A Safety and Efficacy Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects

NCT ID: NCT00567255

Last Updated: 2014-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1496 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2009-06-30

Brief Summary

The purpose of this study is to determine whether the combination of naltrexone SR and bupropion SR is safe and effective in the treatment of obesity.

Detailed Description

Two Phase II clinical trials demonstrated that a combination of bupropion SR and naltrexone is associated with greater weight loss than naltrexone alone, bupropion SR alone or placebo in subjects with uncomplicated obesity. The current study investigated the safety and efficacy of the combination of naltrexone SR and bupropion SR compared to placebo in obese subjects with uncomplicated obesity and in those with overweight/obesity and hypertension and/or dyslipidemia.

Conditions

Obesity; Overweight

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NB32

Naltrexone SR 32 mg/bupropion SR 360 mg/day with ancillary therapy

Group Type: EXPERIMENTAL

Naltrexone SR 32 mg/bupropion SR 360 mg/day

Intervention Type: DRUG

Ancillary therapy

Intervention Type: BEHAVIORAL

Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

Placebo

Placebo with ancillary therapy

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Ancillary therapy

Intervention Type: BEHAVIORAL

Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

Interventions

Naltrexone SR 32 mg/bupropion SR 360 mg/day

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Ancillary therapy

Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

Intervention Type: BEHAVIORAL

Other Intervention Names

NB32

Eligibility Criteria

Inclusion Criteria

• Female or male subjects aged 18 to 65 years (inclusive)
• Body mass index (weight [kg]/height [m²]) ≥30 and ≤45 kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45 kg/m² for subjects with obesity with controlled hypertension and/or dyslipidemia
• Normotensive (systolic ≤140 mm Hg and diastolic ≤90 mm Hg). Anti-hypertensive medications were allowed with the exception of alpha-adrenergic blockers and clonidine. Medical regimen was to be stable for at least 6 weeks prior to randomization.
• Medications for the treatment of dyslipidemia were allowed as long as the medical regimen had been stable for at least 6 weeks prior to randomization.
• Free of opioid medication for 7 days prior to randomization
• No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 times upper limit of normal (ULN)
• No clinically significant abnormality of hematocrit, white blood cell (WBC) count, WBC differential, or platelets
• Fasting glucose <126 mg/dL and not receiving hypoglycemic agents and fasting triglycerides level <400 mg/dL
• No clinically significant abnormality on urinalysis
• Thyroid stimulating hormone (TSH) within normal limits or normal triiodothyronine (T3), if TSH was below normal limits
• Female subjects of childbearing potential had a negative serum pregnancy test
• Negative urine drug screen (UDS)
• An IDS-SR score <2 on individual items: 5 (sadness), 6 (irritability), 7 (anxiety/tension), and 18 (suicidality) and an IDS-SR total score <30
• Female subjects of childbearing potential were non-lactating and agreed to continue to use effective contraception throughout the study and 30 days after discontinuation of study drug
• Able to comply with all required study procedures and schedule
• Able to speak and read English
• Provided written informed consent

