Last updated: 11/07/2018 04:56:49
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
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Basic Science
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in myocardial glucose utilization as assessed by [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) imaging
Timeframe: Baseline and Week 13
Change from Baseline in myocardial efficiency (work performed/myocardial oxygen consumption [MVO2]) assessed at rest
Timeframe: Baseline and Week 13
Change from Baseline in peak oxygen uptake (peak VO2) as assessed by bicycle cardiopulmonary exercise testing
Timeframe: Baseline and Week 13
Secondary outcomes:
Change from Baseline in left ventricular ejection fraction (LVEF) as assessed by echocardiogram
Timeframe: Baseline and Week 13
Change from Baseline in left ventricular (LV) volumes in systole and diastole as assessed by echocardiogram
Timeframe: 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
Timeframe: 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
Timeframe: Baseline and Week 13
Change from Baseline in LV and RV function assessed by CMR (LV mass), myocardial strain assessed by myocardial tagging indices
Timeframe: Baseline and Week 13
Change from Baseline in cardiac energetics (PCr/ATP) measured by 31P magnetic resonance spectroscopy (MRS)
Timeframe: Baseline and Week 13
Change from Baseline in cardiac and liver fat by proton spectroscopy (1H MRS)
Timeframe: Baseline and Week 13
Change from Baseline in exercise capacity assessed by 6-minute walk test
Timeframe: Baseline and Week 13
Change from Baseline in serum N-terminal fragment brain natriuretic peptide (NT-BNP) level
Timeframe: Change from Baseline at Week 13
Change from Baseline in plasma levels of glucose, and free fatty acids (FFA)
Timeframe: Baseline and Week 13
Change from Baseline in plasma levels of insulin
Timeframe: Baseline and Week 13
Change from Baseline in quality of life as assessed by the minnesota living with heart failure questionnaire
Timeframe: Baseline and Week 13
Number of participants with any adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Baseline and Week 13
Number of participants with adverse events by the indicated severity
Timeframe: Baseline and Week 13
Interventions:
Drug: GSK716155
Drug: Placebo
Enrollment:
82
Observational study model:
Not applicable
Primary completion date:
2012-18-09
Time perspective:
Not applicable
Clinical publications:
John J. Lepore, Eric Olson, Laura Demopoulos, Thomas Haws, Zixing Fang, April Barbour, Michael Fossler, Victor Davila, Stuart D. Russell, Robert Gropler. 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;4(7):559-566
Medical condition
Heart failure, Congestive
Product
albiglutide
Collaborators
Not applicable
Study date(s)
September 2010 to September 2012
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
21 - 75 years
Accepts healthy volunteers
No
- Chronic dilated cardiomyopathy of ischemic or non-ischemic origin
- Clinically stable on optimal therapies for at least 3 months prior to screening/baseline visit.
- 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.
Inclusion and exclusion criteria
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
Trial location(s)
Location
GSK Investigational Site
Detroit, Michigan, United States, 48202
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21287
Status
Study Complete
Location
GSK Investigational Site
Savannah, Georgia, United States, 31405
Status
Study Complete
Location
GSK Investigational Site
St Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Status
Study Complete
Location
GSK Investigational Site
Metairie, Louisiana, United States, 70006
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
New York, Pennsylvania, United States, 10032
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stony Brook, New York, United States, 11794
Status
Study Complete
Location
GSK Investigational Site
Newark, New Jersey, United States, 7103
Status
Study Complete
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55407
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2012-18-09
Actual study completion date
2012-18-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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