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
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
A randomized, double-blinded, placebo controlled study intended to capture cardiovascular outcomes during real-world use of naltrexone/bupropion (NB).
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.
Inclusion Criteria:
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:
Type 2 diabetes mellitus with at least 2 of the following:
Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening
Subject willing to comply with daily completion of an eDiary using a mobile smartphone application
Exclusion Criteria:
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:
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
Pregnant or nursing
Known life-threatening arrythmias, including Brugada syndrome
Participation in any other concurrent investigational trial
Merriville, Indiana 46410, United States
North Bethesda, Maryland 20852, United States
Lubbock, Texas 79410, United States
Port Arthur, Texas 77642, United States
Sugarland, Texas 77479, United States