Trial Outcomes & Findings for A Multi-center, Placebo-controlled Study to Evaluate the Safety of GSK716155 and Its Effects on Myocardial Metabolism, Myocardial Function, and Exercise Capacity in Patients With NYHA Class II/III Congestive Heart Failure (NCT NCT01357850)

Last Updated: 2017-08-17

Results Overview

FDG-PET imaging was performed at Baseline and Week 13 to assess myocardial glucose uptake. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on analysis using a mixed effects analysis of variance (ANOVA) model, fitting terms for treatment, visit and interaction of treatment and visit, with participants as random effects.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

Baseline and Week 13

Results posted on

2017-08-17

Participant Flow

Participants (par.) who met eligibility criteria and completed a 30 day Screening were then randomized to a 13-week Treatment Period, followed by a Follow-up visit 28 days post-treatment. The duration of the study was approximately 20 weeks from Screening to Follow-up. A total of 100 par. were planned, and 82 par. were randomized.

Participant milestones

Participant milestones
Measure	Placebo Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg Participants received albiglutide 3.75 milligrams (mg) weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Overall Study STARTED	30	12	13	27
Overall Study COMPLETED	29	12	13	27
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg Participants received albiglutide 3.75 milligrams (mg) weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Overall Study Lost to Follow-up	1	0	0	0

Baseline Characteristics

A Multi-center, Placebo-controlled Study to Evaluate the Safety of GSK716155 and Its Effects on Myocardial Metabolism, Myocardial Function, and Exercise Capacity in Patients With NYHA Class II/III Congestive Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=30 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Total n=82 Participants Total of all reporting groups
Age, Continuous	55.6 Years STANDARD_DEVIATION 9.60 • n=5 Participants	51.3 Years STANDARD_DEVIATION 12.44 • n=7 Participants	57.2 Years STANDARD_DEVIATION 11.02 • n=5 Participants	58.2 Years STANDARD_DEVIATION 10.23 • n=4 Participants	56.1 Years STANDARD_DEVIATION 10.53 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	20 Participants n=4 Participants	61 Participants n=21 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	26 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants	63 Participants n=21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 13

Population: Intent-to-Treat (ITT) Population: all randomized participants who received \>= 1 dose of study medication and had \>= 1 on treatment assessment. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=4 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=4 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=11 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Myocardial Glucose Utilization as Assessed by [18F]Fluoro-2-deoxy-glucose Positron Emission Tomography (FDG-PET) Imaging	0.0185 micromoles per gram per minute Interval -0.0158 to 0.0528	0.0103 micromoles per gram per minute Interval -0.044 to 0.0646	0.0369 micromoles per gram per minute Interval 0.0042 to 0.0695	0.0059 micromoles per gram per minute Interval -0.0268 to 0.0386

PRIMARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

MVO2 was estimated by measuring the rate of myocardial clearance of 11C-activity which represents overall myocardial oxidative flux through the TCA cycle. Cardiac work was measured by echocardiography and cardiac efficiency index was calculated as work (by echocardiography) divided by MVO2. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on analysis using a mixed effects ANOVA model, fitting terms for treatment, visit and interaction of treatment and visit, with participants as random effects.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=5 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=11 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=11 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Myocardial Efficiency (Work Performed/Myocardial Oxygen Consumption [MVO2]) Assessed at Rest	-1051.90 millimeters of mercury/liter/minute2 Interval -3136.43 to 1032.63	-1070.09 millimeters of mercury/liter/minute2 Interval -3846.14 to 1705.95	-348.58 millimeters of mercury/liter/minute2 Interval -2278.39 to 1581.23	-870.64 millimeters of mercury/liter/minute2 Interval -2771.39 to 1030.11

PRIMARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Peak VO2 was measured at Baseline and Week 13. Participants performed a maximal exercise test limited by dyspnea or fatigue on a cycle ergometer. After a rest period, the workloads were increased in a step fashion by 25 watts every 3 minutes. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on analysis using a mixed effects ANOVA model, fitting terms for treatment, visit and interaction of treatment and visit, with participants as random effects.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=26 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Peak Oxygen Uptake (Peak VO2) as Assessed by Bicycle Cardiopulmonary Exercise Testing	-0.63 Milliliters per kilogram per minute Interval -1.53 to 0.27	0.05 Milliliters per kilogram per minute Interval -1.35 to 1.45	0.51 Milliliters per kilogram per minute Interval -0.84 to 1.85	0.88 Milliliters per kilogram per minute Interval -0.07 to 1.83

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Echocardiography was performed at Baseline and Week 13 using pulse-wave, continuous-wave, and tissue Doppler. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=11 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram	1.12 Percentage Standard Error 1.06	0.99 Percentage Standard Error 2.21	1.03 Percentage Standard Error 1.64	1.08 Percentage Standard Error 1.08

