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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01357850
First received: November 11, 2010
Last updated: August 29, 2013
Last verified: August 2013

November 11, 2010
August 29, 2013
September 2010
August 2012   (final data collection date for primary outcome measure)
  • Myocardial glucose utilization as assessed by FDG-PET imaging [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Myocardial efficiency (work performed/MVO2) assessed at rest: a.) Work calculated by cardiac echo and b.)b. MVO2 accessed via 11C-acetate PET imaging [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Peak oxygen uptake (VO2 max) as assessed by bicycle cardiopulmonary exercise testing [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01357850 on ClinicalTrials.gov Archive Site
  • Left ventricular function (LVEF, LV volumes in systole and diastole) as assessed by echocardiogram [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Exercise capacity assessed by 6-minute walk test [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Serum NT-BNP level [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Plasma levels of glucose, insulin, free fatty acids; HOMA index [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Safety endpoints including but not limited to: a.) incidence and severity of AEs b.) all cause mortality c.) hospitalization for heart failure [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Exploratory PK parameters may be measured including (but not limited to) AUC, CMAX and Ct. [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Cardiac energetics (PCr/ATP) measured by 31P MRS [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Cardiac and liver fat by proton spectroscopy (1H MRS) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Left ventricular function (LVEF, LV volumes in systole and diastole) as assessed by echocardiogram [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • LV and RV function assessed by CMR (LVEF, LV and RV volumes in systole and diastole, LV mass), myocardial strain assessed by myocardial tagging indicies [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Exercise capacity assessed by 6-minute walk test [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Serum NT-BNP level [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Plasma levels of glucose, insulin, free fatty acids; HOMA index [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Safety endpoints including but not limited to: a.) incidence and severity of AEs b.) all cause mortality c.) hospitalization for heart failure [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Exploratory PK parameters may be measured including (but not limited to) AUC, CMAX and Ct. [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Cardiac energetics (PCr/ATP) measured by 31P MRS [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Cardiac and liver fat by proton spectroscopy (1H MRS) [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Heart Failure, Congestive
  • Drug: GSK716155
    GSK716155
  • Drug: Placebo
    Placebo
  • Experimental: GSK716155 (3.75mg)
    GSK716155 (3.75mg)
    Intervention: Drug: GSK716155
  • Experimental: GSK716155 (15mg)
    GSK716155 (15mg)
    Intervention: Drug: GSK716155
  • Experimental: GSK716155 (30mg)
    GSK716155 (30mg)
    Intervention: Drug: GSK716155
  • Placebo Comparator: GSK716155-matched placebo
    GSK716155-matcued placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
August 2012
August 2012   (final data collection date for primary outcome measure)

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

Both
21 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   United Kingdom
 
NCT01357850
112670
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP