Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01472185
First received: November 11, 2011
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to determine the effect of ranolazine when given as monotherapy on glycemic control in subjects with type 2 diabetes mellitus (T2DM) who were inadequately controlled with diet and exercise alone and who are treatment naive to antihyperglycemic therapy or have not received antihyperglycemic therapy in the 90 days (or thiazolidinediones [TZDs] for at least 24 weeks) prior to screening, and to characterize the relationship between HbA1c reduction and other glycemic parameters in subjects with T2DM.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ranolazine
Drug: Placebo
Behavioral: Diet
Behavioral: Exercise
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ranolazine Monotherapy in Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    The average (mean) change from baseline in HbA1c at Week 24 was analyzed.


Secondary Outcome Measures:
  • Change From Baseline in Fasting Serum Glucose at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.

  • Percentage of Participants With HbA1c < 7% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]

    The average (mean) change from baseline in 2-hour postprandial serum glucose at Week 24 was analyzed.

    Mixed Meal Tolerance Test (MMTT) Full Analysis Set: randomized participants who received at least one dose of study treatment with a baseline and at least one postbaseline measurement of serum glucose at time [T] = 120 minutes during the MMTT, administered under fasting conditions, excluding participants with major eligibility protocol violations and analyzed based on the randomized treatment regardless of actual treatment received.


  • Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    The average (mean) change from baseline in incremental change of 2-hour postprandial serum glucose at Week 24 was analyzed.


Enrollment: 465
Study Start Date: November 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Qualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days.

Treatment Period: Placebo to match ranolazine (Days 1-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Drug: Placebo
Placebo to match ranolazine administered orally twice daily.
Behavioral: Diet
Participants are instructed to continue the diet regimen prescribed by their physician.
Behavioral: Exercise
Participants are instructed to continue the exercise regimen prescribed by their physician.
Experimental: Ranolazine

Qualifying Period: Placebo to match ranolazine (1 tablet twice daily) for 14 days.

Treatment Period: Ranolazine tablets (Days 1-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 24 weeks.

Participants were required to maintain their diet and exercise regimen.

Drug: Ranolazine
Ranolazine tablets administered orally twice daily.
Other Name: Ranexa®
Drug: Placebo
Placebo to match ranolazine administered orally twice daily.
Behavioral: Diet
Participants are instructed to continue the diet regimen prescribed by their physician.
Behavioral: Exercise
Participants are instructed to continue the exercise regimen prescribed by their physician.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Males and females, 18 to 75 years old, inclusive
  • Documented history of T2DM
  • Treatment naïve to antihyperglycemic therapy or having received no prior treatment with antihyperglycemic therapy for at least 90 days (TZDs for at least 24 weeks) prior to screening
  • Body mass index (BMI) 25 kg/m2 to 45 kg/m2 inclusive at screening
  • HbA1c 7% - 10%, inclusive at screening and at the end of the Qualifying Period (Day 14 +2 days)
  • Fasting serum glucose (FSG) of ≥ 130 mg/dL (7.2 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at screening and at the end of the Qualifying Period (Day 14 +2 days). A one-time central laboratory re-test of FSG is allowed in subjects with an initial central laboratory FSG ≥ 125 mg/dL (6.9 mmol/L) and < 130 mg/dL (7.2 mmol/L) who are otherwise eligible as determined by the investigator.
  • Fasting serum C-peptide ≥ 0.8 ng/mL at screening
  • Able and willing to comply with all study procedures during the course of the study
  • Females of child-bearing potential must have a negative pregnancy test at screening and must agree to use highly effective contraception methods from screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug
  • At least 80% compliant with dosing during the Qualifying Period

Exclusion Criteria:

