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

NCT00456521 | Completed Phase 3 Results DMC

• 2 other identifiers: NB-302COR-BMOD
• Study Type: interventional
• Target: 793
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Obesity; Overweight

Keywords

Obesity; Behavior Modification

Outcome Measures

Primary Outcomes (2)

• Co-primary: Body Weight- Mean Percent Change

  Baseline, 56 weeks

• Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease

  Baseline, 56 weeks

Secondary Outcomes (16)

• Body Weight- Proportion of Subjects With ≥10% Decrease

  Baseline, 56 weeks

• Change in Waist Circumference

  Baseline, 56 weeks

• Change in Fasting Triglycerides Levels, Using Log-transformed Data

  Baseline, 56 weeks

• Change in Fasting Insulin Levels, Using Log-transformed Data

  Baseline, 56 weeks

• Change in Fasting HDL Cholesterol Levels

  Baseline, 56 weeks

Study Arms (2)

NB32

EXPERIMENTAL

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

Drug: Naltrexone SR 32 mg/ bupropion SR 360 mg/ day; Behavioral: Intensive group lifestyle modification counseling

Placebo

PLACEBO COMPARATOR

Placebo with intensive group lifestyle modification counseling

Drug: Placebo; Behavioral: Intensive group lifestyle modification counseling

Interventions

Naltrexone SR 32 mg/ bupropion SR 360 mg/ day DRUG

Also known as: NB32

NB32

Placebo DRUG

Placebo

Intensive group lifestyle modification counseling BEHAVIORAL

NB32; Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (9)

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

La Jolla, California, 92093, United States

Location

Center for Human Nutrition, University of Colorado Health Services Center

Denver, Colorado, 80220, United States

Location

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

Gainesville, Florida, 32611, United States

Location

Washington Univ. Center for Human Nutrition

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10025, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

Center for Obesity Research and Education, Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of S. Carolina Weight Management Center

Charleston, South Carolina, 29425, United States

Location

Behavioral Medicine Research Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 20559296 RESULT

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

Medinfo@Orexigen.com

(858) 875-8600

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2007
• First Posted: April 5, 2007
• Study Start: March 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: December 17, 2014
• Results First Posted: November 21, 2014

Record last verified: 2014-12

Locations

US (9)