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

Obesity Clinical Trial

— INFORMUS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06098079
• Other study ID #: NB-CVOT3
• Status: Recruiting
• Phase: Phase 4
• Start date: January 3, 2024
• Est. completion date: July 2029

Study information

• Verified date: June 2024
• Source: Currax Pharmaceuticals
• Contact: Elizabeth Debnam, B.S.
• Phone: 919.805.2157
• Email: SM_INFORMUS_NB-CVOT3_External[@]syneoshealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8600
• Est. completion date: July 2029
• Est. primary completion date: January 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Naltrexone-Bupropion (NB) Combination
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Velocity Clinical Research, Abilene	Abilene	Texas
United States	Velocity Clinical Research	Albuquerque	New Mexico
United States	Velocity Clinical Research	Anderson	South Carolina
United States	Velocity Clinical Research, Gardena	Anderson	California
United States	Advanced Clinical Research Atlanta	Atlanta	Georgia
United States	Velocity Clinical Research	Austin	Texas
United States	Velocity Clinical Research	Banning	California
United States	Velocity Clinical Research	Baton Rouge	Louisiana
United States	Velocity Clinical Research	Beachwood	Ohio
United States	Advanced Cardiovascular Specialists/NextStage Clinical Research	Beaumont	Texas
United States	Velocity Clinical Research	Binghamton	New York
United States	Accel Research Sites Network	Birmingham	Alabama
United States	Velocity Clinical Research, Charleston	Charleston	South Carolina
United States	Charlottesville Medical Research	Charlottesville	Virginia
United States	Velocity Clinical Research	Chula Vista	California
United States	Velocity Clinical Research	Cincinnati	Ohio
United States	Velocity Clinical Research, Cincinnati	Cincinnati	Ohio
United States	Velocity Clinical Research, Mt. Auburn	Cincinnati	Ohio
United States	Velocity Clinical Research	Columbia	South Carolina
United States	Clincept Clinical Research	Columbus	Georgia
United States	LMG Research	Coral Gables	Florida
United States	Velocity Clinical Research	Covington	Louisiana
United States	Cullman Clinical Trials	Cullman	Alabama
United States	Dearborn Cardiology	Dearborn	Michigan
United States	Velocity Clinical Research, Durham	Durham	North Carolina
United States	Velocity Clinical Research (Providence)	East Greenwich	Rhode Island
United States	Evergreen Surgical	Eau Claire	Wisconsin
United States	Accel Research Site Network	Edgewater	Florida
United States	Velocity Clinical Research (New Smyrna Beach)	Edgewater	Florida
United States	AMR - El Dorado	El Dorado	Kansas
United States	Velocity Clinical Research, Denver	Englewood	Colorado
United States	Velocity Clinical Research	Gaffney	South Carolina
United States	NextStage Clinical Research-Chicago	Glen Ellyn	Illinois
United States	Velocity Clinical Research, Grand Island	Grand Island	Nebraska
United States	Velocity Clinical Research, Grants Pass	Grants Pass	Oregon
United States	Velocity Clinical Research	Greenville	South Carolina
United States	Velocity Clinical Research	Gulfport	Mississippi
United States	Velocity Clinical Research, Hampton	Hampton	Virginia
United States	Conveinent Medical Research	Hialeah	Florida
United States	All-American Orthopedics-NextStage Clinical Research	Houston	Texas
United States	HDH Research	Houston	Texas
United States	Velocity Clinical Research, Huntington Park	Huntington Park	California
United States	Clay Platte Family Medicine	Kansas City	Missouri
United States	Velocity Clinical Research, Kansas City	Kansas City	Kansas
United States	Velocity Clinical Research	La Mesa	California
United States	Velocity Clinical Research	Lafayette	Louisiana
United States	Healor Primary Care/CCT Research	Las Vegas	Nevada
United States	Santa Rosa Urgent Care Primary Care/CCT Research	Las Vegas	Nevada
United States	Velocity Clinical Research	Lincoln	Nebraska
United States	Velocity Clinical Research at Pioneer Heart Institute	Lincoln	Nebraska
United States	Velocity Clinical Research	Los Angeles	California
United States	NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research	Lubbock	Texas
United States	Velocity Clinical Research, Medford	Medford	Oregon
United States	Desert Clinical Research	Mesa	Arizona
United States	Activmed Practices and Research, Inc	Methuen	Massachusetts
United States	Century Research	Miami	Florida
United States	Janus Clinical Research	Miami	Florida
United States	Medical Research Center Westchester	Miami	Florida
United States	Miami Beach Clinical Research	Miami Beach	Florida
United States	Innovia Research Center	Miramar	Florida
United States	AMR Mobile	Mobile	Alabama
United States	Velocity Clinical Research, Mobile	Mobile	Alabama
United States	AMR New Orleans	New Orleans	Louisiana
United States	Velocity Clinical Research	New Orleans	Louisiana
United States	AMR Norfolk	Norfolk	Virginia
United States	Velocity Clinical Research, Norfolk	Norfolk	Nebraska
United States	Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research	North Bethesda	Maryland
United States	Coastal Carolina Research Center	North Charleston	South Carolina
United States	Meridian Clinical Research - Velocity	Omaha	Nebraska
United States	Midwest Regional Health Services	Omaha	Nebraska
United States	Velocity Clinical Research	Panorama City	California
United States	Best Choice Medical and Research Services	Pembroke Pines	Florida
United States	Mercado Medical Practice/CCT Research	Philadelphia	Pennsylvania
United States	Velocity Clinical Research, Phoenix	Phoenix	Arizona
United States	NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology	Port Arthur	Texas
United States	ActivMed Practices and Research	Portsmouth	New Hampshire
United States	Velocity Clinical Research, Portsmouth	Portsmouth	Virginia
United States	Advanced Primary Care & Geriatrics/CCT Research	Rockville	Maryland
United States	Velocity Clinical Research, Rockville	Rockville	Maryland
United States	JAELEX Research	Round Lake Beach	Illinois
United States	St. Louis Medical Professionals/CCT Research	Saint Louis	Missouri
United States	Velocity Clinical Research at Coastal Heart Medical Group	Santa Ana	California
United States	Velocity Clinical Research of Santa Ana	Santa Ana	California
United States	Axces Research Group	Santa Fe	New Mexico
United States	Velocity Clinical Research, Savannah	Savannah	Georgia
United States	Velocity Clinical Research	Sioux City	Iowa
United States	Velocity Clinical Research, Slidell	Slidell	Louisiana
United States	Velocity Clinical Research, Spartanburg	Spartanburg	South Carolina
United States	CCT Research	Tempe	Arizona
United States	NextStage Clinical Research	Tulsa	Oklahoma
United States	Velocity Clinical Research, Union	Union	South Carolina
United States	Velocity Clinical Research	Valparaiso	Indiana
United States	Velocity Clinical Research	Vestal	New York
United States	Waco Cardiology Consultants	Waco	Texas
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah
United States	AMR Wichita East	Wichita	Kansas
United States	AMR Wichita West	Wichita	Kansas
United States	Wichita Surgical Specialists	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Currax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	Comparative Rates of Cardiovascular Death	Comparative rates of cardiovascular death between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.
Secondary	Comparative Rates of Non-fatal Myocardial Infarction (MI)	Comparative rates of non-fatal MI between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.
Secondary	Comparative Rates of Non-fatal Stroke	Comparative rates of non-fatal stroke between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.