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

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Behavioral: Exercise; Drug: Metformin; Drug: Placebo to match ranolazine; Drug: Placebo to match metformin; Drug: Ranolazine; Behavioral: Diet

Study type: Interventional

Funder types: Industry

Identifiers

NCT01555164

GS-US-259-0147

2012-001259-37 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 442 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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442 participants in 2 patient groups, including a placebo group

Ranolazine+metformin

Experimental group

Description:

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.

Treatment:

Behavioral: Diet

Drug: Ranolazine

Behavioral: Exercise

Drug: Metformin

Drug: Placebo to match metformin

Placebo+metformin

Placebo Comparator group

Description:

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.

Treatment:

Behavioral: Diet

Behavioral: Exercise

Drug: Metformin

Drug: Placebo to match ranolazine