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

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ClinicalTrials.gov Identifier: NCT01555164
Recruitment Status : Completed
First Posted : March 15, 2012
Results First Posted : September 23, 2014
Last Update Posted : September 23, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Ranolazine Drug: Placebo to match ranolazine Drug: Metformin Drug: Placebo to match metformin Behavioral: Diet Behavioral: Exercise Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 442 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2012
Primary Completion Date : September 2013
Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.

Drug: Ranolazine
Ranolazine tablet(s) administered orally
Other Name: Ranexa®
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.
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.

Drug: Placebo to match ranolazine
Placebo to match ranolazine for the duration of the study
Drug: Metformin
Metformin tablet(s) administered orally once daily
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.


Outcome Measures

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Change From Baseline in Fasting Serum Glucose at Week 24 [ Time Frame: Baseline; Week 24 ]
    The average (mean) change from baseline in fasting serum glucose at Week 24 was analyzed.

  2. Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24 [ Time Frame: 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.



Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01555164


  Show 146 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Patrick Yue, MD Gilead Sciences
More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01555164     History of Changes
Other Study ID Numbers: GS-US-259-0147
2012-001259-37 ( EudraCT Number )
First Posted: March 15, 2012    Key Record Dates
Results First Posted: September 23, 2014
Last Update Posted: September 23, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Ranolazine
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action