  • History of or current diagnosis of type 1 diabetes mellitus
  • History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
  • History of a severe episode of hypoglycemia (≥ 1 episode within 3 months prior to screening or ≥ 2 episodes within 6 months prior to screening), defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate, glucagon, or other resuscitative actions due to severe impairment in consciousness or behavior
  • Clinically significant complications of diabetes that, in the judgment of the investigator, would make the subject unsuitable to participate in this study
  • History of any clinically significant cardiovascular or cerebrovascular event (eg, myocardial infarction [MI], acute coronary syndrome [ACS], recent coronary revascularization [including coronary artery bypass graft procedures or percutaneous coronary intervention], transient ischemic attack or ischemic stroke) ≤ 3 months prior to screening
  • Inadequately controlled or unstable hypertension as defined by systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at screening and randomization
  • Prolonged QTc interval > 500 msec by ECG at screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
  • History of bariatric surgery at any time in the past or any other surgery < 2 months before screening, or planning to undergo surgery during the study. Subjects with a planned minor surgery may be enrolled upon approval by the Medical Monitor.
  • Any other hospitalization in the 14 days prior to screening or planned hospitalization at any time during the study
  • Significant weight change (± 5%) < 2 months prior to screening or on a weight-loss program and is not in the maintenance phase at screening
  • Severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation < 30 mL/min/1.73 m2 at screening or undergoing any type of dialysis at screening or planning to undergo any type of dialysis during the course of the study.
  • History of liver cirrhosis (Child-Pugh Class A, B or C)
  • Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x ULN and/or serum total bilirubin > 2.0 mg/dL
  • History of cancer (except non-melanomic skin cancers or cervical in situ) within 5 years prior to screening
  • History of alcohol or other drug abuse < 12 months prior to screening
  • Any other clinically significant existing medical or psychiatric condition, including clinically significant laboratory abnormalities, or one requiring further evaluation that, in the opinion of the investigator, could interfere with conduct of the study or interpretation of the data
  • Prior treatment with open-label ranolazine or known hypersensitivity or intolerance to ranolazine or any of its excipients
  • Treatment with strong or moderate cytochrome (CYP)3A inhibitors or P-glycoprotein (P-gp) inhibitors within 14 days prior to randomization
  • Treatment with CYP3A inducers or P-gp inducers within 14 days prior to randomization
  • Treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, sirolimus) within 14 days prior to randomization
  • Treatment with simvastatin at a daily dose > 20 mg or lovastatin at a daily dose > 40 mg, within 14 days prior to randomization
  • Weight-loss medication or anti-obesity medication (prescription or nonprescription) < 3 months prior to screening
  • Treatment with niacin > 200 mg daily; if receiving ≤ 200 mg daily, should be on stable doses for ≥ 90 days prior to screening and for the duration of the study
  • Expected or current treatment with systemic corticosteroids (oral or injectable) for > 14 days from screening through the end of the Treatment Period. Topical or inhaled corticosteroid formulations are permitted at any time during the study
  • If receiving thyroid replacement therapy, should be on stable doses for at least 6 weeks prior to randomization
  • Hemoglobin < 12 g/dL for males; or < 11 g/dL for females, at screening
  • Participation in another clinical study involving an investigational drug or device < 30 days prior to screening; participation in another clinical study involving an antihyperglycemic therapy < 90 days prior to screening
  • Donation of blood < 2 months prior to screening; plans to donate blood while participating in the study
  • Females who are pregnant or breastfeeding
  • Other condition(s) that, in the opinion of the investigator, would compromise the safety of the subject, would prevent compliance with the study protocol (including the ability to comply with Mixed Meal Tolerance Test [MMTT]), or would compromise the quality of the clinical study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472185

  Show 159 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01472185     History of Changes
Other Study ID Numbers: GS-US-259-0131
Study First Received: November 11, 2011
Results First Received: October 8, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Hungary: Institutional Ethics Committee
Hungary: National Institute of Pharmacy
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: Ethics Committee
Romania: National Medicines Agency
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Serbia: Ethics Committee
Slovakia: State Institute for Drug Control
Slovakia: Ethics Committee
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
Ukraine: Ethics Committee
Ukraine: Ministry of Health

Keywords provided by Gilead Sciences:
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014