Trial Outcomes & Findings for Dose Ranging Study of Albiglutide in Japanese Subjects (NCT NCT01098461)

Last Updated: 2017-01-13

Results Overview

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 Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. Based on Analysis of Covariance (ANCOVA): Change = treatment + Baseline HbA1c + prior therapy. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

215 participants

Primary outcome timeframe

Baseline and Week 16

Results posted on

2017-01-13

Participant Flow

Participants (par.) who met eligibility criteria and completed a 4- to 8-week Run-in Period were then randomized to a 16-week Treatment Period, followed by an 8-week Follow-up Period. A total of 215 participants were randomized, and 212 received \>=1 treatment dose.

Participant milestones

Participant milestones
Measure	Placebo Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Treatment Period (TP) (16 Weeks) STARTED	53	52	54	53
Treatment Period (TP) (16 Weeks) COMPLETED	41	45	53	50
Treatment Period (TP) (16 Weeks) NOT COMPLETED	12	7	1	3
Follow-up (FU) Period (8 Weeks) STARTED	52	52	53	52
Follow-up (FU) Period (8 Weeks) COMPLETED	52	49	52	52
Follow-up (FU) Period (8 Weeks) NOT COMPLETED	0	3	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Treatment Period (TP) (16 Weeks) Persistent Hypoglycemia	10	2	0	0
Treatment Period (TP) (16 Weeks) Adverse Event	1	2	1	3
Treatment Period (TP) (16 Weeks) Withdrawal by Subject	1	2	0	0
Treatment Period (TP) (16 Weeks) Transferred to Oita (Japan)	0	1	0	0
Follow-up (FU) Period (8 Weeks) Withdrawal by Subject	0	1	0	0
Follow-up (FU) Period (8 Weeks) Transferred to Oita (Japan)	0	1	0	0
Follow-up (FU) Period (8 Weeks) Follow-up Not Conducted Due to Earthquak	0	1	1	0

Baseline Characteristics

Dose Ranging Study of Albiglutide in Japanese Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=53 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Total n=212 Participants Total of all reporting groups
Age, Continuous	57.5 Years STANDARD_DEVIATION 11.06 • n=5 Participants	53.3 Years STANDARD_DEVIATION 10.29 • n=7 Participants	58.0 Years STANDARD_DEVIATION 9.30 • n=5 Participants	59.1 Years STANDARD_DEVIATION 8.49 • n=4 Participants	57.0 Years STANDARD_DEVIATION 10.00 • n=21 Participants
Gender Female	16 Participants n=5 Participants	20 Participants n=7 Participants	16 Participants n=5 Participants	12 Participants n=4 Participants	64 Participants n=21 Participants
Gender Male	37 Participants n=5 Participants	32 Participants n=7 Participants	38 Participants n=5 Participants	41 Participants n=4 Participants	148 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	53 participants n=5 Participants	52 participants n=7 Participants	54 participants n=5 Participants	53 participants n=4 Participants	212 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Intent-to-Treat (ITT) Population: all randomized participants with at least one post-Baseline assessment of the primary endpoint, HbA1c. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16	0.28 Percentage of HbA1c in the blood Standard Error 0.099	-0.61 Percentage of HbA1c in the blood Standard Error 0.097	-1.27 Percentage of HbA1c in the blood Standard Error 0.095	-0.82 Percentage of HbA1c in the blood Standard Error 0.096

SECONDARY outcome

Timeframe: Baseline; Week 4, Week 8, Week 12, and Week 16

Population: ITT Population with LOCF. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.

