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

NCT01357850 | Completed Phase 2 Results

• 1 other identifier: 112670
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 15

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.

Conditions

Heart Failure, Congestive

Outcome Measures

Primary Outcomes (3)

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

  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.

  Baseline and Week 13

• Change From Baseline in Myocardial Efficiency (Work Performed/Myocardial Oxygen Consumption [MVO2]) Assessed at Rest

  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.

  Baseline and Week 13

• Change From Baseline in Peak Oxygen Uptake (Peak VO2) as Assessed by Bicycle Cardiopulmonary Exercise Testing

  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.

  Baseline and Week 13

Secondary Outcomes (14)

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram

  Baseline and Week 13

• Change From Baseline in Left Ventricular (LV) Volumes in Systole and Diastole as Assessed by Echocardiogram

  Baseline and Week 13

• 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

• 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

• Change From Baseline in LV and RV Function Assessed by CMR (LV Mass), Myocardial Strain Assessed by Myocardial Tagging Indices

  Baseline and Week 13

Study Arms (4)

GSK716155 (3.75mg)

EXPERIMENTAL

GSK716155 (3.75mg)

Drug: GSK716155

GSK716155 (15mg)

EXPERIMENTAL

GSK716155 (15mg)

Drug: GSK716155

GSK716155 (30mg)

EXPERIMENTAL

GSK716155 (30mg)

Drug: GSK716155

GSK716155-matched placebo

PLACEBO COMPARATOR

GSK716155-matcued placebo

Drug: Placebo

Interventions

GSK716155 DRUG

GSK716155

GSK716155 (15mg); GSK716155 (3.75mg); GSK716155 (30mg)

Placebo DRUG

Placebo

GSK716155-matched placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Savannah, Georgia, 31405, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Auburn, Maine, 04210, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21287, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55407, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Newark, New Jersey, 7103, United States

Location

GSK Investigational Site

Stony Brook, New York, 11794, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

New York, Pennsylvania, 10032, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

London, W12 0HS, United Kingdom

Location

GSK Investigational Site

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (1)

• Lepore JJ, Olson E, Demopoulos L, Haws T, Fang Z, Barbour AM, Fossler M, Davila-Roman VG, Russell SD, Gropler RJ. Effects of the Novel Long-Acting GLP-1 Agonist, Albiglutide, on Cardiac Function, Cardiac Metabolism, and Exercise Capacity in Patients With Chronic Heart Failure and Reduced Ejection Fraction. JACC Heart Fail. 2016 Jul;4(7):559-566. doi: 10.1016/j.jchf.2016.01.008. Epub 2016 Mar 30.

  PMID: 27039125 DERIVED

Related Links

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

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2010
• First Posted: May 23, 2011
• Study Start: September 15, 2010
• Primary Completion: September 18, 2012
• Study Completion: September 18, 2012
• Last Updated: August 17, 2017
• Results First Posted: October 1, 2014

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); US (12)