A randomized, double-blind, placebo-controlled, cross-over trial looking at the effects of ranolazine on blood flow in the heart as assessed by nuclear imaging.

• Conditions: Coronary artery disease; MedDRA version: 14.0Level: PTClassification code 10011078Term: Coronary artery diseaseSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2011-001516-54-CZ
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-20
• Last Update Posted: 14 April 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 214

Inclusion Criteria

1. Written informed consent
2. Males and females aged = 18 years
3. Able to perform exercise stress testing (either a treadmill ETT or upright cycle
ergometry)
4. Clinically indicated exercise SPECT MPI (stress and rest scans) performed within 4 weeks of screening
5. At least 10% reversible myocardial ischemia on clinically indicated exercise SPECT MPI study as confirmed by the core nuclear laboratory
6. Stable doses of = 2 antianginal medications (not including short-acting nitroglycerin).
The doses of the antianginal medications should not have changed since the qualifying
scans were conducted.
7. Females of childbearing potential must agree to utilize highly effective contraception
methods from screening throughout the duration of study treatment and for 14 days
following the last dose of study drug.
— Female subjects who utilize hormonal contraceptive as 1 of their birth control
methods must have used the same method for at least 3 months prior to study dosing
— Female subjects who have stopped menstruating, must have had 1 of the following to document menopause:
1. Appropriate medical documentation of prior complete bilateral oophorectomy
(i.e., surgical removal of the ovaries, resulting in surgical menopause” and
occurring at the age at which the procedure was performed), or
2. Permanent cessation of previously occurring menses as a result of ovarian failure
(i.e., spontaneous menopause,” which occurs in the United States at a mean age
of 51.5 years).
a) In subjects = 54 years of age, menopause is defined as having a last menstrual
period that occurred = 12 months prior to enrollment into the study and a
follicle-stimulating hormone (FSH) level elevated to within the postmenopausal range based on the laboratory reference range where the hormonal assay is performed;
b) In subjects < 54 years of age, menopause is defined as the absence of normal
menses associated with a negative serum or urine human chorionic gonadotropin (hCG) with concurrently elevated serum FSH level in the postmenopausal range, depressed estradiol (E2) level in the post menopausal range, and absent serum progesterone level, based on the laboratory reference ranges where the hormonal assays are performed
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 107
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 107

Exclusion Criteria

General
1. Unwilling or unable to provide informed consent
2. Body Mass Index (BMI) = 38 kg/m2 (may be up to 40 kg/m2 after consultation with the Medical Monitor)
3. Females who are breastfeeding
4. Positive serum pregnancy test (female of childbearing potential)
5. Inability to exercise or exercise limitation due to other co-morbidities that may interfere with ability to perform required exercise SPECT MPI study (e.g., significant chronic lung disease, prior hospitalization for acute exacerbation of chronic lung disease or home oxygen use or chronic oral steroid therapy that can limit exercise capacity)
6. Any absolute contraindications to exercise stress testing
7. Any other conditions that, in the opinion of the investigator, are likely to prevent
compliance with the study protocol or pose a safety concern if the subject participates in the study
8. Participation in another trial of an investigational drug or device within 30 days (or
5 half-lives, whichever is greater) prior to Screening
Criteria Related to Medical History
9. Left bundle branch block
10. Automated implantable defibrillator
11. Pacemaker
12. Acute myocardial infarction within 60 days prior to Screening, or MI undergoing staged intervention during the duration of this study
13. Resting LV ejection fraction < 35%
14. Intervening coronary revascularization between the time of their prior clinically indicated exercise SPECT MPI study and Screening
15. Anticipated coronary revascularization during the study period
16. Unstable angina within 30 days prior to Screening
17. Coronary artery bypass graft (CABG) surgery within 60 days prior to Screening or
percutaneous coronary intervention (PCI) within 30 days prior to Screening
18. Cerebrovascular Attack (CVA) or Transient Ischemic Attack (TIA) within 90 days prior to Screening
19. History of serious arrhythmias
20. Currently in atrial fibrillation or atrial flutter
21. QTc interval > 500 milliseconds
22. Diagnosed as having New York Heart Association Class III or IV heart failure
23. Prior heart transplant
24. Clinically significant valvular or congenital heart disease
25. Severe pulmonary hypertension
26. Clinically significant hepatic impairment
27. Creatinine clearance < 30 mL/min according to the Cockcroft-Gault formula
Male: ((140 – age in years) × (wt in kg))/ (72 × (serum creatinine in mg/dL)) = CrCl (mL/min)
Female: ((140 – age in years) × (wt in kg))/(72 × (serum creatinine in mg/dL)) × 0.85 = CrCl (mL/min)
Criteria Related to Medications
28. Current or prior treatment with ranolazine
29. Class I or III antiarrhythmic medication
30. Current treatment with potent inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
31. Current treatment with CYP3A and P-gp inducers (e.g., rifampicin/rifampin, rifabutin, rifapentin, phenobarbital, carbamazepine, phenytoin and St. John’s wort)
32. Current treatment with CYP3A4 substrates with a narrow therapeutic range (e.g. cyclosporine, tacrolimus, sirolimus)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary efficacy endpoint of this study is to evaluate the effect of ranolazine (versus placebo) on exercise-induced PDS by automated polar maps.;Secondary Objective: Not applicable.;Primary end point(s): The primary efficacy endpoint of this study is to evaluate the effect of ranolazine (versus placebo) on exercise-induced PDS by automated polar maps.;Timepoint(s) of evaluation of this end point: Day 15 and 30.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary Endpoints:<br>1. Effect of ranolazine (versus placebo) on the following SPECT MPI variables:<br>a. Exercise-induced perfusion defect severity by automated polar maps.<br>b. Exercise-induced reversible perfusion defect size by automated polar maps;Timepoint(s) of evaluation of this end point: Day 15 and 30.