Exclusion Criteria

• Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome)
• Serious medical condition (including but not limited to renal or hepatic insufficiency; Class III or IV congestive heart failure, history of angina pectoris, myocardial infarction, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke)
• History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer
• Lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa
• Current serious psychiatric illness including severe personality disorder (e.g., borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation or recent hospitalization due to psychiatric illness
• Response to the bipolar disorder questions that indicated the presence of bipolar disorder
• Required medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization
• History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study initiation
• Type I or Type II diabetes mellitus
• Screening ECG with a corrected QT (QTc) interval (using Bazett's formula >450 millisecond (msec) [males] and >470 msec [females]) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities
• Received excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer or anticonvulsant agents or agents for the treatment of attention deficit disorder) with the exception of low-dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over the-counter dietary supplements or herbs with psychoactive, appetite or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine; cholestypol; Depo-Provera®; smoking cessation agents; use of opioid or opioid-like analgesics, including analgesics and antitussives
• History of surgical or device (e.g., gastric banding) intervention for obesity
• History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures)
• History of treatment with bupropion or naltrexone within the preceding 12 months
• History of hypersensitivity or intolerance to bupropion or naltrexone
• Initiation or discontinuation of tobacco products including inhaled tobacco (e.g., cigarettes, cigars, pipes, etc), chewing tobacco or snuff within 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (e.g., nicotine gum, patch, etc) during study participation was not allowed
• Used drugs, herbs, or dietary supplements believed to significantly affect body weight or participated in a weight loss management program within one month prior to randomization
• Loss or gained >4.0 kilograms within the previous 3 months prior to randomization
• Females who were pregnant or breast-feeding or planning to become pregnant during the study period or within 30 days of discontinuing study drug
• Planned surgical procedure that could impact the conduct of the study
• Received any investigational drug or used an experimental device or procedure within the previous 30 days
• Participated in any previous clinical trial conducted by Orexigen
• Had any condition that in the opinion of the investigator made the subject unsuitable for inclusion into the study
• Investigators, study personnel, sponsor representatives and their immediate families

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orexigen Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Lovelace Scientific Resources

Phoenix, Arizona, United States

HOPE Research Institute

Phoenix, Arizona, United States

HealthStar Research

Hot Springs, Arkansas, United States

Northern California Research

Carmichael, California, United States

Sierra Medical Research

Fresno, California, United States

Pharmacology Research Institute

Newport Beach, California, United States

Center for Human Nutrition University of Colorado Health Sciences Center

Denver, Colorado, United States

Chase Medical Research, LLC

Waterbury, Connecticut, United States

George Washington University

Washington D.C., District of Columbia, United States

Suncoast Clinical Research

Palm Harbor, Florida, United States

Comprehensive NeuroScience, Inc

Atlanta, Georgia, United States

Clinical Research Atlanta

Stockbridge, Georgia, United States

Northwest Indiana Center for Clinical Research

Valparaiso, Indiana, United States

Trover Center for Clinical Studies

Madisonville, Kentucky, United States

Nutrition and Weight Mangement Center Boston Medical Center

Boston, Massachusetts, United States

Milford Emergency Associates, Inc

Milford, Massachusetts, United States

Summit Research Network, Inc.

Okemos, Michigan, United States

Twin Cities Clinical Research

Brooklyn Center, Minnesota, United States

Mercy Health Research

St Louis, Missouri, United States

Radiant Research, Inc.

St Louis, Missouri, United States

Clinical Research Center of Nevada

Las Vegas, Nevada, United States

Endocrinology & Diabetes Consultants

Dover, New Hampshire, United States

Lovelace Scientific Resources

Albuquerque, New Mexico, United States

Central New York Clinical Research

Manlius, New York, United States

Comprehensive Weight Control Program

New York, New York, United States

Behavioral Medical Research

Staten Island, New York, United States

Metrolina Medical Research

Charlotte, North Carolina, United States

Patient Priority

Cincinnati, Ohio, United States

Wells Institute For Health Awareness

Kettering, Ohio, United States

The Portland Clinic

Portland, Oregon, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Mountain View Clinical Research

Greer, South Carolina, United States

Palmetto Medical Research

Mt. Pleasant, South Carolina, United States

Clinical Research Associates, Inc.

Nashville, Tennessee, United States

The Cooper Institute

Dallas, Texas, United States

Summit Research Network, Inc.

Seattle, Washington, United States

Countries

United States

References

Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, Kim D, Dunayevich E; COR-II Study Group. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013 May;21(5):935-43. doi: 10.1002/oby.20309.

Reference Type: RESULT

PMID: 23408728 (View on PubMed)

Other Identifiers

COR-II

Identifier Type: OTHER

Identifier Source: secondary_id

NB-303

Identifier Type: -

Identifier Source: org_study_id