GS-6615 in Adults With Chronic Stable Angina and Coronary Artery Disease

Study Overview
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Brief Summary
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This study will evaluate the effect of GS-6615 in adults with chronic stable angina and coronary artery disease (CAD) receiving a stable daily dose of up to 2 antianginal medications. The study will consist of two periods: a 1 to 3 week Qualifying Period and a Treatment Period lasting 13 days (± 3 days). During the Qualifying Period and at the end of the Treatment Period, participants will undergo exercise tolerance testing.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Study of GS-6615 in Subjects With Chronic Stable Angina and Coronary Artery Disease

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Drug: GS-6615
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to perform a standardized treadmill exercise protocol At least a 3 month history of chronic stable angina triggered by physical effort and relieved by rest and/or short-acting nitroglycerin Coronary artery disease (CAD) documented by one or more of the following: Angiographic evidence (either invasive or noninvasive) of ≥ 50% stenosis of one or more major coronary arteries History of myocardial infarction (MI) documented by positive creatine kinase-myocardial band (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes Noninvasive imaging stress test diagnostic of CAD (eg, nuclear perfusion scan, stress echocardiogram, stress cardiac magnetic resonance scan) Stable antianginal treatment with up to 2 antianginal agents Exclusion Criteria: Inability to exercise or having exercise limitation due to other co-morbidities that may interfere with ability to perform required exercise tolerance testing (ETT) Presence of electrocardiographic or other abnormalities that interfere with ECG interpretation or may cause a false positive stress test History of heart failure as defined by New York Heart Association Class III-IV and/or known left ventricular ejection fraction ≤ 45% History of severe disabling angina as defined by Canadian Cardiovascular Society Class IV Myocardial infarction, acute coronary syndrome or coronary revascularization within 3 months prior to screening, or planned coronary revascularization during the study period Stroke or transient ischemic attack within 6 months prior to screening Chronic persistent atrial fibrillation Uncontrolled hypertension (seated systolic blood pressure (SBP) > 160 mm Hg or diastolic blood pressure (DBP) > 110 mm Hg) Body mass index (BMI) ≥ 36 kg/m^2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS-6615<br>GS-6615 30 mg (5 x 6 mg) on Day 1, followed by 6 mg twice daily | Drug: GS-6615<br>* GS-6615 tablets administered orally<br>|
| Placebo Comparator: Placebo<br>Placebo to match GS-6615 (5 tablets) on Day 1, followed by placebo to match GS-6615 twice daily | Drug: Placebo<br>* Placebo to match GS-6615 tablets administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in time to 1 mm ST-segment depression | For treadmill-related endpoints, baseline is defined as the value derived from the last exercise tolerance testing performed during the qualifying period. | Baseline; Day 13 (± 3 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in total exercise duration at the end of the double-blind treatment period |  | Baseline; Day 13 (± 3 days) | 
| Time to onset of angina during exercise tolerance testing at the end of the double-blind treatment period |  | Baseline; Day 13 (± 3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GS-6615, coronary heart disease, angina pectoris, late sodium current, myocardial ischemia, coronary artery disease, chronic stable angina