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
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Enrollment: 442
Study Start Date: June 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555164

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

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01555164     History of Changes
Other Study ID Numbers: GS-US-259-0147, 2012-001259-37
Study First Received: March 13, 2012
Results First Received: September 17, 2014
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
India: Drugs Controller General of India
Israel: Ministry of Health
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Ranolazine
Enzyme Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014