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



Status:Completed
Conditions:Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases
Healthy:No
Age Range:Any
Updated:11/18/2012
Start Date:September 2010
End Date:November 2011
Contact:US GSK Clinical Trials Call Center
Email:GSKClinicalSupportHD@gsk.com
Phone:877-379-3718

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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.


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
We found this trial at
11
sites
Grand Rapids, Michigan 49546
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Baton Rouge, Louisiana 70809
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Baton Rouge, LA
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Bethesda, Maryland 20892
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Cherry Hill, New Jersey 08003
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Cherry Hill, NJ
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Chesterfield, Missouri 63017
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Chesterfield, MO
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Cincinnati, Ohio 45229
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Cincinnati, OH
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New York, New York 10032
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New York, NY
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Philadelphia, Pennsylvania 19104
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Philadelphia, PA
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Portland, Maine 04101
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Portland, ME
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Rochester, Minnesota 55905
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Rochester, MN
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Roswell, Georgia 30076
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Roswell, GA
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