Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)

NCT06098079 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: NB-CVOT3
• Study Type: interventional
• Target: 8,600
• Locations: 1 country
• Sites: 140

Brief Summary

A randomized, double-blinded, placebo controlled study intended to capture cardiovascular outcomes during real-world use of naltrexone/bupropion (NB).

Conditions

Obesity

Outcome Measures

Primary Outcomes (3)

• Occurrence of Cardiovascular Death

  Occurrence of cardiovascular death in number of study patients receiving NB compared with number of study patients receiving placebo.

  Treatment initiation through 1 year following treatment termination.

• Occurrence of Non-fatal Myocardial Infarction (MI)

  Occurrence of MI in number of study patients receiving NB compared with number of study patients receiving placebo. MI will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.

  Treatment initiation through 1 year following treatment termination.

• Occurrence of Non-fatal Stroke

  Occurrence of non-fatal stroke in number of study patients receiving NB compared with number of study patients receiving placebo. Stroke will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.

  Treatment initiation through 1 year following treatment termination.

Secondary Outcomes (3)

• Comparative Rates of Cardiovascular Death

  Treatment initiation through 1 year following treatment termination.

• Comparative Rates of Non-fatal Myocardial Infarction (MI)

  Treatment initiation through 1 year following treatment termination.

• Comparative Rates of Non-fatal Stroke

  Treatment initiation through 1 year following treatment termination.

Study Arms (2)

Naltrexone/Bupropion (NB)

ACTIVE COMPARATOR

Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet.

Drug: Naltrexone-Bupropion (NB) Combination

Placebo

PLACEBO COMPARATOR

Patients will be randomly assigned to placebo.

Drug: Placebo

Interventions

Naltrexone-Bupropion (NB) Combination DRUG

A total daily dosage of two NB 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4.

Naltrexone/Bupropion (NB)

Placebo DRUG

A total daily dosage of two placebo tablets twice daily (in an identical, non-medicine containing tablet) is reached at the start of Week 4.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age ≥18 years at screening
• Able to understand the key components of the study, as described in the written informed consent document, and willing and able to provide written informed consent
• BMI ≥30 kg/m2 (obese) or ≥27 kg/m2 (overweight) in the presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia)
• At increased risk of adverse cardiovascular outcomes:
• In the opinion of the investigator, has a high likelihood of cardiovascular disease with at least 1 of the following:
• History of documented MI \>90 days prior to screening
• History of coronary revascularization (ie, coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy) \>90 days prior to screening
• History of carotid or peripheral revascularization (ie, carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass) \>90 days prior to screening
• Angina with ischemic changes (resting echocardiogram (ECHO), 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 or
• Type 2 diabetes mellitus with at least 2 of the following:
• Hypertension (controlled with or without pharmacotherapy at \<145/95 mmHg)
• Dyslipidemia requiring pharmacotherapy
• Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within the prior 12 months
• Current tobacco smoker

You may not qualify if:

• Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss
• History of MI or stroke within 90 days prior to screening
• Uncontrolled hypertension, defined as systolic BP ≥160 mmHg and/or \>100 mmHg diastolic BP on the average of 3 seated BP measurements after the patient has been at rest for at least 5 minutes
• Meets any of the following criteria:
• Confirmed end-stage renal disease (ie, a degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate \[\<15 mL/minute/1.73 m2\] and other manifestations including increased serum creatinine),
• Severe hepatic impairment (Child-Pugh score 10 to 15 \[Class C\]),
• Hemodynamic instability, including patients with severe heart failure (New York Heart Association Class IV)
• Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures
• Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin)
• Active anorexia nervosa or bulimia
• Chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opioid withdrawal or has a positive urine drug result for opioids at screening
• Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• Concomitant administration of MAOIs. This also includes use of reversible MAOIs, such as linezolid or intravenous methylene blue. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with Contrave/Mysimba.
• Subject has any disease or condition, or use of any pharmacological agent to treat the disease/condition, that, in the opinion of the investigator, would contraindicate study participation
• Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba

