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ObesityPhase 4NCT02638129

Naltrexone/Bupropion Cardiovascular Outcomes Study

A Phase 4 study testing Naltrexone HCl/Bupropion HCl ER in people with Obesity and Cardiovascular Diseases, run by Orexigen Therapeutics, Inc at 139 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Obesity, Cardiovascular Diseases
What is being tested?
Naltrexone HCl/Bupropion HCl ER
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
67 participants
Where
139 sitesUnited States
Study dates
Jan 2016to Jun 2016
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has a known infection with human immunodeficiency virus that is being treated with ritonavir, lopinavir or efavirenz.
  • Has known acute hepatitis at Screening.
  • Has chronic use of opioids, defined as longer than 3 months prior to Screening.
  • 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.
  • Has a history of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the participant to seizures.
  • 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).
  • Is at risk for suicide attempts based on the judgment of the investigator.
  • 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.
  • Has a history of severe ischemic stroke (with a Modified Rankin Scale Score ≥4).
  • 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.
  • Is unable to understand verbal or written English or any other language, for which a certified translation of the approved informed consent is available.
  • Additional exclusion criteria to be assessed at Visit3 prior to Randomization:
  • Participant takes <75% or >125% of the Lead-in study medication.
  • Participant discontinues study medication treatment or has a known major adverse cardiovascular events (MACE) reported by investigator during the Double-Blind Lead-in Period.

Trial locations and contacts

139 sites in 1 country.

