A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program

NCT ID: NCT00456521

Last Updated: 2014-12-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

793 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2008-12-31

Brief Summary

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The purpose of this study is to determine whether a combination of naltrexone SR and bupropion SR is safe and effective in treating obesity and leads to greater weight loss when given with a group lifestyle modification program than with group lifestyle modification alone.

Detailed Description

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The combination of group lifestyle modification counseling and pharmacotherapy has recently been shown to result in nearly twice the average weight loss at one year (12.1 kg) as pharmacotherapy alone (sibutramine, 5.0 kg) or lifestyle modification counseling alone (6.7 kg). Combining pharmacotherapy with a comprehensive program of diet, exercise and group lifestyle modification counseling may provide the best weight loss regimen. This study evaluated weight loss in subjects participating in such a comprehensive program who received a combination of naltrexone SR and bupropion SR, or placebo.

Conditions

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Obesity Overweight

Keywords

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Obesity Behavior Modification

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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NB32

Naltrexone SR 32 mg/ bupropion SR 360 mg/ day with intensive group lifestyle modification counseling

Group Type EXPERIMENTAL

Naltrexone SR 32 mg/ bupropion SR 360 mg/ day

Intervention Type DRUG

Intensive group lifestyle modification counseling

Intervention Type BEHAVIORAL

Placebo

Placebo with intensive group lifestyle modification counseling

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Intensive group lifestyle modification counseling

Intervention Type BEHAVIORAL

Interventions

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Naltrexone SR 32 mg/ bupropion SR 360 mg/ day

Intervention Type DRUG

Placebo

Intervention Type DRUG

Intensive group lifestyle modification counseling

Intervention Type BEHAVIORAL

Other Intervention Names

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NB32

Eligibility Criteria

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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 controlled hypertension and/or dyslipidemia
* Non-smoker and had not used tobacco or nicotine products for at least 6 months before screening
* Normotensive (systolic ≤140 mm Hg and diastolic ≤90 mm Hg). Anti-hypertensive medications were allowed with the exception of alpha-adrenergic blockers, beta-blockers, and clonidine. Medical regimen was to be stable for at least 8 weeks.
* Low-density lipoprotein level \<190 mg/dL and triglycerides level \<400 mg/dL. Medications for the treatment of dyslipidemia were allowed as long as the medical regimen had been stable for at least 8 weeks.
* No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), creatinine, bilirubin, calcium and 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
* No clinically significant abnormality on urinalysis
* Thyroid stimulating hormone (TSH) within 1.5 times ULN or normal triiodothyronine (T3), if TSH was below normal limits
* Female subjects of childbearing potential had a negative serum pregnancy test
* 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
* Completed a food diary for 6 of 7 consecutive days during screening
* 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, established polycystic ovary syndrome)
* Serious medical condition (including but not limited to renal or hepatic insufficiency; congestive heart failure, angina pectoris, myocardial infarction, stroke, claudication, or acute limb ischemia; history of malignancy with exception of non-melanoma skin cancer or surgically cured cervical cancer)
* Serious psychiatric illness (e.g., lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, and anorexia nervosa; current serious personality disorder, e.g., borderline; severe major depressive disorder, recent \[previous 6 months\] suicide attempt or current active suicidal ideation, 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
* History of drug or alcohol abuse or dependence within 1 year
* Type I or Type II diabetes mellitus
* Baseline 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) with the exception of low-dose benzodiazepine or hypnotic agents for the treatment of insomnia; any anorectic or weight loss agents; any over-the-counter dietary supplements with psychoactive, appetite or weight effects; alpha-adrenergic blockers; beta-blockers; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; topiramate, Depo-Provera®; smoking cessation agents; regular use of opioid or opioid-like analgesics
* History of surgical or device (e.g., lap band) 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
* 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 baseline
* Loss or gained \>4.0 kilograms within the previous 3 months
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Orexigen Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California, San Diego: Dept of Family & Preventive Medicine

La Jolla, California, United States

Site Status

Center for Human Nutrition, University of Colorado Health Services Center

Denver, Colorado, United States

Site Status

Univ. of Florida, College of Public Health, and Health Professions

Gainesville, Florida, United States

Site Status

Washington Univ. Center for Human Nutrition

St Louis, Missouri, United States

Site Status

New York Obesity Research Center, St. Luke's-Roosevelt Hospital Center

New York, New York, United States

Site Status

Center for Weight and Eating Disorders, School of Med., University of Penn.

Philadelphia, Pennsylvania, United States

Site Status

Center for Obesity Research and Education, Temple University

Philadelphia, Pennsylvania, United States

Site Status

Medical University of S. Carolina Weight Management Center

Charleston, South Carolina, United States

Site Status

Behavioral Medicine Research Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM, Perri MG, Pi-Sunyer FX, Rock CL, Erickson JS, Maier HN, Kim DD, Dunayevich E. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011 Jan;19(1):110-20. doi: 10.1038/oby.2010.147. Epub 2010 Jun 17.

Reference Type RESULT
PMID: 20559296 (View on PubMed)

Other Identifiers

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COR-BMOD

Identifier Type: OTHER

Identifier Source: secondary_id

NB-302

Identifier Type: -

Identifier Source: org_study_id