Clinical trial NCT06098079: Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)
Official title: A Phase IV Study to Assess the Effect of Naltrexone Hydrochloride Extended Release (ER) and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on the Occurrence of Major Adverse Cardiovascular Events
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Obesity
Lead sponsor: Currax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-10-24
Enrollment: 8600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

Detailed description: This multi-center, prospective, randomized, pragmatic, double-blinded study has been designed to capture cardiovascular (CV) outcomes during the real-world use of NB after initial randomization. The aim of the study is to assess whether patients receiving treatment with NB are at an elevated risk of experiencing MACE compared with patients receiving placebo. Both patient groups will also be counselled to lose weight via a reduced-calorie diet and increased physical activity.

Eligibility criteria: Inclusion Criteria:

1. Patient age ≥18 years at screening
2. 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
3. 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)
4. 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
5. Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening
6. Subject willing to comply with daily completion of an eDiary using a mobile smartphone application

Exclusion Criteria:

1. Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss
2. History of MI or stroke within 90 days prior to screening
3. 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
4. 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)
5. Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures
6. Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin)
7. Active anorexia nervosa or bulimia
8. 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
9. Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
10. 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.
11. 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
12. Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba
13. Pregnant or nursing
14. Known life-threatening arrythmias, including Brugada syndrome
15. Participation in any other concurrent investigational trial

