Clinical trial NCT01601704: Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors (The Light Study)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Obesity
Overweight
Keywords: 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
Lead sponsor: Orexigen Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2012-05-18
Enrollment: 8910
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With a Confirmed Occurrence of Major Adverse Cardiovascular Event (MACE)
timeFrame: Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Secondary outcomes:
measure: Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death, Nonfatal Myocardial Infarction, Nonfatal Stroke, or Nonfatal Unstable Angina Requiring Hospitalization
timeFrame: Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
measure: Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death (Including Fatal Myocardial Infarction, Fatal Stroke)
timeFrame: Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
measure: Percentage of Participants With a Confirmed Occurrence of Myocardial Infarction (Nonfatal or Fatal)
timeFrame: Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
measure: Percentage of Participants With a Confirmed Occurrence of Stroke (Nonfatal or Fatal)
timeFrame: Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Dothan
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Scottsboro
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tuscson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Escondido
country: United States
state: California
city: Fresno
country: United States
state: California
city: Harbor City
country: United States
state: California
city: Huntington Beach
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Lomita
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Paramount
country: United States
state: California
city: Pasadena
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Santa Rosa
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Torrance
country: United States
state: California
city: West Hills
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Golden
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Stamford
country: United States
state: Connecticut
city: Wilmington
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Boynton Beach
country: United States
state: Florida
city: Brooksville
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Deland
country: United States
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Jacksonville Beach
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: New Smyrna Beach
country: United States
state: Florida
city: Oakland Park
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Vero beach
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Austell
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Lawrenceville
country: United States
state: Georgia
city: Riverdale
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Meridian
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Gurnee
country: United States
state: Illinois
city: Melrose Park
country: United States
state: Illinois
city: Bloomington
country: United States
state: Indiana
city: Brownsburg
country: United States
state: Indiana
city: Elwood
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Hammond
country: United States
state: Indiana
city: South Bend
country: United States
state: Indiana
city: Valparaiso
country: United States
state: Indiana
city: Ames
country: United States
state: Iowa
city: Council Bluffs
country: United States
state: Iowa
city: Des Moines
country: United States
state: Iowa
city: West Des Moines
country: United States
state: Iowa
city: Overland Park
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Crestview Hills
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Mount Sterling
country: United States
state: Kentucky
city: Alexandria
country: United States
state: Louisiana
city: Baton Rouge
country: United States
state: Louisiana
city: Monroe
country: United States
state: Louisiana
city: Natchitoches
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Bangor
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Columbia
country: United States
state: Maryland
city: Elkridge
country: United States
state: Maryland
city: Lutherville
country: United States
state: Maryland
city: Salisbury
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Brockton
country: United States
state: Massachusetts
city: Fall River
country: United States
state: Massachusetts
city: Haverhill
country: United States
state: Massachusetts
city: Methuen
country: United States
state: Massachusetts
city: Bingham Farms
country: United States
state: Michigan
city: Dearbon
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Midland
country: United States
state: Michigan
city: Saginaw
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Stevensville
country: United States
state: Michigan
city: Edina
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Olive Branch
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Missoula
country: United States
state: Montana
city: Fremont
country: United States
state: Nebraska
city: Grand Island
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Henderson
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
state: Nevada
city: Sparks
country: United States
state: Nevada
city: Belvidere
country: United States
state: New Jersey
city: Edison
country: United States
state: New Jersey
city: Elizabeth
country: United States
state: New Jersey
city: Elmer
country: United States
state: New Jersey
city: Linden
country: United States
state: New Jersey
city: Ridgewood
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Bronx
country: United States
state: New York
city: Endwell
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Williamsville
country: United States
state: New York
city: Cary
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Elizabeth City
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Morganton
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Beachwood
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Delaware
country: United States
state: Ohio
city: Kettering
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Willoughby Hills
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Bensalem
country: United States
state: Pennsylvania
city: Danville
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Ephrata
country: United States
state: Pennsylvania
city: Jersey Shore
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Norristown
country: United States
state: Pennsylvania
city: Scottdale
country: United States
state: Pennsylvania
city: Sellersville
country: United States
state: Pennsylvania
city: State College
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Wilkes-Barre
country: United States
state: Pennsylvania
city: Anderson
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Hodges
country: United States
state: South Carolina
city: Laurens
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Chattanooga
country: United States
state: Tennessee
city: Germantown
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Beaumont
country: United States
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Hurst
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: McKinney
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Schertz
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Draper
country: United States
state: Utah
city: Murray
country: United States
state: Utah
city: Ogden
country: United States
state: Utah
city: Orem
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Alexandria
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Winchester
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Walla Walla
country: United States
state: Washington
city: Green Bay
country: United States
state: Wisconsin
city: Kenosha
country: United States
state: Wisconsin
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.