A Study on the Effects of Ranolazine on Exercise Duration in Subjects With Chronic Stable Angina and Coronary Artery Disease (CAD) With Type 2 Diabetes Mellitus (T2DM)

Coronary Artery Disease Clinical Trial

Official title:

A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel Study of Ranolazine in Subjects With Chronic Stable Angina and Coronary Artery Disease With a History of Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01334203
• Other study ID #: GS-US-259-0108
• Status: Withdrawn
• Phase: Phase 4
• First received: April 11, 2011
• Last updated: July 27, 2012
• Start date: May 2011
• Est. completion date: December 2012

Study information

• Verified date: July 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaCanada: Ethics Review CommitteeBelarus: Ministry of HealthCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: National Consultative Ethics Committee for Health and Life SciencesGeorgia: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesIsrael: Ethics CommissionIsrael: Ministry of HealthPoland: Ethics CommitteePoland: The Central Register of Clinical TrialsRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSerbia: Ethics CommitteeSingapore: Domain Specific Review BoardsSingapore: Health Sciences AuthoritySweden: Medical Products AgencySweden: Regional Ethical Review BoardUkraine: Ethics CommitteeUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy of ranolazine compared to placebo on duration of exercise assessed by exercise tolerance testing (ETT) at anticipated peak ranolazine plasma concentration after 12 weeks of treatment in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM).

Description:

This study will evaluate the efficacy of ranolazine compared to placebo on duration of exercise assessed by exercise tolerance testing (ETT) at anticipated peak ranolazine plasma concentration after 12 weeks of treatment in subjects with chronic stable angina and coronary artery disease (CAD) who have a history of type 2 diabetes mellitus (T2DM). This is a randomized, double-blind, placebo-controlled, parallel group study in subjects with chronic stable angina and CAD receiving a stable dose of a single concomitant antianginal medication who also have a history of T2DM; allowed antianginals will be a beta-blocker (atenolol or metoprolol) or a calcium-channel blocker.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Written informed consent

• Males and females aged 18 to 79 years

• Able to perform a Sheffield Modified Bruce Treadmill Exercise Protocol

• At least a 3-months history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin

• Coronary artery disease documented by one or more of the following:

• Angiographic evidence of = 50% stenosis of one or more major coronary arteries

• History of myocardial infarction (MI) documented by positive CK-MB enzymes, troponins, or ECG changes

• Cardiac nuclear scan studies diagnostic of CAD, e.g., thallium scan or ECHO with stress or pharmacologic interventions (adenosine, dipyridamole, etc.)

• Stable treatment with one of the following antianginal medications for at least 4 weeks prior to Screening:

• beta-blocker (atenolol up to 50 mg daily or metoprolol up to 100 mg daily)

• dihydropyridine calcium-channel blocker (amlodipine up to 5 mg daily or nifedipine up to 30 mg daily)

• non-dihydropyridine calcium-channel blocker (diltiazem 180 to 360 mg daily or verapamil 180 to 360 mg daily)

• Willingness to discontinue other antianginals and be treated with one of the allowed antianginal therapies

• Documented history of type 2 diabetes mellitus

• 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.

Exclusion Criteria:

• Inability to exercise or having exercise limitation due to other co-morbidities that may interfere with ability to perform required ETT (e.g., morbid obesity, significant chronic lung disease, prior hospitalization for acute exacerbation of chronic lung disease or home oxygen use, chronic oral steroid therapy that can limit exercise capacity, osteoarthritis, peripheral artery disease, etc.)

• Any absolute contraindication to ETT

• Presence of electrocardiographic or other abnormalities that interfere with ECG interpretation or may cause a false positive stress test (e.g., = 1 mm horizontal or down-sloping ST segment depression at rest in any standard ECG lead, Lown-Ganong-Levine syndrome, Wolff-Parkinson-White syndrome, left bundle branch block, left ventricular hypertrophy with repolarization abnormality, ventricular pacemaker, etc.)

• Decompensated heart failure

• Clinically significant valvular heart disease or congenital cardiac defects

• Acute coronary syndrome in the prior 2 months or coronary revascularization within the prior 6 months or planned coronary revascularization during the study period

• Stroke or transient ischemic attack within 6 months prior to Screening

• History of serious ventricular dysrhythmias or a history of life-threatening ventricular arrhythmia

• Atrial fibrillation

• QTc > 0.5 seconds

• Hypertrophic cardiomyopathy

• Uncontrolled hypertension (seated systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)

• Systolic blood pressure < 90 mm Hg

• Inability to discontinue current antianginal medications and remain on one allowed antianginal therapy

• Clinically significant hepatic impairment

• Creatinine clearance (CLCr) < 30 ml/min

• Prior treatment with ranolazine

• Participation in another investigational drug or device study within 1 month prior to Screening

• Females who are breastfeeding

• Positive serum pregnancy test

• Current treatment with potent inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)

• Current treatment with CYP3A and P glycoprotein (Pgp) inducers (e.g., rifampicin/rifampin, carbamazepine, St. John's wort)

• History of illicit drug use or alcohol abuse within one year of screening

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ranolazine
Subjects will be randomized to either ranolazine 500 mg twice daily up-titrated on Day 4 to 1000 mg administered orally twice a day or matching placebo for the 12 week treatment period. Subjects receiving diltiazem or verapamil as their concomitant antianginal medication will receive ranolazine 500 mg or placebo administered orally twice a day.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy endpoint is the change from baseline in exercise treadmill duration in the peak ETT at week 12 or last visit.		12 weeks	No
Secondary	Time to onset of angina during peak ETT at week 12 or last visit		12 weeks	No
Secondary	Time to onset of 1 mm ST-segment depression during peak ETT at week 12 or last visit		12 weeks	No
Secondary	Change from baseline in exercise treadmill duration in the trough ETT at week 12		12 weeks	No