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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01357850
• Collaborator: (none)
• Enrollment: 82
• Locations: 15
• Arms: 4
• Actual Duration (Months): 24.1
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This exploratory proof of concept study will be conducted in patients with stable New York Heart Association (NYHA) Class II-III heart failure. The focus of the efficacy endpoints is to test the hypothesis that GSK716155 administration will increase glucose uptake and utilization in the myocardium, resulting in increased myocardial efficiency and increased exercise capacity. A positive result, defined as either statistically significant effects on one or more of the efficacy endpoints or as an overall signal suggesting a clinically relevant effect on myocardial physiology, would provide evidence for potential progression into further development in a chronic heart failure population.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Congestive	Drug: GSK716155; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: Sep 15, 2010
• Actual Primary Completion Date: Sep 18, 2012
• Actual Study Completion Date: Sep 18, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK716155 (3.75mg) GSK716155 (3.75mg)	Drug: GSK716155; GSK716155
Experimental: GSK716155 (15mg) GSK716155 (15mg)	Drug: GSK716155; GSK716155
Experimental: GSK716155 (30mg) GSK716155 (30mg)	Drug: GSK716155; GSK716155
Placebo Comparator: GSK716155-matched placebo GSK716155-matcued placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Myocardial Glucose Utilization as Assessed by [18F]Fluoro-2-deoxy-glucose Positron Emission Tomography (FDG-PET) Imaging [Baseline and Week 13]

   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.

2. Change From Baseline in Myocardial Efficiency (Work Performed/Myocardial Oxygen Consumption [MVO2]) Assessed at Rest [Baseline and Week 13]

   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.

3. Change From Baseline in Peak Oxygen Uptake (Peak VO2) as Assessed by Bicycle Cardiopulmonary Exercise Testing [Baseline and Week 13]

   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.

Secondary Outcome Measures

1. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram [Baseline and Week 13]

   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.

2. Change From Baseline in Left Ventricular (LV) Volumes in Systole and Diastole as Assessed by Echocardiogram [Baseline and Week 13]

   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.

3. Change From Baseline in LV and RV Function Assessed by Cardiac Magnetic Resonance (CMR) (LVEF), Myocardial Strain Assessed by Myocardial Tagging Indices [Baseline and Week 13]

   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.

4. 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 [Baseline and Week 13]

   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.

5. Change From Baseline in LV and RV Function Assessed by CMR (LV Mass), Myocardial Strain Assessed by Myocardial Tagging Indices [Baseline and Week 13]

   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.

6. Change From Baseline in Cardiac Energetics (PCr/ATP) Measured by 31P Magnetic Resonance Spectroscopy (MRS) [Baseline and Week 13]

   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.

7. Change From Baseline in Cardiac and Liver Fat by Proton Spectroscopy (1H MRS) [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.

8. Change From Baseline in Exercise Capacity Assessed by 6-minute Walk Test [Baseline and Week 13]

   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.

9. Change From Baseline in Serum N-terminal Fragment Brain Natriuretic Peptide (NT-BNP) Level [Change from Baseline at Week 13]

   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.

10. Change From Baseline in Plasma Levels of Glucose, and Free Fatty Acids (FFA) [Baseline and Week 13]

    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.

11. Change From Baseline in Plasma Levels of Insulin [Baseline and Week 13]

    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.

12. Change From Baseline in Quality of Life as Assessed by the Minnesota Living With Heart Failure Questionnaire [Baseline and Week 13]

    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.

13. Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline and Week 13]

    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.

14. Number of Participants With Adverse Events by the Indicated Severity [Baseline and Week 13]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic dilated cardiomyopathy of ischemic or non-ischemic origin

• Clinically stable on optimal therapies for at least 3 months prior to screening/baseline visit.

• Left ventricular ejection fraction greater than or equal to 40% as assessed by any measurement in the previous 24 months.

• NYHA Class II/III heart failure for a minimum of 6 months prior to enrolment

• Male or female between 21 and 75 years of age inclusive, at the time of signing the informed consent. However the optimal age range for this study will be 40 to 65 years of age.

• A female subject is eligible to participate if she is of:

Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)

40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].

Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit ~28 days post-last dose.

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

• Confirmed QTcB or QTcF < 480 msec; or QTc < 500 msec in subjects with Bundle Branch Block.