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Echocardiography was performed at Baseline and Week 13 using pulse-wave, continuous-wave and tissue Doppler. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=11 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Left Ventricular (LV) Volumes in Systole and Diastole as Assessed by Echocardiogram LV end-systolic volume	0.9 Milliliters Standard Error 4.05	1.0 Milliliters Standard Error 3.80	1.0 Milliliters Standard Error 5.08	0.9 Milliliters Standard Error 5.11
Change From Baseline in Left Ventricular (LV) Volumes in Systole and Diastole as Assessed by Echocardiogram LV end-diastolic volume	0.9 Milliliters Standard Error 4.92	1.0 Milliliters Standard Error 3.05	1.0 Milliliters Standard Error 4.37	1.0 Milliliters Standard Error 5.54

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: CMR Substudy Population: all randomized participants who participated in the CMR substudy and had valid Baseline and/or Week 13 assessments for \>= 1 one of the imaging parameters of LV and RV function assessed by CMR (LVEF, LV and RV volumes in systole and diastole, LV mass), myocardial strain assessed by myocardial tagging indices.

Non-contrast CMR to assess left ventricular (LV) and right ventricular (RV) ejection fraction, volume, mass, and strain was performed following a period of rest after exercise testing at Baseline and after the Week 13 treatment phase. A 3Tesla magnetic resonance imagine (MRI) examination was performed including sequences for evaluation of LV structure and function. Only those participants available at the specified time points were analyzed. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=1 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=2 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=7 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in LV and RV Function Assessed by Cardiac Magnetic Resonance (CMR) (LVEF), Myocardial Strain Assessed by Myocardial Tagging Indices	1.17 Percentage Standard Error 1.64	1.14 Percentage Standard Error NA Only one participant was analyzed in this treatment arm at this time point; therefore the mean and standard error cannot be calculated.	1.09 Percentage Standard Error 4.0	1.09 Percentage Standard Error 1.90

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: CMR Substudy Population. Only those participants available at the specified time points were analyzed.

Non-contrast CMR to assess LV and RV ejection fraction, volume, mass, and strain was performed following a period of rest after exercise testing at Baseline and after the Week 13 treatment phase. A 3Tesla magnetic resonance imagine (MRI) examination was performed including sequences for evaluation of LV structure and function. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=1 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=2 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=7 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in LV and RV Function Assessed by CMR (LV and RV Volumes in Systole and Diastole), Myocardial Strain Assessed by Myocardial Tagging Indices LV end-diastolic volume	0.99 Milliliters Standard Error 11.08	1.02 Milliliters Standard Error NA Only one participant was analyzed in this treatment arm at this time point; therefore the mean and standard error cannot be calculated.	0.96 Milliliters Standard Error 12.50	0.95 Milliliters Standard Error 11.79
Change From Baseline in LV and RV Function Assessed by CMR (LV and RV Volumes in Systole and Diastole), Myocardial Strain Assessed by Myocardial Tagging Indices LV end-systolic volume	0.90 Milliliters Standard Error 7.80	0.89 Milliliters Standard Error NA Only one participant was analyzed in this treatment arm at this time point; therefore the mean and standard error cannot be calculated.	0.94 Milliliters Standard Error 3.00	0.89 Milliliters Standard Error 9.42

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: CMR Substudy Population. Only those participants available at the specified time points were analyzed.

Non-contrast CMR to assess left/right ventricular ejection fraction, volume, mass, and strain was performed following a period of rest after exercise testing at Baseline and after the Week 13 treatment phase. A 3Tesla magnetic resonance imagine (MRI) examination was performed including sequences for evaluation of LV structure and function. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=1 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=2 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=7 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in LV and RV Function Assessed by CMR (LV Mass), Myocardial Strain Assessed by Myocardial Tagging Indices	0.96 Grams Standard Error 7.99	1.04 Grams Standard Error NA Only one participant was analyzed in this treatment arm at this time point; therefore the mean and standard error cannot be calculated.	1.08 Grams Standard Error 1.50	0.97 Grams Standard Error 10.65

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Magnetic Resonance Substudy Population (MRS): all randomized participants who participated in the MRS substudy and had valid Baseline and/or Week 13 assessments for either PCr/ATP via 31P MRS. Only those participants available at the specified time points were analyzed.

Participants underwent a CMR scan performed on a 3 Tesla MR system at Baseline and Week 13 to assess cardiac mass, volumes (global function and dilatation), strain and torsion, cardiac and liver lipid content and cardiac energy metabolism. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=6 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Cardiac Energetics (PCr/ATP) Measured by 31P Magnetic Resonance Spectroscopy (MRS)	0.33 ratio Interval -0.29 to 0.94	0.11 ratio Interval -0.45 to 0.67	—	—

SECONDARY outcome

Timeframe: Baseline and Week 13

Change in Baseline in cardiac and liver fat by proton spectroscopy was planned at Baseline and Week 13. The protocol allowed for sites to perform all or only efficacy assessments, depending on site designation, capability and feasibility. No sites that enrolled participants into this study were able to perform this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The six minute walk test was performed at Baseline and Week 13. All participantss were given standardized instructions and the distance walked was measured. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Exercise Capacity Assessed by 6-minute Walk Test	1.03 Meters Interval 0.98 to 1.07	1.10 Meters Interval 0.96 to 1.25	1.14 Meters Interval 1.0 to 1.3	1.05 Meters Interval 1.0 to 1.1

SECONDARY outcome

Timeframe: Change from Baseline at Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Baseline is defined as the last available assessment on or prior to the first dose of study medication. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=12 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=25 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Serum N-terminal Fragment Brain Natriuretic Peptide (NT-BNP) Level	0.90 Nanogram per liter Standard Error 10.43	0.90 Nanogram per liter Standard Error 34.20	0.70 Nanogram per liter Standard Error 31.50	0.90 Nanogram per liter Standard Error 25.73

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters at different time points, so the overall number of participants analyzed reflects everyone in the ITT population.