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 Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 Week 4	0.03 Percentage of HbA1c in the blood Standard Deviation 0.349	-0.33 Percentage of HbA1c in the blood Standard Deviation 0.301	-0.61 Percentage of HbA1c in the blood Standard Deviation 0.377	-0.36 Percentage of HbA1c in the blood Standard Deviation 0.383
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 Week 8	0.20 Percentage of HbA1c in the blood Standard Deviation 0.628	-0.59 Percentage of HbA1c in the blood Standard Deviation 0.430	-1.07 Percentage of HbA1c in the blood Standard Deviation 0.578	-0.74 Percentage of HbA1c in the blood Standard Deviation 0.618
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 Week 12	0.24 Percentage of HbA1c in the blood Standard Deviation 0.730	-0.71 Percentage of HbA1c in the blood Standard Deviation 0.464	-1.26 Percentage of HbA1c in the blood Standard Deviation 0.649	-0.84 Percentage of HbA1c in the blood Standard Deviation 0.720
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 Week 16	0.27 Percentage of HbA1c in the blood Standard Deviation 0.743	-0.63 Percentage of HbA1c in the blood Standard Deviation 0.548	-1.29 Percentage of HbA1c in the blood Standard Deviation 0.736	-0.84 Percentage of HbA1c in the blood Standard Deviation 0.875

SECONDARY outcome

Timeframe: Baseline; Week 4, Week 8, Week 12, and Week 16

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. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=51 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 Week 4	0.30 Millimoles per liter (mmol/L) Standard Deviation 1.190	-1.54 Millimoles per liter (mmol/L) Standard Deviation 1.378	-2.27 Millimoles per liter (mmol/L) Standard Deviation 1.465	-1.32 Millimoles per liter (mmol/L) Standard Deviation 1.271
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 Week 8	0.41 Millimoles per liter (mmol/L) Standard Deviation 1.451	-1.54 Millimoles per liter (mmol/L) Standard Deviation 1.585	-2.27 Millimoles per liter (mmol/L) Standard Deviation 1.652	-1.19 Millimoles per liter (mmol/L) Standard Deviation 1.458
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 Week 12	0.38 Millimoles per liter (mmol/L) Standard Deviation 1.612	-1.25 Millimoles per liter (mmol/L) Standard Deviation 1.511	-1.92 Millimoles per liter (mmol/L) Standard Deviation 1.388	-1.06 Millimoles per liter (mmol/L) Standard Deviation 1.555
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 Week 16	0.50 Millimoles per liter (mmol/L) Standard Deviation 2.448	-0.77 Millimoles per liter (mmol/L) Standard Deviation 1.583	-1.92 Millimoles per liter (mmol/L) Standard Deviation 1.667	-0.78 Millimoles per liter (mmol/L) Standard Deviation 1.821

SECONDARY outcome

Timeframe: Baseline; Week 4, Week 8, Week 12, and Week 16

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.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Change From Baseline in Body Weight at Week 4, 8, 12, and 16 Week 4	-0.16 Kilograms Standard Deviation 0.956	-0.36 Kilograms Standard Deviation 0.752	-0.25 Kilograms Standard Deviation 1.268	-0.02 Kilograms Standard Deviation 1.120
Change From Baseline in Body Weight at Week 4, 8, 12, and 16 Week 8	-0.29 Kilograms Standard Deviation 1.289	-0.06 Kilograms Standard Deviation 0.926	-0.46 Kilograms Standard Deviation 1.671	-0.25 Kilograms Standard Deviation 1.684
Change From Baseline in Body Weight at Week 4, 8, 12, and 16 Week 12	-0.43 Kilograms Standard Deviation 1.409	0.09 Kilograms Standard Deviation 1.277	-0.20 Kilograms Standard Deviation 1.906	-0.22 Kilograms Standard Deviation 1.459
Change From Baseline in Body Weight at Week 4, 8, 12, and 16 Week 16	-0.65 Kilograms Standard Deviation 1.715	0.43 Kilograms Standard Deviation 1.468	-0.20 Kilograms Standard Deviation 1.977	-0.08 Kilograms Standard Deviation 1.740

