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

Phase 3

Terminated

• Conditions: Obesity; Overweight
• Interventions: Drug: NB32; Drug: PBO; Behavioral: Weight Management Program

• Registration Number: NCT01601704
• Lead Sponsor: Orexigen Therapeutics, Inc

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-14
• Study First Submitted QC: 2012-05-16
• Study First Posted: 2012-05-18
• Study Start: 2012-06
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2016-04
• Results First Submitted: 2016-12-11
• Results First Submitted QC: 2017-02-24
• Last Update Submitted: 2017-02-24
• Results First Posted: 2017-02-27
• Last Update Posted: 2017-02-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8910

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NB32	NB32	-
NB32	Weight Management Program	-
PBO	PBO	-
PBO	Weight Management Program	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Confirmed Occurrence of Major Adverse Cardiovascular Event (MACE)	Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up	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.

Secondary Outcome Measures

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