Blood samples for biomarker analysis of fasting levels of glucose and FFA were collected at Weeks 1, 7 and 13; glucose was also collected at Weeks 2, 4, 6, 8, 10, and 12. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Plasma Levels of Glucose, and Free Fatty Acids (FFA) FFA (n=24, 10, 12, 22)	0.81 Millimole per liter (mmol/L) Standard Error 0.03	0.90 Millimole per liter (mmol/L) Standard Error 0.05	0.74 Millimole per liter (mmol/L) Standard Error 0.04	0.87 Millimole per liter (mmol/L) Standard Error 0.05
Change From Baseline in Plasma Levels of Glucose, and Free Fatty Acids (FFA) Glucose (n=29, 12, 13, 27)	1.01 Millimole per liter (mmol/L) Standard Error 0.14	0.91 Millimole per liter (mmol/L) Standard Error 0.27	1.00 Millimole per liter (mmol/L) Standard Error 0.16	1.00 Millimole per liter (mmol/L) Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Blood samples for biomarker analysis of fasting levels of insulin were collected at Weeks 1, 7 and 13. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=26 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Plasma Levels of Insulin	0.9 picomole per liter (pmol/L) Standard Error 18.08	0.7 picomole per liter (pmol/L) Standard Error 30.49	1.0 picomole per liter (pmol/L) Standard Error 15.41	1.2 picomole per liter (pmol/L) Standard Error 15.56

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Minnesota living with heart failure questionnaire (MLHFQ) is a validated instrument to measure participant-reported quality of life at Baseline and Week 13. For each of 21 items, participants rated the effects of heart failure and its treatment on physical, socioeconomic and psychological aspects of their life. To measure the effects of symptoms, functional limitations, psychological distress on an individual's quality of life, the MLHF questionnaire asks each participant to indicate their response using a 6-point scale (ranging from 0 to 5, 0=no, 1=very little, and 5=very much). The min and max scores can range from 0 to 105. The likert scale measures the effect of heart failure and treatments for heart failure on an individual's ability to live as they want. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Change From Baseline in Quality of Life as Assessed by the Minnesota Living With Heart Failure Questionnaire	0.8 Scores on a scale Interval 0.6 to 1.0	0.7 Scores on a scale Interval 0.4 to 1.2	0.7 Scores on a scale Interval 0.5 to 1.0	0.7 Scores on a scale Interval 0.5 to 0.9

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: All Subject Population: all randomized participants who received \>= 1 dose of study medication. Only those participants available at the specified time points were analyzed.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Please refer to the AE/SAE section for further details.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	25 Participants	12 Participants	12 Participants	20 Participants
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	4 Participants	2 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Severity categories: Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities;Moderate: an event that was sufficiently discomforting to interfere with normal everyday activities; Severe: an event that prevents normal everyday activities.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 Participants Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 Participants Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 Participants Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Number of Participants With Adverse Events by the Indicated Severity Mild	10 Participants	6 Participants	4 Participants	12 Participants
Number of Participants With Adverse Events by the Indicated Severity Moderate	13 Participants	4 Participants	6 Participants	6 Participants
Number of Participants With Adverse Events by the Indicated Severity Severe	2 Participants	2 Participants	2 Participants	2 Participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Albiglutide 3.75 mg

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Albiglutide 15 mg

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Albiglutide 30 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=30 participants at risk Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 3.75 mg n=12 participants at risk Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 15 mg n=13 participants at risk Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Albiglutide 30 mg n=27 participants at risk Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Cardiac disorders Atrial Fibrillation	3.3% 1/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Cardiac disorders Cardiac Failure Congestive	3.3% 1/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Cardiac disorders Ventricular Tachycardia	3.3% 1/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Vascular disorders Hypotension	0.00% 0/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	8.3% 1/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	7.7% 1/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	8.3% 1/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
General disorders Device Malfunction	0.00% 0/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	8.3% 1/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Infections and infestations Urinary Tract Infection	0.00% 0/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	7.7% 1/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Injury, poisoning and procedural complications Procedural Vomiting	3.3% 1/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.
Metabolism and nutrition disorders Dehydration	0.00% 0/30 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/12 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	7.7% 1/13 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.	0.00% 0/27 • Serious adverse events (SAEs) and non-serious AEs collected from the start of study medication and within 30 days after the end of study medication (Week 13) are reported. AEs and non-serious AEs are reported for members of the All subjects Population, comprised of all participants randomized to treatment, who have taken at least one dose of study medication.

Other adverse events

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

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