139 sites in 1 country

United States139 sites

  • Study site

    Albuquerque, New Mexico

  • Study site

    Alexander City, Alabama

  • Study site

    Altoona, Pennsylvania

  • Study site

    Arlington, Texas

  • Study site

    Arvin, California

  • Study site

    Asheville, North Carolina

  • Study site

    Atlanta, Georgia

  • Study site

    Auburn, Alabama

  • Study site

    Bakersfield, California

  • Study site

    Baltimore, Maryland

  • Study site

    Baton Rouge, Louisiana

  • Study site

    Bay City, Michigan

  • Study site

    Birmingham, Alabama

  • Study site

    Blue Island, Illinois

  • Study site

    Boca Raton, Florida

  • Study site

    Bossier City, Louisiana

  • Study site

    Bountiful, Utah

  • Study site

    Bradenton, Florida

  • Study site

    Brandon, Florida

  • Study site

    Bristol, Tennessee

  • Study site

    Brooksville, Florida

  • Study site

    Camp Hill, Pennsylvania

  • Study site

    Campe Verde, Arizona

  • Study site

    Canton, Ohio

  • Study site

    Cary, North Carolina

  • Study site

    Catonsville, Maryland

  • Study site

    Chandler, Arizona

  • Study site

    Charleston, South Carolina

  • Study site

    Charleston, West Virginia

  • Study site

    Charlotte, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Chino, California

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Coral Springs, Florida

  • Study site

    Cottonwood, Arizona

  • Study site

    Cutler Bay, Florida

  • Study site

    Dallas, Texas

  • Study site

    Daytona Beach, Florida

  • Study site

    Denver, Colorado

  • Study site

    Downey, California

  • Study site

    Doylestown, Pennsylvania

  • Study site

    Duluth, Georgia

  • Study site

    Durham, North Carolina

  • Study site

    El Cajon, California

  • Study site

    Endwell, New York

  • Study site

    Evanston, Illinois

  • Study site

    Evansville, Indiana

  • Study site

    Fayetteville, Arkansas

  • Study site

    Fountain Hills, Arizona

  • Study site

    Great Falls, Montana

  • Study site

    Great Neck, New York

  • Study site

    Greenville, North Carolina

  • Study site

    Gurnee, Illinois

  • Study site

    Hazelwood, Missouri

  • Study site

    Hialeah, Florida

  • Study site

    Hickory, North Carolina

  • Study site

    Honolulu, Hawaii

  • Study site

    Houston, Texas

  • Study site

    Huntsville, Alabama

  • Study site

    Inverness, Florida

  • Study site

    Jackson, Tennessee

  • Study site

    Jacksonville Beach, Florida

  • Study site

    Jonesboro, Arkansas

  • Study site

    Katy, Texas

  • Study site

    Kenosha, Wisconsin

  • Study site

    Kingwood, Texas

  • Study site

    Knoxville, Tennessee

  • Study site

    Lake Charles, Louisiana

  • Study site

    Lake Worth, Florida

  • Study site

    Lansdale, Pennsylvania

  • Study site

    Largo, Florida

  • Study site

    Las Vegas, Nevada

  • Study site

    Linden, New Jersey

  • Study site

    Little Rock, Arkansas

  • Study site

    Los Alamitos, California

  • Study site

    Los Angeles, California

  • Study site

    Louisville, Kentucky

  • Study site

    Memphis, Tennessee

  • Study site

    Mesa, Arizona

  • Study site

    Miami Lakes, Florida

  • Study site

    Mineola, New York

  • Study site

    Moncks Corner, South Carolina

  • Study site

    Moorestown, New Jersey

  • Study site

    Morehead City, North Carolina

  • Study site

    Mt. Pleasant, South Carolina

  • Study site

    Murray, Utah

  • Study site

    New London, Connecticut

  • Study site

    New York, New York

  • Study site

    Ogden, Utah

  • Study site

    Orem, Utah

  • Study site

    Orlando, Florida

  • Study site

    Owensboro, Kentucky

  • Study site

    Palestine, Texas

  • Study site

    Palm Harbor, Florida

  • Study site

    Pembroke Pines, Florida

  • Study site

    Perrysburg, Ohio

  • Study site

    Phoenix, Arizona

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Plano, Texas

  • Study site

    Pocatello, Idaho

  • Study site

    Pomona, California

  • Study site

    Ponte Vedra Beach, Florida

  • Study site

    Port Gibson, Mississippi

  • Study site

    Port Orchard, Washington

  • Study site

    Raleigh, North Carolina

  • Study site

    Richmond, Virginia

  • Study site

    Roanoke, Virginia

  • Study site

    Rock Island, Illinois

  • Study site

    Rocky Mount, North Carolina

  • Study site

    Sacramento, California

  • Study site

    Saginaw, Michigan

  • Study site

    Salisbury, North Carolina

  • Study site

    San Antonio, Texas

  • Study site

    Sandusky, Ohio

  • Study site

    Santa Ana, California

  • Study site

    Santa Monica, California

  • Study site

    Sarasota, Florida

  • Study site

    Saratoga Springs, New York

  • Study site

    Savannah, Georgia

  • Study site

    Shreveport, Louisiana

  • Study site

    Simpsonville, South Carolina

  • Study site

    Smithfield, Pennsylvania

  • Study site

    South Ogden, Utah

  • Study site

    Stamford, Connecticut

  • Study site

    Staten Island, New York

  • Study site

    Stuart, Florida

  • Study site

    Topeka, Kansas

  • Study site

    Trumbull, Connecticut

  • Study site

    Tucson, Arizona

  • Study site

    Virginia Beach, Virginia

  • Study site

    Waterbury, Connecticut

  • Study site

    West, Utah

  • Study site

    West Jordan, Utah

  • Study site

    Willoughby, Ohio

  • Study site

    Wilmington, Delaware

  • Study site

    Winston-Salem, North Carolina

  • Study site

    Yardley, Pennsylvania

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 4 Study to Assess the Effect of Naltrexone Hydrochloride and Bupropion Hydrochloride Extended Release Combination on the Occurrence of Major Adverse Cardiovascular Events in Overweight and Obese Subjects With Cardiovascular Disease

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.

Read the detailed description

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.

Being tested
Naltrexone HCl/Bupropion HCl ER, Placebo
Keywords
Drug therapy
Medical subject headings
Obesity, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naltrexone HCl/Bupropion HCl ERDrug

    Also called Contrave

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

  • PlaceboDrug

    Naltrexone HCl/bupropion HCl placebo-matching tablets

Study groups in NCT02638129
Study groupRoleWhat they receive
Lead-In: Naltrexone/Bupropion + PlaceboOtherNaltrexone 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.
Receives: Drug: Naltrexone HCl/Bupropion HCl ER; Drug: Placebo
Lead-In: Placebo + Naltrexone/BupropionOtherNaltrexone/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.
Receives: Drug: Naltrexone HCl/Bupropion HCl ER; Drug: Placebo
Naltrexone/BupropionActive comparatorNaltrexone 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.
Receives: Drug: Naltrexone HCl/Bupropion HCl ER
PlaceboPlacebo comparatorNaltrexone/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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (3)

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

    Extended MACE defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina requiring hospitalization.

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

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

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

  3. Time From Treatment Period Randomization to the Occurrence of Cardiovascular Death

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2015 (estimated)
  2. Study startJan 2016
  3. Primary completionJun 2016
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02638129
Sponsor's protocol ID
NaltrexBuprop-4001
Other IDs
U1111-1169-1350
Status last verified
Oct 2016
First submitted
18 Dec 2015
Last updated
27 Feb 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Naltrexone HCl/Bupropion HCl ER in people with Obesity and Cardiovascular Diseases, run by Orexigen Therapeutics, Inc at 139 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 139 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time From Treatment Period Randomization to the First Confirmed Occurrence of Major Adverse Cardiovascular Events (MACE) (time frame: Day 1 to first confirmed occurrence of MACE (up to 6 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02638129.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2017.

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Naltrexone/Bupropion Cardiovascular Outcomes Study | AzTrials