Sponsors & Collaborators

• Currax Pharmaceuticals: lead

Study Sites (140)

TrialMed Birmingham (DRS)

Birmingham, Alabama, 35211, United States

Location

Accel Research Sites Network

Birmingham, Alabama, 35216, United States

Location

Cullman Clinical Trials

Cullman, Alabama, 35055, United States

Location

AMR Mobile

Mobile, Alabama, 36608, United States

Location

Velocity Clinical Research, Mobile

Mobile, Alabama, 36608, United States

Location

Sun City Research

Glendale, Arizona, 85304, United States

Location

Cardiovascular Consultants/NextStage Clinical Research

Glendale, Arizona, 85306, United States

Location

Desert Clinical Research

Mesa, Arizona, 85213, United States

Location

Velocity Clinical Research, Phoenix

Phoenix, Arizona, 85006, United States

Location

Fiel Family & Sports Medicine CCT Research

Tempe, Arizona, 85283, United States

Location

Synexus Clinical Research US; Inc.

Tucson, Arizona, 85741, United States

Location

Velocity Clinical Research, Gardena

Anderson, California, 90247, United States

Location

Velocity Clinical Research

Chula Vista, California, 91911, United States

Location

Velocity Clinical Research, Huntington Park

Huntington Park, California, 90255, United States

Location

Velocity Clinical Research, San Diego

La Mesa, California, 91942, United States

Location

Chemidox Clinical Trials Inc.

Lancaster, California, 93534, United States

Location

Long Beach Clinical Trials

Long Beach, California, 90806, United States

Location

Velocity Clinical Research

Los Angeles, California, 90057, United States

Location

Valley Vitality Ventures

Manteca, California, 95350, United States

Location

National Institute of Clinical Research, Inc.

Pomona, California, 91768, United States

Location

Velocity Clinical Research, San Bernardino

San Bernardino, California, 92408, United States

Location

Velocity Clinical Research at Coastal Heart Medical Group

Santa Ana, California, 92704, United States

Location

Velocity Clinical Research of Santa Ana

Santa Ana, California, 92704, United States

Location

Velocity Clinical Research, Van Nuys

Van Nuys, California, 91405, United States

Location

Providere Research

West Covina, California, 91790, United States

Location

Velocity Clinical Research, Denver

Englewood, Colorado, 80110, United States

Location

ABMED Clinical Research

Cape Coral, Florida, 33914, United States

Location

LMG Research

Coral Gables, Florida, 33134, United States

Location

JY Research Institute

Cutler Bay, Florida, 33189, United States

Location

Delray Physician Center

Delray Beach, Florida, 33445, United States

Location

D&H Doral Research Center

Doral, Florida, 33122, United States

Location

Accel Research Sites Network - Edgewater

Edgewater, Florida, 32132, United States

Location

Velocity Clinical Research (New Smyrna Beach)