Primary outcomes:
measure: Occurrence of Cardiovascular Death
timeFrame: Treatment initiation through 1 year following treatment termination.
measure: Occurrence of Non-fatal Myocardial Infarction (MI)
timeFrame: Treatment initiation through 1 year following treatment termination.
measure: Occurrence of Non-fatal Stroke
timeFrame: Treatment initiation through 1 year following treatment termination.
Secondary outcomes:
measure: Comparative Rates of Cardiovascular Death
timeFrame: Treatment initiation through 1 year following treatment termination.
measure: Comparative Rates of Non-fatal Myocardial Infarction (MI)
timeFrame: Treatment initiation through 1 year following treatment termination.
measure: Comparative Rates of Non-fatal Stroke
timeFrame: Treatment initiation through 1 year following treatment termination.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research Sites Network
state: Alabama
city: Cullman
country: United States
facility: Cullman Clinical Trials
state: Alabama
city: Mobile
country: United States
facility: AMR Mobile
state: Alabama
city: Mobile
country: United States
facility: Velocity Clinical Research, Mobile
state: Alabama
city: Glendale
country: United States
facility: Sun City Research
state: Arizona
city: Glendale
country: United States
facility: Cardiovascular Consultants/NextStage Clinical Research
state: Arizona
city: Mesa
country: United States
facility: Desert Clinical Research
state: Arizona
city: Phoenix
country: United States
facility: Velocity Clinical Research, Phoenix
state: Arizona
city: Tempe
country: United States
facility: Fiel Family & Sports Medicine CCT Research
state: Arizona
city: Anderson
country: United States
facility: Velocity Clinical Research, Gardena
state: California
city: Chula Vista
country: United States
facility: Velocity Clinical Research
state: California
city: Huntington Park
country: United States
facility: Velocity Clinical Research, Huntington Park
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research, San Diego
state: California
city: Lancaster
country: United States
facility: Chemidox Clinical Trials Inc.
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Research
state: California
city: Manteca
country: United States
facility: Valley Vitality Ventures
state: California
city: San Bernardino
country: United States
facility: Velocity Clinical Research, San Bernardino
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research at Coastal Heart Medical Group
state: California
city: Santa Ana
country: United States
facility: Velocity Clinical Research of Santa Ana
state: California
city: Van Nuys
country: United States
facility: Velocity Clinical Research, Van Nuys
state: California
city: West Covina
country: United States
facility: Providere Research
state: California
city: Englewood
country: United States
facility: Velocity Clinical Research, Denver
state: Colorado
city: Cape Coral
country: United States
facility: ABMED Clinical Research
state: Florida
city: Coral Gables
country: United States
facility: LMG Research
state: Florida
city: Cutler Bay
country: United States
facility: JY Research Institute
state: Florida
city: Delray Beach
country: United States
facility: Delray Physician Center
state: Florida
city: Edgewater
country: United States
facility: Accel Research Sites Network - Edgewater
state: Florida
city: Edgewater
country: United States
facility: Velocity Clinical Research (New Smyrna Beach)
state: Florida
city: Fort Lauderdale
country: United States
facility: IMRC Fort Lauderdale
state: Florida
city: Fort Myers
country: United States
facility: Southwest General Healthcare Center
state: Florida
city: Hialeah
country: United States
facility: G+C Research Group
state: Florida
city: Hialeah
country: United States
facility: Conveinent Medical Research
state: Florida
city: Kissimmee
country: United States
facility: Ilumina Medical Research
state: Florida
city: Melbourne
country: United States
facility: Optimal Research, LLC. - Melbourne
state: Florida
city: Miami Beach
country: United States
facility: Miami Beach Clinical Research
state: Florida
city: Miami
country: United States
facility: Advanced Clinical Research
state: Florida
city: Miami
country: United States
facility: Medical Research Center Westchester
state: Florida
city: Miami
country: United States
facility: Century Research
state: Florida
city: Miami
country: United States
facility: ITB Research
state: Florida
city: Miami
country: United States
facility: Entrust Clinical Research
state: Florida
city: Miami
country: United States
facility: Janus Clinical Research
state: Florida
city: Miramar
country: United States
facility: Innovia Research Center
state: Florida
city: North Miami
country: United States
facility: Biscayne Clinical Research Inc
state: Florida
city: Palmetto Bay
country: United States
facility: IMRC At Palmetto Bay
state: Florida
city: Palmetto Bay
country: United States
facility: New Horizons Research
state: Florida
city: Pembroke Pines
country: United States
facility: Best Choice Medical and Research Services
state: Florida
city: The Villages
country: United States
facility: Synexus Clinical Research US, Inc. - The Villages
state: Florida
city: Atlanta
country: United States
facility: Advanced Clinical Research Atlanta
state: Georgia
city: Columbus
country: United States
facility: Clincept Clinical Research
state: Georgia
city: Decatur
country: United States
facility: Accel Research Sites (ARSN) - Neurostudies
state: Georgia
city: Savannah
country: United States
facility: Velocity Clinical Research, Savannah
state: Georgia
city: Glen Ellyn
country: United States
facility: NextStage Clinical Research-Chicago
state: Illinois
city: Round Lake Beach
country: United States
facility: JAELEX Research
state: Illinois
city: Merriville
country: United States
facility: Indiana Medical Research Institute
state: Indiana
city: Valparaiso
country: United States
facility: Velocity Clinical Research
state: Indiana
city: Sioux City
country: United States
facility: Velocity Clinical Research
state: Iowa
city: El Dorado
