A 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

Phase 4CompletedNCT02019264

Eisai Inc.14,673 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

14,673

Conditions

Cardiovascular Disease High Cardiovascular Risk Obesity

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria 1. BMI greater than or equal (\>=) to 27 kilogram per meter square (kg/m\^2) 2. Subjects able and willing to comply with a reduced-calorie diet and an increased physical activity program 3. Age \>= to 40 years with established CV disease as defined by one of the following: 1. History of documented MI or ischemic stroke 2. History of peripheral artery disease 3. History of revascularization (coronary, carotid, or peripheral artery) 4. Significant unrevascularized coronary arterial stenosis OR Age \>= to 55 years for women or \>= to 50 years for men who have type 2 diabetes mellitus (T2DM) without established CV disease plus at least one of the following CV risk factors: 1. Hypertension, or currently receiving therapy for documented hypertension 2. Dyslipidemia, or currently taking prescription lipid-lowering therapy for documented dyslipidemia 3. Estimated glomerular filtration rate \>= to 30 to less than equal (\<=) to 60 mililitre per minute per 1.73 meter square (mL/min/1.73 m\^) per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation 4. High high sensitivity C-reactive protein (hsCRP) 5. Urinary albumin-to-creatinine ratio (ACR) \>= 30 ug/mg Subjects with T2DM may have a pre-existing or new diagnosis of T2DM. A new diagnosis of T2DM (ie, discovered at Screening) should be based on the 2013 American Diabetes Association (ADA) guidelines. All T2DM subjects must have an HbA\[1c\] less (\<) than 10% at Screening. If subjects are being treated, or upon diagnosis need to be treated with antidiabetic agents, the T2DM treatment regimen must be stable for at least 3 months prior to randomization. Exclusion Criteria 1. Moderate or greater symptoms of congestive cardiac failure (New York Heart Association \[NYHA\] class III or IV) 2. Known left ventricular (LV) ejection fraction \< than 20% 3. Moderate or greater symptoms of pulmonary hypertension (PH) 4. Known severe valvular disease 5. Moderate renal impairment, severe renal impairment (estimated glomerular filtration rate \< 30 mL/min/1.73 m\^ per the CKD-EPI equation based on ideal body weight), or end stage renal disease (ESRD) 6. Severe hepatic impairment 7. Use of other products intended for weight loss including prescription drugs, over-the-counter (OTC) drugs, and herbal preparations 8. Use of more than one other serotonergic drug 9. Use of drugs known to increase the risk for cardiac valvulopathy within 6 months prior to Screening including, but not limited to: pergolide, ergotamine, methysergide, cabergoline 10. History or evidence of clinically significant disease (e.g., malignancy, cardiac, respiratory, gastrointestinal, renal or psychiatric disease) 11. Use of lorcaserin HCl prior to Screening or hypersensitivity to lorcaserin HCl or any of the excipients 12. Planned bariatric surgery 13. Females must not be breastfeeding or pregnant

Locations (499)

Advanced Cardiovascular, LLC

Alexander City, Alabama, United States

North Alabama Research Center, LLC

Athens, Alabama, United States

UAB Medical Center

Birmingham, Alabama, United States

Coastal Clinical Research, Inc.

Mobile, Alabama, United States

Mobile Heart Specialists, PC

Mobile, Alabama, United States

Outcomes

Primary Outcomes

Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis

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 frame: Baseline up to Month 42

Time From Randomization to First Occurrence of MACE+

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.