Edgewater, Florida, 32132, United States

Location

IMRC Fort Lauderdale

Fort Lauderdale, Florida, 33316, United States

Location

Southwest General Healthcare Center

Fort Myers, Florida, 33907, United States

Location

G+C Research Group

Hialeah, Florida, 33010, United States

Location

Qway Research

Hialeah, Florida, 33010, United States

Location

Conveinent Medical Research

Hialeah, Florida, 33013, United States

Location

Ilumina Medical Research

Kissimmee, Florida, 34744, United States

Location

Altus Research

Lake Worth, Florida, 33461, United States

Location

D&H Pompano Research Center, LLC

Margate, Florida, 33063, United States

Location

Optimal Research, LLC. - Melbourne

Melbourne, Florida, 32934, United States

Location

Advanced Clinical Research

Miami, Florida, 33156, United States

Location

Medical Research Center Westchester

Miami, Florida, 33165, United States

Location

Century Research

Miami, Florida, 33173, United States

Location

ITB Research

Miami, Florida, 33173, United States

Location

Entrust Clinical Research

Miami, Florida, 33176, United States

Location

Janus Clinical Research

Miami, Florida, 33186, United States

Location

Miami Beach Clinical Research

Miami Beach, Florida, 33141, United States

Location

Innovia Research Center

Miramar, Florida, 33027, United States

Location

Healix Clinical Research

New Smyrna Beach, Florida, 32168, United States

Location

Biscayne Clinical Research Inc

North Miami, Florida, 33169, United States

Location

IMRC At Palmetto Bay

Palmetto Bay, Florida, 33157, United States

Location

New Horizons Research

Palmetto Bay, Florida, 33176, United States

Location

Best Choice Medical and Research Services

Pembroke Pines, Florida, 33024, United States

Location

Bolanos Clnical Research

Pembroke Pines, Florida, 33028, United States

Location

Cordova Research Institute

Sweetwater, Florida, 33182, United States

Location

D&H Tamarac Research Center, LLC

Tamarac, Florida, 33321, United States

Location

Synexus Clinical Research US, Inc. - The Villages

The Villages, Florida, 32162, United States

Location

Advanced Clinical Research Atlanta

Atlanta, Georgia, 30309, United States

Location

Clincept Clinical Research

Columbus, Georgia, 31904, United States

Location

Accel Research Sites (ARSN) - Neurostudies

Decatur, Georgia, 30030, United States

Location

Velocity Clinical Research, Savannah

Savannah, Georgia, 31406, United States

Location

NextStage Clinical Research-Chicago

Glen Ellyn, Illinois, 60137, United States

Location

JAELEX Research

Round Lake Beach, Illinois, 60073, United States

Location

Indiana Medical Research Institute

Merriville, Indiana, 46410, United States

Location

Velocity Clinical Research

Valparaiso, Indiana, 46383, United States

Location

Velocity Clinical Research

Sioux City, Iowa, 51106, United States

Location

AMR - El Dorado

El Dorado, Kansas, 67042, United States

Location

Velocity Clinical Research, Kansas City

Kansas City, Kansas, 66210, United States

Location

AMR Wichita West

Wichita, Kansas, 67205, United States

Location

AMR Wichita East

Wichita, Kansas, 67207, United States

Location

Wichita Surgical Specialists

Wichita, Kansas, 67214, United States

Location

Velocity Clinical Research

Baton Rouge, Louisiana, 70809, United States

Location

Velocity Clinical Research

Covington, Louisiana, 70433, United States

Location

Velocity Clinical Research

Lafayette, Louisiana, 70508, United States

Location

AMR New Orleans

New Orleans, Louisiana, 70119, United States

Location

Velocity Clinical Research, New Orleans

New Orleans, Louisiana, 70119, United States

Location

Velocity Clinical Research

Slidell, Louisiana, 70458, United States

Location

Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research

North Bethesda, Maryland, 20852, United States

Location

Praveen K Gupta, MD/Avacare

Rockville, Maryland, 20852, United States

Location

Velocity Clinical Research, Rockville

Rockville, Maryland, 20854, United States

Location

Activmed Practices and Research, Inc

Methuen, Massachusetts, 01844, United States

Location

Dearborn Cardiology

Dearborn, Michigan, 48126, United States

Location

Velocity Clinical Research

Gulfport, Mississippi, 39503, United States

Location

Clay Platte Family Medicine

Kansas City, Missouri, 64151, United States

Location

St. Louis Medical Professionals/CCT Research

St Louis, Missouri, 63119, United States

Location

Velocity Clinical Research (St. Louis)

