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

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

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.

Study Overview

• Status: Terminated
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: NB32; Behavioral: Weight Management Program; Drug: PBO

• Study Type: Interventional
• Enrollment (Actual): 8910
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Dothan, Alabama, United States
    • Mobile, Alabama, United States
    • Scottsboro, Alabama, United States
  • Arizona
    • Chandler, Arizona, United States
    • Mesa, Arizona, United States
    • Peoria, Arizona, United States
    • Phoenix, Arizona, United States
    • Scottsdale, Arizona, United States
    • Tucson, Arizona, United States
    • Tuscson, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Anaheim, California, United States
    • Carmichael, California, United States
    • Escondido, California, United States
    • Fresno, California, United States
    • Harbor City, California, United States
    • Huntington Beach, California, United States
    • La Jolla, California, United States
    • Lomita, California, United States
    • Los Angeles, California, United States
    • Paramount, California, United States
    • Pasadena, California, United States
    • Riverside, California, United States
    • Sacramento, California, United States
    • Santa Rosa, California, United States
    • Spring Valley, California, United States
    • Thousand Oaks, California, United States
    • Torrance, California, United States
    • West Hills, California, United States
  • Colorado
    • Colorado Springs, Colorado, United States
    • Denver, Colorado, United States
    • Golden, Colorado, United States
    • Wheat Ridge, Colorado, United States
  • Connecticut
    • Norwalk, Connecticut, United States
    • Stamford, Connecticut, United States
  • Delaware
    • Wilmington, Delaware, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Boynton Beach, Florida, United States
    • Brooksville, Florida, United States
    • Clearwater, Florida, United States
    • Deland, Florida, United States
    • Delray Beach, Florida, United States
    • Gainesville, Florida, United States
    • Jacksonville, Florida, United States
    • Jacksonville Beach, Florida, United States
    • Melbourne, Florida, United States
    • Miami, Florida, United States
    • New Port Richey, Florida, United States
    • New Smyrna Beach, Florida, United States
    • Oakland Park, Florida, United States
    • Orlando, Florida, United States
    • Palm Harbor, Florida, United States
    • Pembroke Pines, Florida, United States
    • Pensacola, Florida, United States
    • Pinellas Park, Florida, United States
    • Saint Petersburg, Florida, United States
    • Vero beach, Florida, United States
    • Wellington, Florida, United States
    • Winter Haven, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Austell, Georgia, United States
    • Columbus, Georgia, United States
    • Lawrenceville, Georgia, United States
    • Riverdale, Georgia, United States
    • Savannah, Georgia, United States
    • Stockbridge, Georgia, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Idaho
    • Meridian, Idaho, United States
  • Illinois
    • Chicago, Illinois, United States
    • Gurnee, Illinois, United States
    • Melrose Park, Illinois, United States
  • Indiana
    • Bloomington, Indiana, United States
    • Brownsburg, Indiana, United States
    • Elwood, Indiana, United States
    • Evansville, Indiana, United States
    • Hammond, Indiana, United States
    • South Bend, Indiana, United States
    • Valparaiso, Indiana, United States
  • Iowa
    • Ames, Iowa, United States
    • Council Bluffs, Iowa, United States
    • Des Moines, Iowa, United States
    • West Des Moines, Iowa, United States
  • Kansas
    • Overland Park, Kansas, United States
    • Wichita, Kansas, United States
  • Kentucky
    • Crestview Hills, Kentucky, United States
    • Louisville, Kentucky, United States
    • Mount Sterling, Kentucky, United States
  • Louisiana
    • Alexandria, Louisiana, United States
    • Baton Rouge, Louisiana, United States
    • Monroe, Louisiana, United States
    • Natchitoches, Louisiana, United States
  • Maine
    • Auburn, Maine, United States
    • Bangor, Maine, United States
  • Maryland
    • Baltimore, Maryland, United States
    • Columbia, Maryland, United States
    • Elkridge, Maryland, United States
    • Lutherville, Maryland, United States
    • Salisbury, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Brockton, Massachusetts, United States
    • Fall River, Massachusetts, United States
    • Haverhill, Massachusetts, United States
    • Methuen, Massachusetts, United States
  • Michigan
    • Bingham Farms, Michigan, United States
    • Dearbon, Michigan, United States
    • Kalamazoo, Michigan, United States
    • Midland, Michigan, United States
    • Saginaw, Michigan, United States
    • Southfield, Michigan, United States
    • Stevensville, Michigan, United States
  • Minnesota
    • Edina, Minnesota, United States
    • Rochester, Minnesota, United States
  • Mississippi
    • Jackson, Mississippi, United States
    • Olive Branch, Mississippi, United States
    • Tupelo, Mississippi, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Montana
    • Butte, Montana, United States
    • Missoula, Montana, United States
  • Nebraska
    • Fremont, Nebraska, United States
    • Grand Island, Nebraska, United States
    • Omaha, Nebraska, United States
  • Nevada
    • Henderson, Nevada, United States
    • Las Vegas, Nevada, United States
    • Reno, Nevada, United States
    • Sparks, Nevada, United States
  • New Jersey
    • Belvidere, New Jersey, United States
    • Edison, New Jersey, United States
    • Elizabeth, New Jersey, United States
    • Elmer, New Jersey, United States
    • Linden, New Jersey, United States
    • Ridgewood, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Bronx, New York, United States
    • Endwell, New York, United States
    • New Hyde Park, New York, United States
    • New York, New York, United States
    • Staten Island, New York, United States
    • Syracuse, New York, United States
    • Williamsville, New York, United States
  • North Carolina
    • Cary, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Durham, North Carolina, United States
    • Elizabeth City, North Carolina, United States
    • Greensboro, North Carolina, United States
    • Greenville, North Carolina, United States
    • Hickory, North Carolina, United States
    • Morganton, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Salisbury, North Carolina, United States
    • Wilmington, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Akron, Ohio, United States
    • Beachwood, Ohio, United States
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
    • Delaware, Ohio, United States
    • Kettering, Ohio, United States
    • Marion, Ohio, United States
    • Mentor, Ohio, United States
    • Willoughby Hills, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Oregon
    • Medford, Oregon, United States
    • Portland, Oregon, United States
  • Pennsylvania
    • Altoona, Pennsylvania, United States
    • Bensalem, Pennsylvania, United States
    • Danville, Pennsylvania, United States
    • Duncansville, Pennsylvania, United States
    • Ephrata, Pennsylvania, United States
    • Jersey Shore, Pennsylvania, United States
    • Lancaster, Pennsylvania, United States
    • Lansdale, Pennsylvania, United States
    • Norristown, Pennsylvania, United States
    • Scottdale, Pennsylvania, United States
    • Sellersville, Pennsylvania, United States
    • State College, Pennsylvania, United States
    • West Reading, Pennsylvania, United States
    • Wilkes-Barre, Pennsylvania, United States
  • South Carolina
    • Anderson, South Carolina, United States
    • Charleston, South Carolina, United States
    • Columbia, South Carolina, United States
    • Greenville, South Carolina, United States
    • Greer, South Carolina, United States
    • Hodges, South Carolina, United States
    • Laurens, South Carolina, United States
    • Mount Pleasant, South Carolina, United States
  • South Dakota
    • Rapid City, South Dakota, United States
  • Tennessee
    • Bristol, Tennessee, United States
    • Chattanooga, Tennessee, United States
    • Germantown, Tennessee, United States
    • Jackson, Tennessee, United States
    • Kingsport, Tennessee, United States
    • Knoxville, Tennessee, United States
    • Memphis, Tennessee, United States
  • Texas
    • Beaumont, Texas, United States
    • Corpus Christi, Texas, United States
    • Dallas, Texas, United States
    • Houston, Texas, United States
    • Hurst, Texas, United States
    • Lake Jackson, Texas, United States
    • McKinney, Texas, United States
    • San Antonio, Texas, United States
    • Schertz, Texas, United States
    • Tomball, Texas, United States
    • Waco, Texas, United States
  • Utah
    • Bountiful, Utah, United States
    • Draper, Utah, United States
    • Murray, Utah, United States
    • Ogden, Utah, United States
    • Orem, Utah, United States
    • Salt Lake City, Utah, United States
    • West Jordan, Utah, United States
  • Virginia
    • Alexandria, Virginia, United States
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States
    • Winchester, Virginia, United States
  • Washington
    • Seattle, Washington, United States
    • Spokane, Washington, United States
    • Tacoma, Washington, United States
    • Walla Walla, Washington, United States
  • Wisconsin
    • Green Bay, Wisconsin, United States
    • Kenosha, Wisconsin, United States
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NB32	Drug: NB32; Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.; Other Names: CONTRAVE; Behavioral: Weight Management Program; 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.; Other Names: WeightMate (Tm)
Placebo Comparator: PBO	Behavioral: Weight Management Program; 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.; Other Names: WeightMate (Tm); Drug: PBO; Placebo. Administered in addition to the weight management program.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Orexigen Therapeutics, Inc

Publications and helpful links

General Publications

• Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, Perez A, Smith SR. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA. 2016 Mar 8;315(10):990-1004. doi: 10.1001/jama.2016.1558.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 14, 2012
• First Submitted That Met QC Criteria: May 16, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Actual): February 27, 2017
• Last Update Submitted That Met QC Criteria: February 24, 2017
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Obesity; Cardiovascular Diseases; Diabetes Mellitus; Overweight; Bupropion; Naltrexone; Diabetes Mellitus, Type 2; Body Weight; Narcotic Antagonists; Heart Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Nutrition Disorders; Overnutrition
• Additional Relevant MeSH Terms: Body Weight; Overweight; Anti-Obesity Agents; Bupropion hydrochloride, naltrexone hydrochoride drug combination
• Other Study ID Numbers: NB-CVOT; The Light Study (Other Identifier: Takeda); U1111-1162-4981 (Registry Identifier: WHO)