Naltrexone/Bupropion Cardiovascular Outcomes Study

NCT02638129 | Terminated Phase 4 Results

• 2 other identifiers: NaltrexBuprop-4001U1111-1169-1350
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 139

Brief Summary

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.

Conditions

Obesity; Cardiovascular Diseases

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Time From Treatment Period Randomization to the First Confirmed Occurrence of Major Adverse Cardiovascular Events (MACE)

  MACE are defined as cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.

  Day 1 to first confirmed occurrence of MACE (up to 6 years)

Secondary Outcomes (3)

• Time From Treatment Period Randomization to the First Confirmed Occurrence of Extended Major Adverse Cardiovascular Events (MACE)

  Day 1 to first confirmed occurrence of extended MACE (up to 6 years)

• Time From Treatment Period Randomization to the Occurrence of All-Cause Death

  Day 1 to the occurrence of all-cause death (up to 6 years)

• Time From Treatment Period Randomization to the Occurrence of Cardiovascular Death

  Day 1 to the occurrence of cardiovascular death (up to 6 years)

Study Arms (4)

Lead-In: Naltrexone/Bupropion + Placebo

OTHER

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.

Drug: Naltrexone HCl/Bupropion HCl ER; Drug: Placebo

Lead-In: Placebo + Naltrexone/Bupropion

OTHER

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.

Drug: Naltrexone HCl/Bupropion HCl ER; Drug: Placebo

Naltrexone/Bupropion

ACTIVE COMPARATOR

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.

Drug: Naltrexone HCl/Bupropion HCl ER

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Naltrexone HCl/Bupropion HCl ER DRUG

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

Also known as: Contrave

Lead-In: Naltrexone/Bupropion + Placebo; Lead-In: Placebo + Naltrexone/Bupropion; Naltrexone/Bupropion

Placebo DRUG

Naltrexone HCl/bupropion HCl placebo-matching tablets

Lead-In: Naltrexone/Bupropion + Placebo; Lead-In: Placebo + Naltrexone/Bupropion; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• \. Participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• \. 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.
• \. Participant meets at least 1 the following categories of cardiovascular (CV) disease (a-c):
• Documented coronary artery disease (at least 1 of the following 2 criteria must be satisfied):
• A documented history of myocardial infarction (MI) occurring greater than 3 months prior to Screening.
• History of coronary revascularization with at least 1 of the following:
• Coronary artery bypass graft surgery occurring greater than 3 months prior to Screening.
• Percutaneous coronary intervention (PCI) occurring greater than 3 months prior to Screening.
• Documented peripheral arterial disease (at least 1 of the following 3 criteria must be satisfied):
• Current intermittent claudication or verified ischemic ulcer(s) together with documented ankle-brachial index ≤0.85.
• 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).
• 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.
• Documented cerebrovascular disease (at least 1 of the following 2 criteria must be satisfied):
• A history of transient ischemic attack confirmed by a neurologist greater than 3 months prior to Screening and clinically and neurologically stable at Screening.

You may not qualify if:

• Has received any investigational compound or investigational device within 3 months prior to Screening.
• 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.
• Has had an MI or unstable angina within 3 months of Screening.
• Has planned bariatric surgery, cardiac surgery, coronary revascularization, or peripheral artery revascularization.
• Has history of bariatric surgery (eg, Roux-en-Y gastric bypass, duodenal switch, or sleeve gastrectomy).
• 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.
• Has a history of hypersensitivity or allergies to any component of naltrexone hydrochloride (HCl) and bupropion HCl extended release combination (NB) or excipients.
• 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.
• Is hemodynamically unstable, including severe heart failure (New York Heart Association Class IV) at Screening.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to Screening.
• 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.
• Is taking excluded medications within 28 days of Screening.
• 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.
• 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.
• Has a clinical history of liver failure.