• AST and ALT < 2xULN; alkaline phosphatase and bilirubin greater than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Subjects must be able to perform performance/exercise testing

Exclusion Criteria:

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Active ischemia manifest as a history of myocardial infarction or unstable angina in the past 12 months or a history of coronary revascularization (percutaneous coronary intervention and/or coronary artery bypass grafting) in the past 6 months.

-. High suspicion of active myocardial ischemia, in the opinion of the treating physician

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

• History of drug/alcohol abuse.

• A positive test for HIV antibody.

• Calcitonin > 100 pg./mL

• Triglycerides > 850 mg/dL

• History of significant gastrointestinal surgery, including gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function.

• History of regular alcohol consumption within 6 months of the study defined as:

For UK: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

For US: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Known allergy or history of sensitivity to albiglutide, any other GLP-1 analogue, , or Baker's yeast.

• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.

• Lactating females.

• Unwillingness or inability to follow the procedures outlined in the protocol (e.g.. related to psychiatric disorder)

• Subject is mentally or legally incapacitated.

• Known diagnosis of diabetes mellitus, fasting glucose >140mg/dL, or HbA1c > 7%.

• Uncorrected thyroid disease manifest as an abnormal thyroid-stimulating hormone (TSH) (outside reference range at screening).

• Other medical problems with life expectancy less than 1yr.

• Other causes of cardiomyopathy or left ventricular dysfunction including:

Uncorrected primary obstructive or regurgitant valvular disease Restrictive cardiomyopathy due to amyloidosis, hemochromatosis, sarcoidosis or other cause Cardiac hypertrophy with wall thickness >1.5cm Alcohol-induced cardiomyopathy Women with heart failure during the 12 months following childbirth. Complex congenital heart disease Anthracycline induced cardiomyopathy

• Subjects with genetic disorders of skeletal muscle (e.g. Duchenne muscular dystrophy)

• Clinically significant pericardial disease.

• Listed as a status 1A or 1B on heart transplant waiting list.

• History of deep vein thrombosis or a known coagulation disorder

• History of pancreatitis

• History of or family history of medullary thyroid carcinoma

• History of or family history of multiple endocrine neoplasia type 2

• History of renal dysfunction with estimated GFR < 40 ml/min at screening

• Resting systolic blood pressure < 85 mmHg or >170 mmHg; or diastolic blood pressure

110 mgHg at screening.

• Inability of the patient to lie flat for a combined total of up to 4 hours to complete imaging assessments.

• No subjects will be enrolled at the single site performing the CMR sub-study who have contraindications to MRI scanning including, but not limited to:

Intracranial aneurysm clips with an appropriate operative conformation History of intra- orbital metal fragments Pacemakers or non-MR compatible heart valves Inner ear implants History of claustrophobia deemed significant by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Savannah	Georgia	United States	31405
2	GSK Investigational Site	Metairie	Louisiana	United States	70006
3	GSK Investigational Site	Auburn	Maine	United States	04210
4	GSK Investigational Site	Baltimore	Maryland	United States	21287
5	GSK Investigational Site	Detroit	Michigan	United States	48202
6	GSK Investigational Site	Minneapolis	Minnesota	United States	55407
7	GSK Investigational Site	Saint Louis	Missouri	United States	63110
8	GSK Investigational Site	Newark	New Jersey	United States	7103
9	GSK Investigational Site	Stony Brook	New York	United States	11794
10	GSK Investigational Site	Columbus	Ohio	United States	43210
11	GSK Investigational Site	New York	Pennsylvania	United States	10032
12	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
13	GSK Investigational Site	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
14	GSK Investigational Site	London		United Kingdom	W12 0HS
15	GSK Investigational Site	Oxford		United Kingdom	OX3 9DU

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01357850
• Other Study ID Numbers: 112670
• First Posted: May 23, 2011
• Last Update Posted: Aug 17, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Pre-assignment Detail	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.

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

Baseline Characteristics

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg	Total
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Total of all reporting groups
Overall Participants	30	12	13	27	82
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.6 (9.60)	51.3 (12.44)	57.2 (11.02)	58.2 (10.23)	56.1 (10.53)
Sex: Female, Male (Count of Participants)
Female	9 30%	3 25%	2 15.4%	7 25.9%	21 25.6%
Male	21 70%	9 75%	11 84.6%	20 74.1%	61 74.4%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	3 10%	4 33.3%	5 38.5%	4 14.8%	16 19.5%
Native Hawaiian Or Other Pacific Islander	1 3.3%	0 0%	0 0%	0 0%	1 1.2%
Asian - Central/South Asian Heritage	0 0%	0 0%	0 0%	1 3.7%	1 1.2%
White - White/Caucasian/European Heritage	26 86.7%	7 58.3%	8 61.5%	22 81.5%	63 76.8%
White - Arabic/North African Heritage	0 0%	1 8.3%	0 0%	0 0%	1 1.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Myocardial Glucose Utilization as Assessed by [18F]Fluoro-2-deoxy-glucose Positron Emission Tomography (FDG-PET) Imaging
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	10	4	4	11
Least Squares Mean (95% Confidence Interval) [micromoles per gram per minute]	0.0185	0.0103	0.0369	0.0059

