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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Gilead Sciences
- Enrollment
- 465
- Locations
- 157
- Primary Endpoint
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Investigators
Eligibility 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
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
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: Diet
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.
Intervention: Exercise
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.
Intervention: Ranolazine
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.
Intervention: Placebo
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.
Intervention: Diet
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.
Intervention: Exercise
Outcomes
Primary Outcomes
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Time Frame: Baseline; Week 24
The average (mean) change from baseline in HbA1c at Week 24 was analyzed.
Secondary Outcomes
- Change From Baseline in Fasting Serum Glucose at Week 24(Baseline; Week 24)
- Percentage of Participants With HbA1c < 7% at Week 24(Week 24)
- Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24(Baseline; Week 24)
- Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24(Baseline; Week 24)