A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors
Overview
- Phase
- Phase 4
- Intervention
- Lorcaserin hydrochloride
- Conditions
- Cardiovascular Disease
- Sponsor
- Eisai Inc.
- Enrollment
- 14673
- Locations
- 478
- Primary Endpoint
- Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in overweight and obese subjects with cardiovascular (CV) disease and/or multiple CV risk factors.
Detailed Description
Approximately 12,000 subjects will be randomized to two treatment groups in a ratio of 1:1, stratified by the presence of established CV disease (approximately 80%) or CV risk factors without established CV disease (approximately 20%). Subjects will receive lorcaserin HCl 10 mg BID or placebo BID. The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization Phase will last up to 30 days and consist of one visit during which subjects will be screened for eligibility. The Randomization Phase will consist of two periods: Treatment and Follow-up. The Treatment Period will last for approximately 5 years with approximately 18 visits and Follow-up period is 30 (+ or - 10 days) from the end of treatment visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Lorcaserin hydrochloride (HCL)10 mg
APD356 10 mg twice daily
Intervention: Lorcaserin hydrochloride
Placebo
Placebo twice daily
Intervention: Placebo
Outcomes
Primary Outcomes
Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis
Time Frame: Baseline up to Month 42
The MACE events involved myocardial infarction (MI), stroke, or cardiovascular (CV) death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to First Occurrence of MACE+
Time Frame: Baseline up to end of study (Month 56)
The MACE+ events involved MI, stroke, or CV death or hospitalization for unstable angina or heart failure (HF), or any coronary revascularization. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Secondary Outcomes
- Time From Randomization to Conversion to Type 2 Diabetes Mellitus (T2DM) for Participants With Prediabetes at Baseline(Baseline up to end of study (Month 56))
- Time From Randomization to First Occurrence of the Individual Components of MACE+(Baseline up to end of study (Month 56))
- Time From Randomization to Event of All-cause Mortality(Baseline up to end of study (Month 56))
- Time From Randomization to Conversion to Normal Glucose Homeostasis in Participants With Prediabetes at Baseline(Baseline up to end of study (Month 56))
- Time From Randomization to Conversion to T2DM for Participants Without Any Type of Diabetes at Baseline(Baseline up to end of study (Month 56))
- Change From Baseline in HbA1c at Month 6 in Participants With T2DM at Baseline(Baseline, and Month 6)
- Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in All Participants(Baseline up to end of study (Month 56))
- Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Participants With T2DM at Baseline(Baseline up to end of study (Month 56))
- Percentage of Participants With FDA-Defined Valvulopathy at Baseline Who Demonstrated Worsened FDA-Defined Valvulopathy(Months 6 and 12)
- Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Participants With Prediabetes at Baseline(Baseline up to end of study (Month 56))
- Change From Baseline in Echocardiographically-Determined Pulmonary Arterial Systolic Pressure(Baseline, Month 12)
- Time From Randomization to Event of Improvement in Renal Function in Participants With T2DM at Baseline(Baseline up to end of study (Month 56))
- Percentage of Participants Who Met FDA-Defined Valvulopathy in Echocardiographically Determined Heart Valve Changes(Months 6 and 12)