A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Ranolazine; Drug: Placebo to match ranolazine; Drug: Metformin; Drug: Placebo to match metformin; Behavioral: Diet; Behavioral: Exercise

• Registration Number: NCT01555164
• Lead Sponsor: Gilead Sciences

Brief Summary

This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to determine the effect of ranolazine when added to metformin on glycemic control in adults with type 2 diabetes mellitus (T2DM) who are inadequately controlled despite current treatment with stable metformin therapy in addition to diet and exercise.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-03-13
• Study First Submitted QC: 2012-03-13
• Study First Posted: 2012-03-15
• Study Start: 2012-06
• Primary Completion: 2013-09
• Study Completion: 2013-10
• Disposition First Submitted: 2014-01-17
• Disposition First Submitted QC: 2014-01-17
• Disposition First Posted: 2014-02-13
• Status Verified: 2014-09
• Results First Submitted: 2014-09-17
• Results First Submitted QC: 2014-09-17
• Last Update Submitted: 2014-09-17
• Results First Posted: 2014-09-23
• Last Update Posted: 2014-09-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 442

Inclusion Criteria

• Documented history of T2DM
• Metformin therapy at a stable total daily dose ≥ 1500 mg and ≤ 2550 mg in addition to diet and exercise for ≥ 8 weeks prior to Screening
• Body mass index (BMI) 25 to 45 kg/m^2, inclusive, at Screening
• HbA1c within specified ranges at Screening and at the end of the Qualifying Period based on current metformin dose
• C-peptide ≥ 0.8 ng/mL at Screening
• Fasting serum glucose (FSG) ≥ 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

Exclusion Criteria

• Type 1 diabetes mellitus
• History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
• History of severe hypoglycemia
• Any clinically significant cardiovascular or cerebrovascular event ≤ 3 months prior to Screening
• History of congestive heart failure
• Corrected QT interval (QTc) > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or individuals who are receiving drugs that prolong the QTc interval, such as Class Ia or Class III antiarrhythmic agents, erythromycin, and certain antipsychotics (eg, ziprasidone)
• Serum creatinine concentration ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females at Screening
• Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase (AST) > 3 x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3 x ULN and/or serum total bilirubin > 2.0 mg/dL
• Use of any non-insulin antihyperglycemic therapy (other than metformin) for more than 14 days (consecutive or not) during the 12 weeks (24 weeks for thiazolidinediones) prior to Screening and/or use of any antihyperglycemic therapy other than metformin, at any dose, at any time during the 4 weeks prior to randomization
• Treatment with chronic insulin within 24 weeks prior to Screening (except for one temporary period of daily insulin injections no longer than 7 days)
• Treatment with strong or moderate cytochrome P450 3A (CYP3A) 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 simvastatin or lovastatin at a dose > 20 mg or > 40 mg daily, respectively, within 14 days prior to randomization

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ranolazine+metformin	Ranolazine	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen.
Ranolazine+metformin	Placebo to match metformin	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen.
Ranolazine+metformin	Diet	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen.
Ranolazine+metformin	Exercise	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen.
Placebo+metformin	Placebo to match ranolazine	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24. Participants are required to maintain their diet and exercise regimen.
Placebo+metformin	Metformin	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24. Participants are required to maintain their diet and exercise regimen.
Placebo+metformin	Diet	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24. Participants are required to maintain their diet and exercise regimen.
Placebo+metformin	Exercise	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily through Week 24. Participants are required to maintain their diet and exercise regimen.
Ranolazine+metformin	Metformin	Qualifying Period: Participants will receive metformin 1000 mg + placebo to match ranolazine twice daily for either 2 or 8 weeks (dependent on metformin dose and HbA1c level at Screening). Treatment Period: Participants will receive ranolazine 500 mg + metformin 500 mg + placebo to match metformin twice daily on Days 1 through 7, followed by ranolazine 1000 mg + metformin 500 mg + placebo to match metformin twice daily from Day 8 through Week 24. Participants are required to maintain their diet and exercise regimen.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	Baseline; Week 24	The average (mean) change from baseline in HbA1c at Week 24 was analyzed.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Serum Glucose at Week 24	Baseline; Week 24	The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24	Baseline; Week 24	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 T=120 minutes during the MMTT, administered under fasting conditions, excluding participants with major eligibility protocol violations; analyzed based on the randomized treatment regardless of actual treatment received.

Trial Locations

Locations (142)

Fundamental Research LLC; 🇺🇸 Gulf Shores, Alabama, United States

KLR Business Group DBA Arkansas Clinical Research; 🇺🇸 Little Rock, Alaska, United States

Radiant Research, Inc.; 🇺🇸 Chandler, Arizona, United States

Central Phoenix Medical Clinic; 🇺🇸 Phoenix, Arizona, United States

Clinical Research Advantage; 🇺🇸 Henderson, Nevada, United States

Desert Sun Clinical Research, LLC; 🇺🇸 Tucson, Arizona, United States

National Research Institute; 🇺🇸 Los Angeles, California, United States

Ritchken and First MD's; 🇺🇸 San Diego, California, United States

Clearview Medical Research, LLC; 🇺🇸 Santa Clarita, California, United States

Metabolic Institute of America; 🇺🇸 Tarzana, California, United States

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