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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01555164
First received: March 13, 2012
Last updated: September 17, 2014
Last verified: September 2014

March 13, 2012
September 17, 2014
June 2012
September 2013   (final data collection date for primary outcome measure)
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.
HbA1c [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01555164 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 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.

  • Postprandial serum glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Fasting serum glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Inadequately Controlled on Metformin Alone
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Ranolazine When Added to Metformin in Subjects With Type 2 Diabetes Mellitus

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Ranolazine
    Ranolazine tablet(s) administered orally
    Other Name: Ranexa®
  • Drug: Placebo to match ranolazine
    Placebo to match ranolazine for the duration of the study
  • Drug: Metformin
    Metformin tablet(s) administered orally once daily
  • Drug: Placebo to match metformin
    Placebo to match metformin for the duration of the study
  • 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+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.

    Interventions:
    • Drug: Ranolazine
    • Drug: Metformin
    • Drug: Placebo to match metformin
    • Behavioral: Diet
    • Behavioral: Exercise
  • Placebo Comparator: Placebo+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.

    Interventions:
    • Drug: Placebo to match ranolazine
    • Drug: Metformin
    • Behavioral: Diet
    • Behavioral: Exercise
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
442
October 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Ukraine,   Russian Federation,   South Africa,   India,   Hungary,   Poland,   Canada,   Israel,   Mexico,   Czech Republic
 
NCT01555164
GS-US-259-0147, 2012-001259-37
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Patrick Yue, MD Gilead Sciences
Gilead Sciences
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP