NCT01601704

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8,910

participants targeted

Target at P75+ for phase_3 obesity

Timeline
Completed

Started Jun 2012

Typical duration for phase_3 obesity

Geographic Reach
1 country

224 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 14, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 18, 2012

Completed
14 days until next milestone

Study Start

First participant enrolled

June 1, 2012

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

February 27, 2017

Completed
Last Updated

February 27, 2017

Status Verified

April 1, 2016

Enrollment Period

3.2 years

First QC Date

May 14, 2012

Results QC Date

December 11, 2016

Last Update Submit

February 24, 2017

Conditions

Keywords

Body WeightBupropionCardiovascular DiseasesDiabetes MellitusDiabetes Mellitus, Type 2Endocrine System DiseasesGlucose Metabolism DisordersHeart DiseasesMetabolic DiseasesNarcotic AntagonistsNaltrexoneNutrition DisordersObesityOvernutritionOverweight

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

  • 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

  • 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

  • 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

Study Arms (2)

NB32

EXPERIMENTAL
Drug: NB32Behavioral: Weight Management Program

PBO

PLACEBO COMPARATOR
Drug: PBOBehavioral: Weight Management Program

Interventions

NB32DRUG

Naltrexone SR 32 mg/Bupropion SR 360 mg/day. Administered in addition to the weight management program.

Also known as: CONTRAVE
NB32
PBODRUG

Placebo. Administered in addition to the weight management program.

PBO

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.

Also known as: WeightMate (Tm)
NB32PBO

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥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
  • +2 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (224)

Unknown Facility

Birmingham, Alabama, United States

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Dothan, Alabama, United States

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Mobile, Alabama, United States

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Scottsboro, Alabama, United States

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Chandler, Arizona, United States

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Mesa, Arizona, United States

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Peoria, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Tuscson, Arizona, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Carmichael, California, United States

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Escondido, California, United States

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Fresno, California, United States

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Harbor City, California, United States

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Huntington Beach, California, United States

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La Jolla, California, United States

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Lomita, California, United States

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Los Angeles, California, United States

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Paramount, California, United States

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Pasadena, California, United States

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Riverside, California, United States

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Sacramento, California, United States

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Santa Rosa, California, United States

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Spring Valley, California, United States

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Thousand Oaks, California, United States

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Torrance, California, United States

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West Hills, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Golden, Colorado, United States

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Wheat Ridge, Colorado, United States

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Norwalk, Connecticut, United States

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Stamford, Connecticut, United States

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Wilmington, Delaware, United States

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Washington D.C., District of Columbia, United States

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Boynton Beach, Florida, United States

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Brooksville, Florida, United States

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Clearwater, Florida, United States

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DeLand, Florida, United States

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Delray Beach, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville Beach, Florida, United States

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Melbourne, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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New Smyrna Beach, Florida, United States

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Oakland Park, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Pembroke Pines, Florida, United States

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Pensacola, Florida, United States

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Pinellas Park, Florida, United States

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St. Petersburg, Florida, United States

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Vero Beach, Florida, United States

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Wellington, Florida, United States

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Winter Haven, Florida, United States

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Atlanta, Georgia, United States

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Austell, Georgia, United States

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Columbus, Georgia, United States

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Lawrenceville, Georgia, United States

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Riverdale, Georgia, United States

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Savannah, Georgia, United States

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Stockbridge, Georgia, United States

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Honolulu, Hawaii, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, United States

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Melrose Park, Illinois, United States

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Bloomington, Indiana, United States

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Brownsburg, Indiana, United States

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Elwood, Indiana, United States

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Evansville, Indiana, United States

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Hammond, Indiana, United States

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South Bend, Indiana, United States

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Valparaiso, Indiana, United States

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Ames, Iowa, United States

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Council Bluffs, Iowa, United States

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Des Moines, Iowa, United States

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West Des Moines, Iowa, United States

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Overland Park, Kansas, United States

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Wichita, Kansas, United States

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Crestview Hills, Kentucky, United States

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Louisville, Kentucky, United States

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Mount Sterling, Kentucky, United States

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Alexandria, Louisiana, United States

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Baton Rouge, Louisiana, United States

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Monroe, Louisiana, United States

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Natchitoches, Louisiana, United States

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Auburn, Maine, United States