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 3.75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7873
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0119
	Confidence Interval	(2-Sided) 95%; -0.0768 to 0.1005
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 15 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0499
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0678
	Confidence Interval	(2-Sided) 95%; 0.0000 to 0.1356
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1666
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0467
	Confidence Interval	(2-Sided) 95%; -0.0204 to 0.1137
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Myocardial Efficiency (Work Performed/Myocardial Oxygen Consumption [MVO2]) Assessed at Rest
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	10	5	11	11
Least Squares Mean (95% Confidence Interval) [millimeters of mercury/liter/minute2]	-1051.90	-1070.09	-348.58	-870.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 3.75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9343
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	134.89
	Confidence Interval	(2-Sided) 95%; -3172.05 to 3441.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 15 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3375
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1278.77
	Confidence Interval	(2-Sided) 95%; -1398.13 to 3955.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5582
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	772.70
	Confidence Interval	(2-Sided) 95%; -1887.77 to 3433.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline in Peak Oxygen Uptake (Peak VO2) as Assessed by Bicycle Cardiopulmonary Exercise Testing
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	29	12	13	26
Least Squares Mean (95% Confidence Interval) [Milliliters per kilogram per minute]	-0.63	0.05	0.51	0.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 3.75 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2256
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.06
	Confidence Interval	(2-Sided) 95%; -5.43 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 15 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5647
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95%; -4.22 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Albiglutide 30 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8942
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -2.44 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	28	11	13	27
Geometric Mean (Standard Error) [Percentage]	1.12 (1.06)	0.99 (2.21)	1.03 (1.64)	1.08 (1.08)

5. Secondary Outcome

Title	Change From Baseline in Left Ventricular (LV) Volumes in Systole and Diastole as Assessed by Echocardiogram
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	28	11	13	27
LV end-diastolic volume	0.9 (4.92)	1.0 (3.05)	1.0 (4.37)	1.0 (5.54)
LV end-systolic volume	0.9 (4.05)	1.0 (3.80)	1.0 (5.08)	0.9 (5.11)

6. Secondary Outcome

Title	Change From Baseline in LV and RV Function Assessed by Cardiac Magnetic Resonance (CMR) (LVEF), Myocardial Strain Assessed by Myocardial Tagging Indices
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	5	1	2	7
Geometric Mean (Standard Error) [Percentage]	1.17 (1.64)	1.14 (NA)	1.09 (4.0)	1.09 (1.90)

7. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	5	1	2	7
LV end-diastolic volume	0.99 (11.08)	1.02 (NA)	0.96 (12.50)	0.95 (11.79)
LV end-systolic volume	0.90 (7.80)	0.89 (NA)	0.94 (3.00)	0.89 (9.42)

8. Secondary Outcome

Title	Change From Baseline in LV and RV Function Assessed by CMR (LV Mass), Myocardial Strain Assessed by Myocardial Tagging Indices
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	5	1	2	7
Geometric Mean (Standard Error) [Grams]	0.96 (7.99)	1.04 (NA)	1.08 (1.50)	0.97 (10.65)

9. Secondary Outcome

Title	Change From Baseline in Cardiac Energetics (PCr/ATP) Measured by 31P Magnetic Resonance Spectroscopy (MRS)
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	5	6
Least Squares Mean (95% Confidence Interval) [ratio]	0.33	0.11

10. Secondary Outcome

Title	Change From Baseline in Cardiac and Liver Fat by Proton Spectroscopy (1H MRS)
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	0	0	0	0

11. Secondary Outcome

Title	Change From Baseline in Exercise Capacity Assessed by 6-minute Walk Test
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	28	12	13	27
Geometric Mean (95% Confidence Interval) [Meters]	1.03	1.10	1.14	1.05