St Louis, Missouri, 63131, United States

Location

Velocity Clinical Research, Grand Island

Grand Island, Nebraska, 68803, United States

Location

Velocity Clinical Research at Pioneer Heart Institute

Lincoln, Nebraska, 68506, United States

Location

Velocity Clinical Research

Lincoln, Nebraska, 68510, United States

Location

Velocity Clinical Research, Norfolk

Norfolk, Nebraska, 68701, United States

Location

Meridian Clinical Research - Velocity

Omaha, Nebraska, 68134, United States

Location

Midwest Regional Health Services

Omaha, Nebraska, 68144, United States

Location

Avacare

Las Vegas, Nevada, 89102, United States

Location

Santa Rosa Urgent Care Primary Care/CCT Research

Las Vegas, Nevada, 89119, United States

Location

Las Vegas Clinical Trials

North Las Vegas, Nevada, 89119, United States

Location

ActivMed Practices and Research

Portsmouth, New Hampshire, 03801, United States

Location

Velocity Clinical Research

Albuquerque, New Mexico, 87107, United States

Location

Axces Research Group

Santa Fe, New Mexico, 87505, United States

Location

Velocity Clinical Research

Binghamton, New York, 13905, United States

Location

Synexus Clinical Research US, Inc. - New York

New York, New York, 10017, United States

Location

Velocity Clinical Research

Vestal, New York, 13850, United States

Location

Velocity Clinical Research, Durham

Durham, North Carolina, 27701, United States

Location

Velocity Clinical Research

Beachwood, Ohio, 44122, United States

Location

Velocity Clinical Research, Mt. Auburn

Cincinnati, Ohio, 45219, United States

Location

Velocity Clinical Research, Cincinnati

Cincinnati, Ohio, 45242, United States

Location

Velocity Clinical Research

Cincinnati, Ohio, 45246, United States

Location

NexGen Research

Lima, Ohio, 45801, United States

Location

NextStage Clinical Research - Tulsa

Tulsa, Oklahoma, 74136, United States

Location

Velocity Clinical Research, Grants Pass

Grants Pass, Oregon, 97527, United States

Location

Velocity Clinical Research, Medford

Medford, Oregon, 97504, United States

Location

Hatboro Medical Associates/Avacare Research

Horsham, Pennsylvania, 19044, United States

Location

Mercado Medical Practice/CCT Research

Philadelphia, Pennsylvania, 19111, United States

Location

Velocity Clinical Research (Providence)

East Greenwich, Rhode Island, 02818, United States

Location

Velocity Clinical Research

Anderson, South Carolina, 29621, United States

Location

Velocity Clinical Research

Charleston, South Carolina, 29414, United States

Location

Velocity Clinical Research

Columbia, South Carolina, 29204, United States

Location

Velocity Clinical Research

Gaffney, South Carolina, 29340, United States

Location

Velocity Clinical Research

Greenville, South Carolina, 29615, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Velocity Clinical Research, Spartanburg

Spartanburg, South Carolina, 29303, United States

Location

Velocity Clinical Research, Union

Union, South Carolina, 29379, United States

Location

Velocity Clinical Research, Abilene

Abilene, Texas, 79606, United States

Location

Optimal Research, LLC. - Austin

Austin, Texas, 78705, United States

Location

Velocity Clinical Research

Austin, Texas, 78759, United States

Location

Advanced Cardiovascular Specialists/NextStage Clinical Research

Beaumont, Texas, 77702, United States

Location

HDH Research

Houston, Texas, 77022, United States

Location

All-American Orthopedics-NextStage Clinical Research

Houston, Texas, 77058, United States

Location

NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research

Lubbock, Texas, 79410, United States

Location

NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology

Port Arthur, Texas, 77642, United States

Location

Synexus Clinical Research US; Inc.

San Antonio, Texas, 78229, United States

Location

Olympus Clinical Research

Sugarland, Texas, 77479, United States

Location

Waco Cardiology Consultants

Waco, Texas, 76712, United States

Location

Velocity Clinical Research, Salt Lake City

West Jordan, Utah, 84088, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Velocity Clinical Research, Hampton

Hampton, Virginia, 23666, United States

Location

AMR Norfolk

Norfolk, Virginia, 23502, United States

Location

Velocity Clinical Research, Suffolk, VA

Suffolk, Virginia, 23435, United States

Location

Evergreen Surgical

Eau Claire, Wisconsin, 54701, United States

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor will be blinded
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2023
• First Posted: October 24, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (140)