG.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=29 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=32 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156	-0.23 Millimoles per liter (mmol/L) Standard Deviation 0.794	-1.31 Millimoles per liter (mmol/L) Standard Deviation 1.761	-1.83 Millimoles per liter (mmol/L) Standard Deviation 2.012

SECONDARY outcome

Timeframe: Week 52

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.

The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 52) were assessed.

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 Week 52, HbA1c <6.5%	10 Participants	25 Participants	24 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 Week 52, HbA1c <7.0%	21 Participants	49 Participants	39 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 Week 52, HbA1c <7.5%	34 Participants	59 Participants	62 Participants

SECONDARY outcome

Timeframe: Week 156

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed. This analysis used observed HbA1c values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 156) were assessed.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=30 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=32 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 Week 156, HbA1c <7.0%	8 Participants	18 Participants	19 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 Week 156, HbA1c <7.5%	13 Participants	24 Participants	29 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 Week 156, HbA1c <6.5%	6 Participants	10 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy.

Outcome measures

Outcome measures
Measure	Placebo n=99 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=100 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=97 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Body Weight at Week 52	-0.66 Kilograms Standard Error 0.428	-0.39 Kilograms Standard Error 0.424	-0.86 Kilograms Standard Error 0.432

SECONDARY outcome

Timeframe: Baseline and Week 156

Population: ITT Population with observed values. Only those participants who were available at the indicated time points were analyzed. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=30 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=31 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Body Weight at Week 156	-2.91 Kilograms Standard Deviation 5.213	-1.32 Kilograms Standard Deviation 5.123	-2.24 Kilograms Standard Deviation 5.589

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: MM Population: all participants who participated in the MM tolerance test substudy and who had valid Baseline assessments and Week 52 assessments for at least 1 of the MM lab parameter of C-peptide.

Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was 4 hour c-peptide AUC. The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=16 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=20 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Postprandial Blood Glucose Profile Parameter-4 Hour C-peptide AUC	0.05 Nanomoles/Liter (nmol/L) Standard Error 0.165	0.03 Nanomoles/Liter (nmol/L) Standard Error 0.122	0.08 Nanomoles/Liter (nmol/L) Standard Error 0.108

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: MM Population: all participants who participated in the MM tolerance test substudy and who had valid baseline assessments and Week 52 assessments for at least 1 of the MM lab parameter of glucose. The MM tolerance test was performed only in those participants who additionally consented to participate in.

Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was: 4 hour blood glucose area under urve AUC The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=18 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=19 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Postprandial Blood Glucose Profile Parameter- 4 Hour Blood Glucose AUC	-0.51 Nanomoles/Liter (nmol/L) Standard Error 0.630	-1.74 Nanomoles/Liter (nmol/L) Standard Error 0.414	-2.05 Nanomoles/Liter (nmol/L) Standard Error 0.407

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: MM Population: all participant who participated in the MM tolerance test substudy and who had valid baseline assessments and Week 52 assessments for at least 1 of the MM lab parameters of insulin, proinsulin. The MM tolerance test was performed only in those participants who additionally consented to participate in.

Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameters analyzed were: 4-hour insulin AUC (4 hr Ins AUC), and 4-hour proinsulin AUC (4 hr pro-Ins AUC). The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=16 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg n=20 Participants Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Postprandial Blood Glucose Profile Parameters-4 Hour Insulin AUC and 4 Hour Proinsulin AUC 4hr Ins AUC	49.2 picomoles/Liter (pmol/L) Standard Error 50.12	2.9 picomoles/Liter (pmol/L) Standard Error 36.44	39.9 picomoles/Liter (pmol/L) Standard Error 32.62
Change From Baseline in Postprandial Blood Glucose Profile Parameters-4 Hour Insulin AUC and 4 Hour Proinsulin AUC 4hr Pro-Ins AUC	1.0 picomoles/Liter (pmol/L) Standard Error 17.57	1.9 picomoles/Liter (pmol/L) Standard Error 13.25	-10.7 picomoles/Liter (pmol/L) Standard Error 11.62

SECONDARY outcome

Timeframe: Weeks 8 and 24

Population: ITT population. Only those participants with a PK sample available for analysis at the indicated time points were analyzed.

Albiglutide plasma concentration data was analyzed at Week 8 pre-dose, Week 8 post dose, Week 24 pre-dose and Week 24 post-dose. All participants who received albiglutide were initiated on a 30mg weekly dosing regimen; however, beginning at Week 12, participants in the albiglutide 50 mg treatment group were uptitrated to receive albiglutide 50 mg for the remainder of the study.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Participants received matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 30 mg n=85 Participants Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.	Albiglutide 50 mg Participants received albiglutide 30 mg from Baseline to Week 12 with a forced blinded uptitration to 50 mg at Week 12 as a subcutaneous injection weekly via a fully disposable pen injector system. Participants did not receive investigational product during the Follow-up Period.
Albiglutide Plasma Concentration at Weeks 8 and 24 Week 8 Pre-dose, n=85, 85	1582 nanograms/milliliter (ng/mL) Standard Deviation 735	1433 nanograms/milliliter (ng/mL) Standard Deviation 736	—
Albiglutide Plasma Concentration at Weeks 8 and 24 Week 8 Post-dose, n=87, 80	1900 nanograms/milliliter (ng/mL) Standard Deviation 1093	1759 nanograms/milliliter (ng/mL) Standard Deviation 861	—
Albiglutide Plasma Concentration at Weeks 8 and 24 Week 24 Pre-dose, n=79, 74	1912 nanograms/milliliter (ng/mL) Standard Deviation 966	3060 nanograms/milliliter (ng/mL) Standard Deviation 1610	—
Albiglutide Plasma Concentration at Weeks 8 and 24 Week 24 Post-dose, n=81, 72	2289 nanograms/milliliter (ng/mL) Standard Deviation 1255	3484 nanograms/milliliter (ng/mL) Standard Deviation 2301	—

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 78 other events

Deaths: 0 deaths

Albiglutide 30 mg

Serious events: 15 serious events

Other events: 84 other events

Deaths: 0 deaths

Albiglutide 50 mg

Serious events: 14 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER