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Combining Naltrexone and Bupropion to Assess Cardiovascular Risks in Obese Patients

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

PHASE4 · Currax Pharmaceuticals · NCT06098079

This study is testing if a combination of two medications, naltrexone and bupropion, affects heart health in obese patients compared to a placebo while they also work on losing weight.

Quick facts

PhasePHASE4
Study typeInterventional
Enrollment8600 (estimated)
Ages18 Years and up
SexAll
SponsorCurrax Pharmaceuticals (industry)
Locations124 sites (Birmingham, Alabama and 123 other locations)
Trial IDNCT06098079 on ClinicalTrials.gov

What this trial studies

This multi-center, randomized, double-blinded, placebo-controlled study aims to evaluate the cardiovascular outcomes associated with the real-world use of a combination of naltrexone and bupropion (NB) in obese patients. Participants will be randomly assigned to receive either the NB combination or a placebo, while also being advised on weight loss through diet and exercise. The primary focus is to determine if those receiving NB are at a higher risk of major adverse cardiovascular events (MACE) compared to the placebo group. The study is designed to reflect real-world conditions and outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a BMI of 30 or higher, or 27 or higher with weight-related comorbidities, who are at increased risk for cardiovascular events.

Not a fit: Patients without obesity or overweight-related comorbidities, or those not at risk for cardiovascular disease, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the cardiovascular safety of using naltrexone and bupropion for weight management in obese patients.

How similar studies have performed: While there have been studies on the individual components, this specific combination and its cardiovascular implications in a real-world setting is relatively novel.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Birmingham, Alabama and 123 other locations

+74 more sites — see ClinicalTrials.gov for the full list.

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Obesity

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.