country: United States
facility: AMR - El Dorado
state: Kansas
city: Kansas City
country: United States
facility: Velocity Clinical Research, Kansas City
state: Kansas
city: Wichita
country: United States
facility: AMR Wichita West
state: Kansas
city: Wichita
country: United States
facility: AMR Wichita East
state: Kansas
city: Wichita
country: United States
facility: Wichita Surgical Specialists
state: Kansas
city: Baton Rouge
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Covington
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Lafayette
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: New Orleans
country: United States
facility: AMR New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Velocity Clinical Research, New Orleans
state: Louisiana
city: Slidell
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: North Bethesda
country: United States
facility: Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research
state: Maryland
city: Rockville
country: United States
facility: Advanced Primary Care & Geriatrics/CCT Research
state: Maryland
city: Rockville
country: United States
facility: Velocity Clinical Research, Rockville
state: Maryland
city: Methuen
country: United States
facility: Activmed Practices and Research, Inc
state: Massachusetts
city: Dearborn
country: United States
facility: Dearborn Cardiology
state: Michigan
city: Gulfport
country: United States
facility: Velocity Clinical Research
state: Mississippi
city: Kansas City
country: United States
facility: Clay Platte Family Medicine
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Medical Professionals/CCT Research
state: Missouri
city: Grand Island
country: United States
facility: Velocity Clinical Research, Grand Island
state: Nebraska
city: Lincoln
country: United States
facility: Velocity Clinical Research at Pioneer Heart Institute
state: Nebraska
city: Lincoln
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Norfolk
country: United States
facility: Velocity Clinical Research, Norfolk
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research - Velocity
state: Nebraska
city: Omaha
country: United States
facility: Midwest Regional Health Services
state: Nebraska
city: Las Vegas
country: United States
facility: Healor Primary Care/CCT Research
state: Nevada
city: Las Vegas
country: United States
facility: Santa Rosa Urgent Care Primary Care/CCT Research
state: Nevada
city: North Las Vegas
country: United States
facility: Las Vegas Clinical Trials
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices and Research
state: New Hampshire
city: Albuquerque
country: United States
facility: Velocity Clinical Research
state: New Mexico
city: Santa Fe
country: United States
facility: Axces Research Group
state: New Mexico
city: Binghamton
country: United States
facility: Velocity Clinical Research
state: New York
city: New York City
country: United States
facility: Synexus Clinical Research US, Inc. - New York
state: New York
city: Vestal
country: United States
facility: Velocity Clinical Research
state: New York
city: Durham
country: United States
facility: Velocity Clinical Research, Durham
state: North Carolina
city: Beachwood
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research, Mt. Auburn
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research, Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research
state: Ohio
city: Tulsa
country: United States
facility: NextStage Clinical Research - Tulsa
state: Oklahoma
city: Grants Pass
country: United States
facility: Velocity Clinical Research, Grants Pass
state: Oregon
city: Medford
country: United States
facility: Velocity Clinical Research, Medford
state: Oregon
city: Philadelphia
country: United States
facility: Mercado Medical Practice/CCT Research
state: Pennsylvania
city: East Greenwich
country: United States
facility: Velocity Clinical Research (Providence)
state: Rhode Island
city: Anderson
country: United States
facility: Velocity Clinical Research
state: South Carolina
city: Charleston
country: United States
facility: Velocity Clinical Research
state: South Carolina
city: Columbia
country: United States
facility: Velocity Clinical Research
state: South Carolina
city: Gaffney
country: United States
facility: Velocity Clinical Research
state: South Carolina
city: Greenville
country: United States
facility: Velocity Clinical Research
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Spartanburg
country: United States
facility: Velocity Clinical Research, Spartanburg
state: South Carolina
city: Union
country: United States
facility: Velocity Clinical Research, Union
state: South Carolina
city: Abilene
country: United States
facility: Velocity Clinical Research, Abilene
state: Texas
city: Austin
country: United States
facility: Optimal Research, LLC. - Austin
state: Texas
city: Austin
country: United States
facility: Velocity Clinical Research
state: Texas
city: Beaumont
country: United States
facility: Advanced Cardiovascular Specialists/NextStage Clinical Research
state: Texas
city: Houston
country: United States
facility: HDH Research
state: Texas
city: Houston
country: United States
facility: All-American Orthopedics-NextStage Clinical Research
state: Texas
city: Lubbock
country: United States
facility: NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research
state: Texas
city: Port Arthur
country: United States
facility: NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology
state: Texas
city: Sugarland
country: United States
facility: Olympus Clinical Research
state: Texas
city: Waco
country: United States
facility: Waco Cardiology Consultants
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Hampton
country: United States
facility: Velocity Clinical Research, Hampton
state: Virginia
city: Norfolk
country: United States
facility: AMR Norfolk
state: Virginia
city: Suffolk
country: United States
facility: Velocity Clinical Research, Suffolk, VA
state: Virginia
city: Eau Claire
country: United States
facility: Evergreen Surgical
state: Wisconsin
Study officials:
References: