Naltrexone/Bupropion Cardiovascular Outcomes Study

NCT ID: NCT02638129

Last Updated: 2017-02-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

67 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2016-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate cardiovascular (CV) safety of naltrexone hydrochloride (HCl) and bupropion HCl extended release combination (NB) compared with placebo and rule out excess risk of major adverse cardiovascular events (MACE) when given in combination with standard of care in overweight and obese participants with documented history of CV disease.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The drug being evaluated in this study is naltrexone hydrochloride (HCl) and bupropion HCl extended release combination (NB). NB is being evaluated in this study to rule out excess cardiovascular risk. This study will evaluate the occurrence of major adverse CV events in participants who take NB compared with placebo given in combination with standard of care in overweight and obese participants with documented history of CV disease.

The study will enroll approximately 8800 patients. After a 2-week lead-in period evaluating tolerance to NB (participants were randomly assigned in a 1:1 ratio to 1 week of NB \[1 tablet per day\] followed by 1 week of placebo \[1 tablet per day\] or 1 week of placebo followed by 1 week of NB), participants will be randomly assigned to one of two treatment groups in a 1:1 ratio, which will remain undisclosed to the patient, study site personnel, and investigator/study physician during the study (unless there is an urgent medical need):

* Naltrexone HCl 8 mg/bupropion 90 mg extended release combination tablets
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants will be asked to take tablet(s) in the AM and PM at the same time each day throughout the study.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 6 years. Participants will make multiple visits to the clinic, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Obesity Cardiovascular Diseases

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lead-In: Naltrexone/Bupropion + Placebo

Naltrexone hydrochloride (HCl) 8 mg/bupropion HCl 90 mg extended release (ER) combination tablets, orally, once daily for 1 week, followed by naltrexone/bupropion placebo-matching tablets, orally, once daily for 1 week. Participants who tolerate the naltrexone/bupropion treatment and comply with taking the study medication during the Lead-In Period will be randomized to the Double-Blind Treatment Period.

Group Type OTHER

Naltrexone HCl/Bupropion HCl ER

Intervention Type DRUG

Naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets

Placebo

Intervention Type DRUG

Naltrexone HCl/bupropion HCl placebo-matching tablets

Lead-In: Placebo + Naltrexone/Bupropion

Naltrexone/bupropion placebo-matching tablets, orally, once daily, for 1 week, followed by naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets, orally, once daily, for 1 week. Participants who tolerate the naltrexone/bupropion treatment and comply with taking the study medication during the Lead-In Period will be randomized to the Double-Blind Treatment Period.

Group Type OTHER

Naltrexone HCl/Bupropion HCl ER

Intervention Type DRUG

Naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets

Placebo

Intervention Type DRUG

Naltrexone HCl/bupropion HCl placebo-matching tablets

Naltrexone/Bupropion

Naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets, orally, one tablet, in the morning (AM), daily, for 1 week, followed by naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets, orally, one tablet in the AM and one in the evening (PM), daily, for 1 week, followed by naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets, orally, two tablets in the AM and one in the PM, daily, for 1 week, followed by naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets, orally, two tablets in the AM and two in the PM, daily, for up to 6 years.

Group Type ACTIVE_COMPARATOR

Naltrexone HCl/Bupropion HCl ER

Intervention Type DRUG

Naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets

Placebo

Naltrexone/bupropion placebo-matching tablets, orally, one tablet in the AM, daily, for 1 week, followed by naltrexone/bupropion placebo-matching tablets, orally, one tablet in the AM and one in the PM, daily, for 1 week, followed by naltrexone/bupropion placebo-matching tablets, orally, two tablets in the AM and one in the PM, daily, for 1 week, followed by naltrexone/bupropion placebo-matching tablets, orally, two tablets in the AM and two in the PM, daily, for up to 6 years.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Naltrexone HCl/bupropion HCl placebo-matching tablets

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Naltrexone HCl/Bupropion HCl ER

Naltrexone HCl 8 mg/bupropion HCl 90 mg ER combination tablets

Intervention Type DRUG

Placebo

Naltrexone HCl/bupropion HCl placebo-matching tablets

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Contrave

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1\. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2\. Participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3\. Has body mass index (BMI) ≥27.0 kg/m\^2 at Screening. 4. Is male or female and aged ≥18 years at Screening. 5. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent through 12 weeks after the last dose of study medication.