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (139)

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Alexander City, Alabama, United States

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Auburn, Alabama, United States

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Campe Verde, Arizona, United States

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Chandler, Arizona, United States

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Cottonwood, Arizona, United States

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Fountain Hills, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Fayetteville, Arkansas, United States

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Jonesboro, Arkansas, United States

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Little Rock, Arkansas, United States

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Arvin, California, United States

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Bakersfield, California, United States

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Chino, California, United States

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Downey, California, United States

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El Cajon, California, United States

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Los Alamitos, California, United States

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Los Angeles, California, United States

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Pomona, California, United States

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Sacramento, California, United States

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Santa Ana, California, United States

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Santa Monica, California, United States

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Denver, Colorado, United States

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New London, Connecticut, United States

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Stamford, Connecticut, United States

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Trumbull, Connecticut, United States

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Waterbury, Connecticut, United States

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Wilmington, Delaware, United States

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Boca Raton, Florida, United States

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Bradenton, Florida, United States

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Brandon, Florida, United States

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Brooksville, Florida, United States

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Coral Springs, Florida, United States

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Cutler Bay, Florida, United States

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Daytona Beach, Florida, United States

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Hialeah, Florida, United States

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Inverness, Florida, United States

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Jacksonville Beach, Florida, United States

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Lake Worth, Florida, United States

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Largo, Florida, United States

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Miami Lakes, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Pembroke Pines, Florida, United States

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Ponte Vedra Beach, Florida, United States

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Sarasota, Florida, United States

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Stuart, Florida, United States

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Atlanta, Georgia, United States

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Duluth, Georgia, United States

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Savannah, Georgia, United States

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Honolulu, Hawaii, United States

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Pocatello, Idaho, United States

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Blue Island, Illinois, United States

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Chicago, Illinois, United States

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Evanston, Illinois, United States

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Gurnee, Illinois, United States

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Rock Island, Illinois, United States

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Evansville, Indiana, United States

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Topeka, Kansas, United States

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Louisville, Kentucky, United States

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Owensboro, Kentucky, United States

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Baton Rouge, Louisiana, United States

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Bossier City, Louisiana, United States

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Lake Charles, Louisiana, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Catonsville, Maryland, United States

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Bay City, Michigan, United States

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Saginaw, Michigan, United States

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Port Gibson, Mississippi, United States

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Hazelwood, Missouri, United States

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Great Falls, Montana, United States

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Las Vegas, Nevada, United States

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Linden, New Jersey, United States

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Moorestown, New Jersey, United States

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Albuquerque, New Mexico, United States

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Endwell, New York, United States

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Great Neck, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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Saratoga Springs, New York, United States

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Staten Island, New York, United States

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Asheville, North Carolina, United States

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Cary, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Hickory, North Carolina, United States

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Morehead City, North Carolina, United States

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Raleigh, North Carolina, United States

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Rocky Mount, North Carolina, United States

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Salisbury, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Canton, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Perrysburg, Ohio, United States

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Sandusky, Ohio, United States

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Willoughby, Ohio, United States

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Altoona, Pennsylvania, United States

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Camp Hill, Pennsylvania, United States

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Doylestown, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Smithfield, Pennsylvania, United States

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Yardley, Pennsylvania, United States

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Charleston, South Carolina, United States

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Moncks Corner, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Simpsonville, South Carolina, United States

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Bristol, Tennessee, United States

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Jackson, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Arlington, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Katy, Texas, United States

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Kingwood, Texas, United States

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Palestine, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Murray, Utah, United States

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Ogden, Utah, United States

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Orem, Utah, United States

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South Ogden, Utah, United States

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West Jordan, Utah, United States

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West, Utah, United States

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Richmond, Virginia, United States

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Roanoke, Virginia, United States

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Virginia Beach, Virginia, United States

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Port Orchard, Washington, United States

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Charleston, West Virginia, United States

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Kenosha, Wisconsin, United States

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MeSH Terms

Conditions

Obesity; Cardiovascular Diseases

Interventions

bupropion hydrochloride, naltrexone hydrochoride drug combination

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

As this study was prematurely terminated, analysis of the primary and secondary outcome measures was not performed and analysis of safety was limited in scope.

Results Point of Contact

• Title: Global Head of Development
• Organization: Orexigen Therapeutics, Inc.

MedInfo@Orexigen.com

858-875-8600

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 22, 2015
• Study Start: January 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: February 27, 2017
• Results First Posted: February 27, 2017

Record last verified: 2016-10

Locations

US (139)