12. Secondary Outcome

Title	Change From Baseline in Serum N-terminal Fragment Brain Natriuretic Peptide (NT-BNP) Level
Description	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.
Time Frame	Change from Baseline at Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	28	12	12	25
Geometric Mean (Standard Error) [Nanogram per liter]	0.90 (10.43)	0.90 (34.20)	0.70 (31.50)	0.90 (25.73)

13. Secondary Outcome

Title	Change From Baseline in Plasma Levels of Glucose, and Free Fatty Acids (FFA)
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	30	12	13	27
FFA (n=24, 10, 12, 22)	0.81 (0.03)	0.90 (0.05)	0.74 (0.04)	0.87 (0.05)
Glucose (n=29, 12, 13, 27)	1.01 (0.14)	0.91 (0.27)	1.00 (0.16)	1.00 (0.17)

14. Secondary Outcome

Title	Change From Baseline in Plasma Levels of Insulin
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	28	12	13	26
Geometric Mean (Standard Error) [picomole per liter (pmol/L)]	0.9 (18.08)	0.7 (30.49)	1.0 (15.41)	1.2 (15.56)

15. Secondary Outcome

Title	Change From Baseline in Quality of Life as Assessed by the Minnesota Living With Heart Failure Questionnaire
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	29	12	13	27
Geometric Mean (95% Confidence Interval) [Scores on a scale]	0.8	0.7	0.7	0.7

16. Secondary Outcome

Title	Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	30	12	13	27
Any AE	25 83.3%	12 100%	12 92.3%	20 74.1%
Any SAEs	4 13.3%	2 16.7%	2 15.4%	0 0%

17. Secondary Outcome

Title	Number of Participants With Adverse Events by the Indicated Severity
Description	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.
Time Frame	Baseline and Week 13