6\. Participant meets at least 1 the following categories of cardiovascular (CV) disease (a-c):

1. Documented coronary artery disease (at least 1 of the following 2 criteria must be satisfied):

1. A documented history of myocardial infarction (MI) occurring greater than 3 months prior to Screening.
2. History of coronary revascularization with at least 1 of the following:

1. Coronary artery bypass graft surgery occurring greater than 3 months prior to Screening.
2. Percutaneous coronary intervention (PCI) occurring greater than 3 months prior to Screening.
2. Documented peripheral arterial disease (at least 1 of the following 3 criteria must be satisfied):

1. Current intermittent claudication or verified ischemic ulcer(s) together with documented ankle-brachial index ≤0.85.
2. History of previous vascular intervention for intermittent claudication or resting limb ischemia greater than 3 months prior to Screening (example: amputation for arterial disease, peripheral bypass, or history of angioplasty/stenting).
3. History of symptomatic carotid artery disease (requiring revascularization with carotid endarterectomy or stenting) greater than 3 months prior to Screening or ≥50% stenosis on at least one carotid artery documented by duplex ultrasonography, magnetic resonance angiography, computed tomographic angiography, or catheter-based contrast angiography.
3. Documented cerebrovascular disease (at least 1 of the following 2 criteria must be satisfied):

1. A history of transient ischemic attack confirmed by a neurologist greater than 3 months prior to Screening and clinically and neurologically stable at Screening.
2. A history of ischemic stroke (with a Modified Rankin Scale Score ≤3) greater than 3 months prior to Screening and clinically and neurologically stable at Screening.

Exclusion Criteria

1. Has received any investigational compound or investigational device within 3 months prior to Screening.
2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
3. Has had an MI or unstable angina within 3 months of Screening.
4. Has planned bariatric surgery, cardiac surgery, coronary revascularization, or peripheral artery revascularization.
5. Has history of bariatric surgery (eg, Roux-en-Y gastric bypass, duodenal switch, or sleeve gastrectomy).
6. Has had a procedure for weight loss other than bariatric surgery (eg, gastric banding or any other devices that maybe used in obesity treatment) within past 12 months prior to Screening.
7. Has a history of hypersensitivity or allergies to any component of naltrexone hydrochloride (HCl) and bupropion HCl extended release combination (NB) or excipients.
8. Has a history of cancer that has been in remission for \<5 years prior to Screening. A history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed.
9. Is hemodynamically unstable, including severe heart failure (New York Heart Association Class IV) at Screening.
10. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
11. Has been randomized into a previous NB (Contrave) study or has been exposed to commercially available NB (Contrave) for any period of time prior to Screening.
12. Is taking excluded medications within 28 days of Screening.
13. Has uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mm Hg and/or ≥100 mm Hg diastolic blood pressure (DBP) on the average of two seated blood pressure measurements after being at rest at least 5 minutes, confirmed on 2 separate days during the Screening Period.
14. Has severe renal impairment defined by estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73 m\^2 based on the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) at Screening.
15. Has a clinical history of liver failure.
16. Has a known infection with human immunodeficiency virus that is being treated with ritonavir, lopinavir or efavirenz.
17. Has known acute hepatitis at Screening.
18. Has chronic use of opioids, defined as longer than 3 months prior to Screening.
19. Has a positive drug screen for cocaine, methamphetamine, methadone, opiates, oxycodone, phencyclidine, and propoxyphene at Screening. A positive screen for amphetamines, barbiturates, benzodiazepines, and cannabinoids is exclusionary if abuse or dependence is suspected.
20. Has a history of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the participant to seizures.
21. Has a history of mania, history of or current diagnosis of bipolar disorder or current diagnosis of active psychosis, active bulimia or anorexia nervosa (binge eating disorder is not exclusionary).
22. Is at risk for suicide attempts based on the judgment of the investigator.
23. If female, the participant is pregnant (confirmed by laboratory testing at screening) or lactating or intending to become pregnant from signing the informed consent through 12 weeks after last dose of study medication; or intending to donate ova during such time period.
24. Has a history of severe ischemic stroke (with a Modified Rankin Scale Score ≥4).
25. Has any major illness or condition that, in the investigator's opinion, prohibits the participant from participating in the study or meeting the planned visit schedule.
26. Is unable to understand verbal or written English or any other language, for which a certified translation of the approved informed consent is available.


1. Participant takes \<75% or \>125% of the Lead-in study medication.
2. Participant discontinues study medication treatment or has a known major adverse cardiovascular events (MACE) reported by investigator during the Double-Blind Lead-in Period.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Orexigen Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Alexander City, Alabama, United States

Site Status

Auburn, Alabama, United States

Site Status

Birmingham, Alabama, United States

Site Status

Huntsville, Alabama, United States

Site Status

Campe Verde, Arizona, United States

Site Status

Chandler, Arizona, United States

Site Status

Cottonwood, Arizona, United States

Site Status

Fountain Hills, Arizona, United States

Site Status

Mesa, Arizona, United States

Site Status

Phoenix, Arizona, United States

Site Status

Tucson, Arizona, United States

Site Status

Fayetteville, Arkansas, United States

Site Status

Jonesboro, Arkansas, United States

Site Status

Little Rock, Arkansas, United States

Site Status

Arvin, California, United States

Site Status

Bakersfield, California, United States

Site Status

Chino, California, United States

Site Status

Downey, California, United States

Site Status

El Cajon, California, United States

Site Status

Los Alamitos, California, United States

Site Status

Los Angeles, California, United States

Site Status

Pomona, California, United States

Site Status

Sacramento, California, United States

Site Status

Santa Ana, California, United States

Site Status

Santa Monica, California, United States

Site Status

Denver, Colorado, United States

Site Status

New London, Connecticut, United States

Site Status

Stamford, Connecticut, United States

Site Status

Trumbull, Connecticut, United States

Site Status

Waterbury, Connecticut, United States

Site Status

Wilmington, Delaware, United States

Site Status

Boca Raton, Florida, United States

Site Status

Bradenton, Florida, United States

Site Status

Brandon, Florida, United States

Site Status

Brooksville, Florida, United States

Site Status

Coral Springs, Florida, United States

Site Status

Cutler Bay, Florida, United States

Site Status

Daytona Beach, Florida, United States

Site Status

Hialeah, Florida, United States

Site Status

Inverness, Florida, United States

Site Status

Jacksonville Beach, Florida, United States

Site Status

Lake Worth, Florida, United States

Site Status

Largo, Florida, United States

Site Status

Miami Lakes, Florida, United States

Site Status

Orlando, Florida, United States

Site Status

Palm Harbor, Florida, United States

Site Status

Pembroke Pines, Florida, United States

Site Status

Ponte Vedra Beach, Florida, United States

Site Status

Sarasota, Florida, United States

Site Status

Stuart, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Duluth, Georgia, United States

Site Status

Savannah, Georgia, United States

Site Status

Honolulu, Hawaii, United States

Site Status

Pocatello, Idaho, United States

Site Status

Blue Island, Illinois, United States

Site Status

Chicago, Illinois, United States

Site Status

Evanston, Illinois, United States

Site Status

Gurnee, Illinois, United States

Site Status

Rock Island, Illinois, United States

Site Status

Evansville, Indiana, United States

Site Status

Topeka, Kansas, United States

Site Status

Louisville, Kentucky, United States

Site Status

Owensboro, Kentucky, United States

Site Status

Baton Rouge, Louisiana, United States

Site Status

Bossier City, Louisiana, United States

Site Status

Lake Charles, Louisiana, United States

Site Status

Shreveport, Louisiana, United States

Site Status

Baltimore, Maryland, United States

Site Status

Catonsville, Maryland, United States

Site Status

Bay City, Michigan, United States

Site Status

Saginaw, Michigan, United States

Site Status

Port Gibson, Mississippi, United States

Site Status

Hazelwood, Missouri, United States

Site Status

Great Falls, Montana, United States

Site Status

Las Vegas, Nevada, United States

Site Status

Linden, New Jersey, United States

Site Status

Moorestown, New Jersey, United States

Site Status

Albuquerque, New Mexico, United States

Site Status

Endwell, New York, United States

Site Status

Great Neck, New York, United States

Site Status

Mineola, New York, United States

Site Status

New York, New York, United States

Site Status

Saratoga Springs, New York, United States

Site Status

Staten Island, New York, United States

Site Status

Asheville, North Carolina, United States

Site Status

Cary, North Carolina, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Durham, North Carolina, United States

Site Status

Greenville, North Carolina, United States

Site Status

Hickory, North Carolina, United States

Site Status

Morehead City, North Carolina, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Rocky Mount, North Carolina, United States

Site Status

Salisbury, North Carolina, United States

Site Status

Winston-Salem, North Carolina, United States

Site Status

Canton, Ohio, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Cleveland, Ohio, United States

Site Status

Columbus, Ohio, United States

Site Status

Perrysburg, Ohio, United States

Site Status

Sandusky, Ohio, United States

Site Status

Willoughby, Ohio, United States

Site Status

Altoona, Pennsylvania, United States

Site Status

Camp Hill, Pennsylvania, United States

Site Status

Doylestown, Pennsylvania, United States

Site Status

Lansdale, Pennsylvania, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Smithfield, Pennsylvania, United States

Site Status

Yardley, Pennsylvania, United States

Site Status

Charleston, South Carolina, United States

Site Status

Moncks Corner, South Carolina, United States

Site Status

Mt. Pleasant, South Carolina, United States

Site Status

Simpsonville, South Carolina, United States

Site Status

Bristol, Tennessee, United States

Site Status

Jackson, Tennessee, United States

Site Status

Knoxville, Tennessee, United States

Site Status

Memphis, Tennessee, United States

Site Status

Arlington, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Houston, Texas, United States

Site Status

Katy, Texas, United States

Site Status

Kingwood, Texas, United States

Site Status

Palestine, Texas, United States

Site Status

Plano, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

Bountiful, Utah, United States

Site Status

Murray, Utah, United States

Site Status

Ogden, Utah, United States

Site Status

Orem, Utah, United States

Site Status

South Ogden, Utah, United States

Site Status

West Jordan, Utah, United States

Site Status

West, Utah, United States

Site Status

Richmond, Virginia, United States

Site Status

Roanoke, Virginia, United States

Site Status

Virginia Beach, Virginia, United States

Site Status

Port Orchard, Washington, United States

Site Status

Charleston, West Virginia, United States

Site Status

Kenosha, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U1111-1169-1350

Identifier Type: REGISTRY

Identifier Source: secondary_id

NaltrexBuprop-4001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Buprenorphine Naltrexone-P1 A-Cocaine
NCT00733720 COMPLETED PHASE1