Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors (The Light Study)

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of NB relative to placebo on major adverse cardiovascular events (MACE) such as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in overweight and obese subjects who are at a higher risk of having these events because they have diabetes and/or other cardiovascular risk factors.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Occurrence of Major Adverse Cardiovascular Events (MACE) in Overweight and Obese Subjects With Cardiovascular Risk Factors Receiving Naltrexone SR/Bupropion SR

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: NB32
* Drug: PBO
* Behavioral: Weight Management Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥50 years of age (women) or ≥45 years of age (men) Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2 Waist circumference ≥88 cm (women) or ≥102 cm (men) At increased risk of adverse cardiovascular outcomes: Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following: History of documented myocardial infarction >3 months prior to screening History of coronary revascularization History of carotid or peripheral revascularization Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study Ankle brachial index <0.9 (by simple palpation) within prior 2 years ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years AND/OR Type 2 diabetes mellitus with at least 2 of the following: Hypertension (controlled with or without pharmacotherapy at <145/95 mm Hg) Dyslipidemia requiring pharmacotherapy Documented low HDL cholesterol (<50 mg/dL in women or <40 mg/dL in men) within prior 12 months Current tobacco smoker Exclusion Criteria: Myocardial infarction within 3 months prior to screening Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading scheme Clinical history of cerebrovascular disease (stroke) History of tachyarrhythmia other than sinus tachycardia Planned bariatric surgery, cardiac surgery, or coronary angioplasty History of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the subject to seizures History of mania or current diagnosis of active psychosis, active bulimia or anorexia nervosa (binge eating disorder is not exclusionary) Any condition with life expectancy anticipated to be less than 4 years (e.g., congestive heart failure NYHA Class 3 or 4)

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NB32<br> | Drug: NB32<br>* Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.<br>* Other names: CONTRAVE;Behavioral: Weight Management Program<br>* A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.<br>* Other names: WeightMate (Tm);|
| Placebo Comparator: PBO<br> | Drug: PBO<br>* Placebo. Administered in addition to the weight management program.<br>Behavioral: Weight Management Program<br>* A comprehensive weight management program will be administered in addition to the subject's study medication assignment. The program includes internet counseling by an accredited health and fitness professional and a nutrition and exercise program with goal setting and educational and tracking tools.<br>* Other names: WeightMate (Tm);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Confirmed Occurrence of Major Adverse Cardiovascular Event (MACE) | The primary endpoint is the time from randomization to the first confirmed occurrence of any event within the primary MACE composite (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). Due to early termination of the study, pre-planned 50% interim analysis is considered the primary analysis for outcome measures. The pre-planned 50% interim analysis was conducted when 50% of the total planned MACE were observed. | Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death, Nonfatal Myocardial Infarction, Nonfatal Stroke, or Nonfatal Unstable Angina Requiring Hospitalization | Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures. | Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up | 
| Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death (Including Fatal Myocardial Infarction, Fatal Stroke) | Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures. | Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up | 
| Percentage of Participants With a Confirmed Occurrence of Myocardial Infarction (Nonfatal or Fatal) | Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures. | Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up | 
| Percentage of Participants With a Confirmed Occurrence of Stroke (Nonfatal or Fatal) | Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures. | Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body Weight, Bupropion, Cardiovascular Diseases, Diabetes Mellitus, Diabetes Mellitus, Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Heart Diseases, Metabolic Diseases, Narcotic Antagonists, Naltrexone, Nutrition Disorders, Obesity, Overnutrition, Overweight