Exploratory Study to Access the Metabolic Effects of Ranolazine in Subjects With Type 2 Diabetes Mellitus When Added to Ongoing Non-insulin Antidiabetic Therapy

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group Exploratory Study to Access the Metabolic Effects of Ranolazine When Added to Ongoing Non-Insulin Antidiabetic Therapy in Subjects With Type 2 Diabetes Mellitus

This study enrolled participants with inadequately controlled type 2 diabetes mellitus (T2DM) despite non-insulin antidiabetic therapy in addition to diet and exercise, and would have benefited from additional control of blood glucose levels. The study assessed the metabolic effects of ranolazine, including its effect in lowering glycosylated hemoglobin A1c (HbA1c), and lowering glucose while fasting, and following a meal (postprandial).

Participants were randomized in a 1:1 ratio to receive ranolazine or placebo, and were stratified by HbA1c ≤ 7.5% or > 7.5%. Enrollment was to include no more than two-thirds of participants with baseline HbA1c ≤ 7.5%. Other than glucose values, efficacy endpoint results remained blinded during the study; for safety purposes, the investigator was to be alerted of severe hyperglycemia or hypoglycemia.

Participants were instructed to maintain logs of their physical activity/exercise (Subject Activity Assessment) and study drug dosing (Dosing Log).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Ranolazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Escondido, California, United States, 92026
      • AMCR Institute
    • Los Angeles, California, United States, 90057
      • National Research Institute (NRI)
  • Florida
    • Miami, Florida, United States, 33126
      • SeaView Research Inc.
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center (OCRC)
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute For Clinical Research Inc. (MICR)
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research (RCR)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cetero Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant with T2DM on stable non-insulin antidiabetic therapy in addition to diet and exercise
• Body mass index (BMI) ≥ 25 kg/m^2 and ≤ 40 kg/m^2
• HbA1c 7 - 11%
• Ability and willingness to maintain a complete and accurate Subject Activity Log during the course of the trial
• Female of child-bearing potential must have agreed to use effective methods of contraception
• Ability to understand and willing to sign written informed consent

Exclusion Criteria:

• Type 1 Diabetes Mellitus (T1DM)
• T2DM with history of or current insulin therapy. Prior use during pregnancy or gestational diabetes was acceptable.
• History of ketoacidosis or ketosis-prone diabetes
• Clinically significant complications of diabetes that in the judgment of the investigator would have made participant unsuitable to participate in this trial
• History of a severe episode of hypoglycemia
• Change in non-insulin antidiabetic therapy in addition to diet and exercise < 2 months prior to screening
• Any clinically significant cardiovascular event < 2 months prior to screening
• Clinically significant, inadequately controlled or unstable hypertension
• Hospitalization < 2 months prior to screening
• Major surgery < 3 months prior to screening
• Weight loss medication (prescription or non-prescription) < 2 months prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranolazine; Participants were randomized to receive ranolazine for 12 weeks.	Drug: Ranolazine; Ranolazine ER 1000 mg (two 500 mg tablets) administered orally twice daily; Other Names: Ranexa®
Placebo Comparator: Placebo; Participants were randomized to receive placebo to match ranolazine for 12 weeks.	Drug: Placebo; Placebo to match ranolazine administered orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	HbA1c is a blood test to measure blood sugar control over the prior 3-month period. The last observation carried forward (LOCF) method was used: the last observed post-baseline measurements prior to Week 12 carried forward for participants with no available Week 12 values. Participants were summarized according to the actual treatment received regardless of the allocated treatment.	Baseline to Week 12
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 12 Following a Standardized Meal	2-hour postprandial serum glucose was defined as the average of serum glucose measurement at 120 minutes and 125 minutes following a standardized meal. The LOCF method was used. Participants were summarized according to the actual treatment received regardless of the allocated treatment.	Baseline to Week 12
Change From Baseline in Fasting Serum Glucose at Week 12	Serum glucose was measured following an overnight fast. The LOCF method was used. Participants were summarized according to the actual treatment received regardless of the allocated treatment.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: July 14, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Estimate): September 23, 2013
• Last Update Submitted That Met QC Criteria: July 19, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: HbA1c; Type 2 diabetes mellitus; T2DM; Ranolazine; Ranexa
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: GS-US-259-0107