A Phase 3 Study of Ranolazine in Subjects With Type 2 Diabetes Who Are Not Well 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: January 17, 2014
Last verified: January 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 subjects with type 2 diabetes mellitus 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
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 Hemoglobin A1c [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in incremental change of 2-hour postprandial serum glucose [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The incremental change of 2-hour postprandial serum glucose (PPG) is defined as the difference between the 2-hour PPG and the fasting serum glucose (FSG).

  • Change from baseline in FSG or change from baseline in 2-hour PPG [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Enrollment: 442
Study Start Date: June 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine Drug: Ranolazine
Subjects will receive one tablet of ranolazine 500 mg twice daily followed by two tablets of ranolazine 500 mg twice daily, in addition to metformin, for the duration of the study.
Other Name: Ranexa
Placebo Comparator: Placebo Drug: Placebo
Subjects will receive one tablet of matching placebo twice daily followed by two tablets of matching placebo twice daily, in addition to metformin, for the duration of the study.

Detailed Description:

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 subjects with type 2 diabetes mellitus (T2DM) who are inadequately controlled despite current treatment with stable metformin therapy in addition to diet and exercise. The study has been designed to determine the effect of ranolazine on glycemic control and to characterize the relationship between HbA1c reduction and other glycemic parameters in subjects with T2DM.

  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 7% to 10%, inclusive, at Screening and at the end of Period 1
  • C-peptide ≥ 0.8 ng/mL at Screening
  • FSG ≥ 130 mg/dL (7.2 mmol/L) and ≤ 240 mg/dL (13.3 mmol/L) at Screening and at the end of Period 1

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
  • QTc interval > 500 msec by ECG at Screening, a personal or family history of QTc prolongation, congenital long QT syndrome, or subjects 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) > 3x upper limit of the normal range (ULN) and/or alanine aminotransferase (ALT) > 3x 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 the start of Period 2
  • 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 Period 2 Day 1
  • Treatment with CYP3A inducers or P-gp inducers within 14 days prior to Period 2 Day 1
  • Treatment with simvastatin or lovastatin at a dose > 20 mg or > 40 mg daily, respectively, within 14 days prior to Period 2 Day 1
  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
  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
Last Updated: January 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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Ranolazine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014