SECONDARY outcome

Timeframe: Week 4, Week 8, Week 12, and Week 16

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

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 Participants Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 Participants Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 Participants Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <6.5%, Week 4	0 Participants	1 Participants	2 Participants	1 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <6.5%, Week 8	0 Participants	5 Participants	15 Participants	5 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <6.5%, Week 12	0 Participants	6 Participants	19 Participants	8 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <6.5%, Week 16	0 Participants	5 Participants	18 Participants	8 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <7%, Week 4	2 Participants	7 Participants	19 Participants	9 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <7%, Week 8	4 Participants	12 Participants	27 Participants	18 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <7%, Week 12	3 Participants	12 Participants	32 Participants	19 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 HbA1c <7%, Week 16	3 Participants	9 Participants	34 Participants	21 Participants

SECONDARY outcome

Timeframe: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24

Population: PK Analysis Population: all participants for whom a PK sample was obtained and analyzed

Clearance is defined as the volume of plasma cleared of albiglutide per unit time. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, pharmacokinetic (PK) samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.

Outcome measures

Outcome measures
Measure	Placebo n=159 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Mean Clearance of Albiglutide	47.8 milliliters per hour Interval 45.7 to 49.9	—	—	—

SECONDARY outcome

Timeframe: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24

Population: PK Analysis Population

Volume of distribution is defined as the apparent volume in which albiglutide is distributed. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.

Outcome measures

Outcome measures
Measure	Placebo n=159 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Mean Volume of Distribution of Albiglutide	9.34 Liters Interval 8.71 to 10.0	—	—	—

SECONDARY outcome

Timeframe: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24

Population: PK Analysis Population (Pop)

Absorption rate is defined as the rate at which albiglutide enters the blood circulation. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.

Outcome measures

Outcome measures
Measure	Placebo n=159 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Mean Absorption Rate of Albiglutide	0.0154 hour^-1 Interval 0.0134 to 0.0183	—	—	—

SECONDARY outcome

Timeframe: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24

Population: PK/PD Analysis Pop: all participants in the PK Analysis Pop with sufficient dosing history for inclusion in the PK/PD analysis. Modeled population PK data (analyzed using a non-linear mixed effect modeling approach) are presented. A one-compartment PK model with first-order absorption/elimination processes was selected to describe GSK716155 PK.

EC50 is defined as the concentration of albiglutide that give a half-maximal HbA1c and FPG response. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. EC50 estimates used PK data as well as HbA1c and FPG efficacy data. EC50 was estimated from an inhibitory Emax (maximal possible effect of albiglutide) model.

Outcome measures

Outcome measures
Measure	Placebo n=157 Participants Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG HbA1c	3360 nanograms per milliliter Interval 2440.0 to 5260.0	—	—	—
Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG FPG	3850 nanograms per milliliter Interval 1420.0 to 6330.0	—	—	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Albiglutide 15 mg Weekly

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Albiglutide 30 mg Weekly

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Albiglutide 30 mg Every Other Week

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=53 participants at risk Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 15 mg Weekly n=52 participants at risk Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Weekly n=54 participants at risk Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.	Albiglutide 30 mg Every Other Week n=53 participants at risk Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion.
Ear and labyrinth disorders Deafness neurosensory	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	1.9% 1/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Ear and labyrinth disorders Vertigo	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	1.9% 1/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	1.9% 1/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	1.9% 1/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Nervous system disorders Carotid artery stenosis	1.9% 1/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Nervous system disorders Cerebral infarction	1.9% 1/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Psychiatric disorders Depression	1.9% 1/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/52 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	1.9% 1/54 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.	0.00% 0/53 • On-therapy serious adverse events (SAEs)/non-serious AEs, with a start date on/after the first day of study medication (SM) and within 56 days after the end of SM, were collected from the start of SM until Follow-up/Early Withdrawal (up to Study Day 168). On-therapy SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all enrolled participants who received at least one dose of study treatment. Participants were analyzed according to treatment received.

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