A Study of the Safety and Efficacy of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects

NCT ID: NCT00532779

Last Updated: 2014-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1742 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-05-31

Brief Summary

The purpose of this study is to determine whether 2 doses of the combination of naltrexone SR and bupropion SR are 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 bupropion SR alone, naltrexone alone, or placebo in subjects with uncomplicated obesity. The current study investigated the safety and efficacy of 2 doses 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

NB16

Naltrexone SR 16 mg/Bupropion SR 360 mg /day with ancillary therapy

Group Type: EXPERIMENTAL

Naltrexone SR 16 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

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 16 mg/Bupropion SR 360 mg /day

Intervention Type: DRUG

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

NB16; NB32

Eligibility Criteria

Inclusion Criteria

• Female and male subjects, 18 to 65 years of age;
• Have BMI ≥30 and ≤45kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia;
• Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine; medical regimen must be stable for at least 6 weeks prior to randomization;
• Medications for treatment of dyslipidemia are allowed as long as medical regimen has 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, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal range (ULN);
• No clinically significant abnormality of hematocrit, white blood cell (WBC) count, white cell differential, or platelets;
• Fasting glucose < 126 mg/dL on no hypoglycemic agents, fasting triglycerides <400 mg/dL;
• No clinically significant abnormality on urinalysis;
• TSH within normal limits or normal T3, if TSH is below normal limits;
• Negative serum pregnancy test in women of child-bearing potential;
• Negative urine drug screen;
• IDS-SR scores < 2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality), and IDS-SR total score < 30;
• Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;
• Able to comply with all required study procedures and schedule;
• Able to speak and read English;
• Willing and able to give written informed consent.

Exclusion Criteria

• Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome);
• Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, 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;
• A 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;
• A response to bipolar disorder questions indicating the presence of bipolar disorder;
• In need of 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 1 or Type 2 diabetes mellitus;
• Screening ECG with a corrected QT interval by the method of Bazett (QTcB) >450 msec (men) and > 470 millisecond (msec) (women) 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;
• Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, 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 medications, 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 (such as cigarettes, cigars, pipes, etc), chewing tobacco or snuff in the 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (nicotine gum, patch) during study participation was not allowed;
• Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization;
• Loss or gain of more than 4.0 kilograms within 3 months prior to randomization;
• Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug;
• Planned surgical procedure that can impact the conduct of the study;
• Use of investigational drug, device or procedure within the previous 30 days;
• Participation in any previous clinical trial sponsored by Orexigen Therapeutics;
• Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in 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

Radiant Research

Birmingham, Alabama, United States

SelfCenter, PC

Fairhope, Alabama, United States

Radiant Research, Phoenix Southeast

Chandler, Arizona, United States

Advanced Clinical Research Institute

Anaheim, California, United States

Advance Clinical Research Institute

Orange, California, United States

Scripps Clinic Del Mar

San Diego, California, United States

VA San Diego Healthcare System

San Diego, California, United States

Miami Research Associates

Miami, Florida, United States

University Clinical Research

Pembroke Pines, Florida, United States

Georgia Clinical Research

Atlanta, Georgia, United States

CSRA Partners in Health, Inc

Augusta, Georgia, United States

East-West Medical Research Institute

Honolulu, Hawaii, United States

Radiant Research

Chicago, Illinois, United States

Welborn Clinic

Evansville, Indiana, United States

Radiant Research Kansas City

Overland Park, Kansas, United States

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, United States

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Medical Research Institute

Slidell, Louisiana, United States

Health Trends Research, LLC

Baltimore, Maryland, United States

FutureCare Studies

Springfield, Massachusetts, United States

Center for Nutrition and Metabolic Disorders

Reno, Nevada, United States

Center for Nutrition and Preventive Medicine

Charlotte, North Carolina, United States

Wake Research Associates, LLC

Raleigh, North Carolina, United States

Rapid Medical Research, Inc.

Cleveland, Ohio, United States

Central Ohio Nutrition Center, Inc.

Columbus, Ohio, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Summit Research Network (Oregon), Inc.

Portland, Oregon, United States

Internal Medicine Associates of Cordova

Cordova, Tennessee, United States

Jackson Clinic, PA

Jackson, Tennessee, United States

Covance Clinical Research Unit Austin

Austin, Texas, United States

Radiant Research

Dallas, Texas, United States

Baylor Endocrine Center

Dallas, Texas, United States

Radiant Research

San Antonio, Texas, United States

Oakwell Clinical Research

San Antonio, Texas, United States

Countries

United States

References

Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. doi: 10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29.

Reference Type: RESULT

PMID: 20673995 (View on PubMed)

Other Identifiers

COR-I

Identifier Type: OTHER

Identifier Source: secondary_id

NB-301

Identifier Type: -

Identifier Source: org_study_id