A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ranolazine; Placebo to match ranolazine; Metformin; Placebo to match metformin; Diet; Exercise
Intervention description: Ranolazine tablet(s) administered orally; Placebo to match ranolazine for the duration of the study; Metformin tablet(s) administered orally once daily; Placebo to match metformin for the duration of the study; Participants are instructed to continue the diet regimen prescribed by their physician.; Participants are instructed to continue the exercise regimen prescribed by their physician.
Intervention MeSH terms: Metformin; Ranolazine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 442.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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