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

Inclusion Criteria:

1. ≥50 years of age (women) or ≥45 years of age (men)

2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2

3. Waist circumference ≥88 cm (women) or ≥102 cm (men)

4. 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:

1. Myocardial infarction within 3 months prior to screening

2. Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading
scheme

3. Clinical history of cerebrovascular disease (stroke)

4. History of tachyarrhythmia other than sinus tachycardia

5. Planned bariatric surgery, cardiac surgery, or coronary angioplasty

6. History of seizures (including febrile seizures), cranial trauma, or other conditions
that predispose the subject to seizures

7. History of mania or current diagnosis of active psychosis, active bulimia or anorexia
nervosa (binge eating disorder is not exclusionary)

8. Any condition with life expectancy anticipated to be less than 4 years (e.g.,
congestive heart failure NYHA Class 3 or 4)