Clinical Trials/NCT00456521

NCT00456521

Completed

Phase 3

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Safety and Efficacy of Naltrexone Sustained Release (SR)/Bupropion SR and Placebo in Subjects With Obesity Participating in a Behavior Modification Program

Orexigen Therapeutics, Inc9 sites in 1 country793 target enrollmentMarch 2007

ConditionsObesity Overweight

InterventionsIntensive group lifestyle modification counseling Naltrexone SR 32 mg/ bupropion SR 360 mg/ day Placebo

DrugsNaltrexone SR 32 mg/ bupropion SR 360 mg/ day Placebo

Overview

Phase: Phase 3
Intervention: Intensive group lifestyle modification counseling
Conditions: Obesity
Sponsor: Orexigen Therapeutics, Inc
Enrollment: 793
Locations: 9
Primary Endpoint: Co-primary: Body Weight- Mean Percent Change
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

March 2007

End Date

December 2008

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Orexigen Therapeutics, Inc

Responsible Party

Sponsor

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 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

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

Arms & Interventions

Placebo

Placebo with intensive group lifestyle modification counseling

Intervention: Intensive group lifestyle modification counseling

NB32

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

Intervention: Naltrexone SR 32 mg/ bupropion SR 360 mg/ day

NB32

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

Intervention: Intensive group lifestyle modification counseling

Placebo

Placebo with intensive group lifestyle modification counseling

Intervention: Placebo

Outcomes

Primary Outcomes

Co-primary: Body Weight- Mean Percent Change

Time Frame: Baseline, 56 weeks

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

Time Frame: Baseline, 56 weeks

Secondary Outcomes

Change in Food Craving Inventory Sweets Subscale Scores(Baseline, 56 weeks)
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire(Baseline, 56 weeks)
Change in Waist Circumference(Baseline, 56 weeks)
Change in Diastolic Blood Pressure(Baseline, 56 weeks)
Change in IDS-SR Total Scores(Baseline, 56 weeks)
Body Weight- Proportion of Subjects With ≥10% Decrease(Baseline, 56 weeks)
Change in Fasting Blood Glucose Levels(Baseline, 56 weeks)
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in Systolic Blood Pressure(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)
Change in IWQOL-Lite Total Scores(Baseline, 56 weeks)
Change in HOMA-IR Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in Fasting LDL Cholesterol(Baseline, 56 weeks)
Change in Food Craving Inventory Carbohydrates Subscale Scores(Baseline, 56 weeks)