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

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Placebo; Drug: Ranolazine

• Registration Number: NCT01163721
• Lead Sponsor: Gilead Sciences

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-15
• Study First Posted: 2010-07-16
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Disposition First Submitted: 2011-07-21
• Disposition First Submitted QC: 2011-07-21
• Disposition First Posted: 2011-07-25
• Status Verified: 2013-07
• Results First Submitted: 2013-07-19
• Results First Submitted QC: 2013-07-19
• Last Update Submitted: 2013-07-19
• Results First Posted: 2013-09-23
• Last Update Posted: 2013-09-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants were randomized to receive placebo to match ranolazine for 12 weeks.
Ranolazine	Ranolazine	Participants were randomized to receive ranolazine for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	Baseline to 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.
Change From Baseline in 2-hour Postprandial Serum Glucose at Week 12 Following a Standardized Meal	Baseline to Week 12	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.
Change From Baseline in Fasting Serum Glucose at Week 12	Baseline to 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.

Trial Locations

Locations (9)

National Research Institute (NRI); 🇺🇸 Los Angeles, California, United States

Vince and Associates Clinical Research; 🇺🇸 Overland Park, Kansas, United States

Cetero Research; 🇺🇸 San Antonio, Texas, United States

L-MARC Research Center; 🇺🇸 Louisville, Kentucky, United States

SeaView Research Inc.; 🇺🇸 Miami, Florida, United States

Rochester Clinical Research (RCR); 🇺🇸 Rochester, New York, United States

Orlando Clinical Research Center (OCRC); 🇺🇸 Orlando, Florida, United States

AMCR Institute; 🇺🇸 Escondido, California, United States

Midwest Institute For Clinical Research Inc. (MICR); 🇺🇸 Indianapolis, Indiana, United States