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Bangor, Maine, United States

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Baltimore, Maryland, United States

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Columbia, Maryland, United States

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Elkridge, Maryland, United States

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Lutherville, Maryland, United States

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Salisbury, Maryland, United States

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Boston, Massachusetts, United States

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Brockton, Massachusetts, United States

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Fall River, Massachusetts, United States

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Haverhill, Massachusetts, United States

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Methuen, Massachusetts, United States

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Bingham Farms, Michigan, United States

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Dearbon, Michigan, United States

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Kalamazoo, Michigan, United States

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Midland, Michigan, United States

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Saginaw, Michigan, United States

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Southfield, Michigan, United States

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Stevensville, Michigan, United States

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Edina, Minnesota, United States

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Rochester, Minnesota, United States

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Jackson, Mississippi, United States

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Olive Branch, Mississippi, United States

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Tupelo, Mississippi, United States

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St Louis, Missouri, United States

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Butte, Montana, United States

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Missoula, Montana, United States

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Fremont, Nebraska, United States

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Grand Island, Nebraska, United States

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Omaha, Nebraska, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Sparks, Nevada, United States

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Belvidere, New Jersey, United States

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Edison, New Jersey, United States

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Elizabeth, New Jersey, United States

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Elmer, New Jersey, United States

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Linden, New Jersey, United States

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Ridgewood, New Jersey, United States

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Albuquerque, New Mexico, United States

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Endwell, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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Syracuse, New York, United States

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The Bronx, New York, United States

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Williamsville, New York, United States

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Cary, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Elizabeth City, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Hickory, North Carolina, United States

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Morganton, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Akron, Ohio, United States

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Beachwood, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Delaware, Ohio, United States

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Kettering, Ohio, United States

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Marion, Ohio, United States

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Mentor, Ohio, United States

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Willoughby Hills, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Medford, Oregon, United States

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Portland, Oregon, United States

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Altoona, Pennsylvania, United States

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Bensalem, Pennsylvania, United States

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Danville, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Ephrata, Pennsylvania, United States

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Jersey Shore, Pennsylvania, United States

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Lancaster, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Scottdale, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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State College, Pennsylvania, United States

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West Reading, Pennsylvania, United States

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Wilkes-Barre, Pennsylvania, United States

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Anderson, South Carolina, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Greenville, South Carolina, United States

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Greer, South Carolina, United States

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Hodges, South Carolina, United States

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Laurens, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Bristol, Tennessee, United States

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Chattanooga, Tennessee, United States

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Germantown, Tennessee, United States

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Jackson, Tennessee, United States

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Kingsport, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Beaumont, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Hurst, Texas, United States

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Lake Jackson, Texas, United States

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McKinney, Texas, United States

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San Antonio, Texas, United States

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Schertz, Texas, United States

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Tomball, Texas, United States

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Waco, Texas, United States

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Bountiful, Utah, United States

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Draper, Utah, United States

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Murray, Utah, United States

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Ogden, Utah, United States

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Orem, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Alexandria, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Winchester, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Walla Walla, Washington, United States

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Green Bay, Wisconsin, United States

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Kenosha, Wisconsin, United States

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Madison, Wisconsin, United States

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Related Publications (1)

  • 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.

MeSH Terms

Conditions

ObesityOverweightBody WeightCardiovascular DiseasesDiabetes MellitusDiabetes Mellitus, Type 2Endocrine System DiseasesGlucose Metabolism DisordersHeart DiseasesMetabolic DiseasesNutrition DisordersOvernutrition

Interventions

bupropion hydrochloride, naltrexone hydrochoride drug combination

Condition Hierarchy (Ancestors)

Nutritional and Metabolic DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated early. Outcome measures data is based on the 50% interim analysis, designated as the primary analysis. Safety data is based on all available data at the time of database lock, which occurred after the 50% interim analysis.

Results Point of Contact

Title
Global Head of Development
Organization
Orexigen Therapeutics, Inc.

Study Officials

  • Medical Director Clinical Science

    Takeda

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 14, 2012

First Posted

May 18, 2012

Study Start

June 1, 2012

Primary Completion

August 1, 2015

Study Completion

August 1, 2015

Last Updated

February 27, 2017

Results First Posted

February 27, 2017

Record last verified: 2016-04

Locations