A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ranolazine When Added to Glimepiride in Subjects With Type 2 Diabetes Mellitus
Overview
- Phase
- Phase 3
- Intervention
- Ranolazine
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Gilead Sciences
- Enrollment
- 431
- Locations
- 139
- Primary Endpoint
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to determine the effect of ranolazine when added to glimepiride on glycemic control in adults with type 2 diabetes mellitus (T2DM) who are inadequately controlled despite current treatment with stable sulfonylurea or metformin therapy in addition to diet and exercise.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent
- •Males and females, 18 to 75 years old, inclusive
- •Documented history of T2DM
- •Receiving one of the following sulfonylurea or metformin therapies in addition to diet and exercise for at least 90 days prior to Screening:
- •glimepiride at a daily dose of ≥ 2 mg and ≤ 4 mg
- •glipizide, glyburide, or glibenclamide (or equivalent) at a daily dose of ≥ 7.5 mg
- •gliclazide at a daily dose of \> 160 mg (or ≥ 60 mg for the modified release \[MR\] formulation)
- •metformin at a daily dose of ≥ 1500 mg
- •Body mass index (BMI) 25 kg/m2 to 45 kg/m2, inclusive, at Screening
- •HbA1c 7% to 10%, inclusive, at Screening and the end of the Qualifying Period (Day 14)
Exclusion Criteria
- •History of or current diagnosis of type 1 diabetes mellitus
- •History of diabetic ketoacidosis, ketosis-prone diabetes, or hyperosmolar hyperglycemic coma
- •History of a severe episode of hypoglycemia (≥ 1 episode within 3 months prior to Screening or ≥ 2 episodes within 6 months prior to Screening), defined as hypoglycemia requiring 3rd party assistance to actively administer carbohydrate, glucagon, or other resuscitative actions due to severe impairment in consciousness or behavior
- •Clinically significant complications of diabetes that in the judgment of the investigator would make the subject unsuitable to participate in this study
- •History of any clinically significant cardiovascular (CV) or cerebrovascular event (eg, myocardial infarction \[MI\], acute coronary syndrome \[ACS\], recent revascularization \[including coronary artery bypass graft procedures or percutaneous coronary intervention\], transient ischemic attack, or ischemic stroke) ≤ 3 months prior to Screening
- •Inadequately controlled or unstable hypertension as defined by a systolic blood pressure (SBP) \> 160 mmHg or diastolic blood pressure (DBP) \> 100 mmHg at Screening and at Randomization
- •Prolonged QT interval corrected for heart rate (QTc) interval \> 500 msec by electrocardiogram (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)
- •History of bariatric surgery at any time in the past or or any other surgery \< 2 months before Screening; or planning to undergo surgery during the study. Subjects with a planned minor surgery may be enrolled upon approval by the medical monitor.
- •Any other hospitalization in the 14 days prior to Screening or planned hospitalization at any time during the study
- •Significant weight change (± 5%) \< 2 months prior to Screening or enrollment in a weight-loss program other than a maintenance phase at Screening.
Arms & Interventions
Ranolazine+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24. Participants will be required to maintain their diet and exercise regimen.
Intervention: Ranolazine
Ranolazine+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24. Participants will be required to maintain their diet and exercise regimen.
Intervention: Glimepiride
Ranolazine+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24. Participants will be required to maintain their diet and exercise regimen.
Intervention: Diet
Ranolazine+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive ranolazine 500 mg twice daily plus glimepiride 4 mg once daily on Days 1 through 7, followed by ranolazine 1000 mg twice daily plus glimepiride 4 mg once daily from Day 8 (or by Day 16 if not well tolerated) through Week 24. Participants will be required to maintain their diet and exercise regimen.
Intervention: Exercise
Placebo+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks. Participants will be required to maintain their diet and exercise regimen.
Intervention: Placebo
Placebo+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks. Participants will be required to maintain their diet and exercise regimen.
Intervention: Glimepiride
Placebo+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks. Participants will be required to maintain their diet and exercise regimen.
Intervention: Diet
Placebo+glimepiride
Glimepiride stabilization period (up to 8 weeks): participants not on stable glimepiride will receive glimepiride 2 mg once daily, and if tolerated the dose will be increased on Day 8 (+ 2 days) to 4 mg once daily. Qualifying period: participants will receive placebo to match ranolazine twice daily in addition to glimepiride for 14 days (+ 2 days) and if ≥ 80% compliant and meeting eligibility criteria will continue to the treatment period. Treatment period: participants will be randomized to receive placebo to match ranolazine plus glimepiride 4 mg once daily for 24 weeks. Participants will be required to maintain their diet and exercise regimen.
Intervention: Exercise
Outcomes
Primary Outcomes
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 Outcomes
- Change From Baseline in Incremental Change of 2-hour Postprandial Serum Glucose at Week 24(Baseline; Week 24)
- Change From Baseline in Fasting Serum Glucose at Week 24(Baseline; Week 24)
- Change From Baseline in 2-hour Postprandial Serum Glucose at Week 24(Baseline; Week 24)