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Albiglutide 3.75 mg	Albiglutide 15 mg	Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.	Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
Measure Participants	30	12	13	27
Mild	10 33.3%	6 50%	4 30.8%	12 44.4%
Moderate	13 43.3%	4 33.3%	6 46.2%	6 22.2%
Severe	2 6.7%	2 16.7%	2 15.4%	2 7.4%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		Albiglutide 3.75 mg		Albiglutide 15 mg		Albiglutide 30 mg
Arm/Group Description	Participants received albiglutide matching placebo weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.		Participants received albiglutide 3.75 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.		Participants received albiglutide 15 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.		Participants received albiglutide 30 mg weekly injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen.
All Cause Mortality
	Placebo		Albiglutide 3.75 mg		Albiglutide 15 mg		Albiglutide 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Albiglutide 3.75 mg		Albiglutide 15 mg		Albiglutide 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)		2/12 (16.7%)		2/13 (15.4%)		0/27 (0%)
Cardiac disorders
Atrial Fibrillation	1/30 (3.3%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Cardiac Failure Congestive	1/30 (3.3%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Ventricular Tachycardia	1/30 (3.3%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Gastrointestinal disorders
Small Intestinal Obstruction	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
General disorders
Device Malfunction	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Infections and infestations
Urinary Tract Infection	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Injury, poisoning and procedural complications
Procedural Vomiting	1/30 (3.3%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Metabolism and nutrition disorders
Dehydration	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Vascular disorders
Hypotension	0/30 (0%)		1/12 (8.3%)		1/13 (7.7%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Albiglutide 3.75 mg		Albiglutide 15 mg		Albiglutide 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/30 (73.3%)		11/12 (91.7%)		11/13 (84.6%)		19/27 (70.4%)
Blood and lymphatic system disorders
Anaemia	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Eosinophilia	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Thrombocytopenia	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Cardiac disorders
Palpitations	1/30 (3.3%)		1/12 (8.3%)		0/13 (0%)		1/27 (3.7%)
Cardiac failure	2/30 (6.7%)		2/12 (16.7%)		2/13 (15.4%)		0/27 (0%)
Angina pectoris	0/30 (0%)		0/12 (0%)		2/13 (15.4%)		0/27 (0%)
Atrial fibrillation	0/30 (0%)		2/12 (16.7%)		0/13 (0%)		0/27 (0%)
Ventricular tachycardia	1/30 (3.3%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Ventricular extrasystoles	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Eye disorders
Dry eye	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Vision blurred	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Gastrointestinal disorders
Diarrhoea	5/30 (16.7%)		2/12 (16.7%)		3/13 (23.1%)		4/27 (14.8%)
Vomiting	3/30 (10%)		0/12 (0%)		1/13 (7.7%)		2/27 (7.4%)
Constipation	1/30 (3.3%)		0/12 (0%)		1/13 (7.7%)		2/27 (7.4%)
Abdominal discomfort	0/30 (0%)		0/12 (0%)		0/13 (0%)		2/27 (7.4%)
Abdominal pain	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		1/27 (3.7%)
Nausea	3/30 (10%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Abdominal pain upper	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
General disorders
Fatigue	1/30 (3.3%)		2/12 (16.7%)		0/13 (0%)		2/27 (7.4%)
Injection site pruritus	1/30 (3.3%)		1/12 (8.3%)		0/13 (0%)		1/27 (3.7%)
Injection site haematoma	1/30 (3.3%)		2/12 (16.7%)		2/13 (15.4%)		0/27 (0%)
Injection site pain	2/30 (6.7%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Implant site pain	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Immune system disorders
Seasonal allergy	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Infections and infestations
Upper respiratory tract infection	4/30 (13.3%)		2/12 (16.7%)		1/13 (7.7%)		2/27 (7.4%)
Nasopharyngitis	3/30 (10%)		1/12 (8.3%)		0/13 (0%)		1/27 (3.7%)
Ear infection	0/30 (0%)		2/12 (16.7%)		0/13 (0%)		0/27 (0%)
Eye infection	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Respiratory tract infection	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Subcutaneous abscess	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Urinary tract infection	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Vulvovaginal mycotic infection	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Injury, poisoning and procedural complications
Contusion	0/30 (0%)		0/12 (0%)		0/13 (0%)		3/27 (11.1%)
Excoriation	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Investigations
Blood creatinine increased	1/30 (3.3%)		0/12 (0%)		0/13 (0%)		3/27 (11.1%)
Lipase increased	0/30 (0%)		0/12 (0%)		0/13 (0%)		3/27 (11.1%)
Blood urea increased	1/30 (3.3%)		1/12 (8.3%)		0/13 (0%)		2/27 (7.4%)
International normalised ratio increased	1/30 (3.3%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Brain natriuretic peptide increased	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Metabolism and nutrition disorders
Impaired fasting glucose	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		2/27 (7.4%)
Gout	1/30 (3.3%)		1/12 (8.3%)		1/13 (7.7%)		0/27 (0%)
Increased appetite	2/30 (6.7%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/30 (0%)		2/12 (16.7%)		0/13 (0%)		2/27 (7.4%)
Musculoskeletal pain	2/30 (6.7%)		0/12 (0%)		1/13 (7.7%)		1/27 (3.7%)
Muscle spasms	1/30 (3.3%)		0/12 (0%)		1/13 (7.7%)		1/27 (3.7%)
Back pain	1/30 (3.3%)		1/12 (8.3%)		2/13 (15.4%)		0/27 (0%)
Musculoskeletal discomfort	2/30 (6.7%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Musculoskeletal chest pain	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Osteopenia	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Nervous system disorders
Dizziness	2/30 (6.7%)		2/12 (16.7%)		1/13 (7.7%)		2/27 (7.4%)
Headache	2/30 (6.7%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Presyncope	2/30 (6.7%)		0/12 (0%)		0/13 (0%)		0/27 (0%)
Paraesthesia	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Transient ischaemic attack	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Psychiatric disorders
Anxiety	1/30 (3.3%)		1/12 (8.3%)		1/13 (7.7%)		0/27 (0%)
Insomnia	2/30 (6.7%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Renal and urinary disorders
Renal failure acute	0/30 (0%)		1/12 (8.3%)		1/13 (7.7%)		0/27 (0%)
Reproductive system and breast disorders
Breast tenderness	1/30 (3.3%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/30 (0%)		0/12 (0%)		0/13 (0%)		2/27 (7.4%)
Oropharyngeal pain	0/30 (0%)		0/12 (0%)		0/13 (0%)		2/27 (7.4%)
Dyspnoea	2/30 (6.7%)		0/12 (0%)		2/13 (15.4%)		1/27 (3.7%)
Dyspnoea paroxysmal nocturnal	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Hypoventilation	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Rales	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Rhinitis allergic	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Sinus congestion	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Wheezing	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Acne	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Acne cystic	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Actinic keratosis	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Hyperhidrosis	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Pruritus	0/30 (0%)		0/12 (0%)		1/13 (7.7%)		0/27 (0%)
Rash papular	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Seborrhoeic dermatitis	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Vascular disorders
Hypotension	2/30 (6.7%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)
Hot flush	0/30 (0%)		1/12 (8.3%)		0/13 (0%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.