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

NCT00567255 | Completed Phase 3 Results DMC

• 2 other identifiers: NB-303COR-II
• Study Type: interventional
• Target: 1,496
• Locations: 1 country
• Sites: 36

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.

Conditions

Obesity; Overweight

Keywords

Obesity

Outcome Measures

Primary Outcomes (2)

• Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28

  Baseline, 28 weeks

• Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28

  Baseline, 28 weeks

Secondary Outcomes (18)

• Body Weight- Mean Percent Change From Baseline to Week 56

  Baseline, 56 weeks

• Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56

  Baseline, 56 weeks

• Body Weight- Proportion of Subjects With ≥10% Decrease From Baseline to Week 28

  Baseline, 28 weeks

• Change in Waist Circumference

  Baseline, 28 weeks

• Change in Fasting HDL Cholesterol Levels

  Baseline, 28 weeks

Study Arms (2)

NB32

EXPERIMENTAL

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

Drug: Naltrexone SR 32 mg/bupropion SR 360 mg/day; Behavioral: Ancillary therapy

Placebo

PLACEBO COMPARATOR

Placebo with ancillary therapy

Drug: Placebo; Behavioral: Ancillary therapy

Interventions

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

Also known as: NB32

NB32

Placebo DRUG

Placebo

Ancillary therapy BEHAVIORAL

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

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (36)

Lovelace Scientific Resources

Phoenix, Arizona, 85016, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85050, United States

Location

HealthStar Research

Hot Springs, Arkansas, 71913, United States

Location

Northern California Research

Carmichael, California, 98608, United States

Location

Sierra Medical Research

Fresno, California, 93710, United States

Location

Pharmacology Research Institute

Newport Beach, California, 92660, United States

Location

Center for Human Nutrition University of Colorado Health Sciences Center

Denver, Colorado, 80220, United States

Location

Chase Medical Research, LLC

Waterbury, Connecticut, 06708, United States

Location

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Suncoast Clinical Research

Palm Harbor, Florida, 34684, United States

Location

Comprehensive NeuroScience, Inc

Atlanta, Georgia, 30328, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

Northwest Indiana Center for Clinical Research

Valparaiso, Indiana, 46383, United States

Location

Trover Center for Clinical Studies

Madisonville, Kentucky, 42431, United States

Location

Nutrition and Weight Mangement Center Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Milford Emergency Associates, Inc

Milford, Massachusetts, 01757, United States

Location

Summit Research Network, Inc.

Okemos, Michigan, 48864, United States

Location

Twin Cities Clinical Research

Brooklyn Center, Minnesota, 55430, United States

Location

Mercy Health Research

St Louis, Missouri, 63141, United States

Location

Radiant Research, Inc.

St Louis, Missouri, 63141, United States

Location

Clinical Research Center of Nevada

Las Vegas, Nevada, 89104, United States

Location

Endocrinology & Diabetes Consultants

Dover, New Hampshire, 03820, United States

Location

Lovelace Scientific Resources

Albuquerque, New Mexico, 87108, United States

Location

Central New York Clinical Research

Manlius, New York, 13104, United States

Location

Comprehensive Weight Control Program

New York, New York, 10021, United States

Location

Behavioral Medical Research

Staten Island, New York, 10305, United States

Location

Metrolina Medical Research

Charlotte, North Carolina, 28209, United States

Location

Patient Priority

Cincinnati, Ohio, 45242, United States

Location

Wells Institute For Health Awareness

Kettering, Ohio, 45429, United States

Location

The Portland Clinic

Portland, Oregon, 97205, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Mountain View Clinical Research

Greer, South Carolina, 29349, United States

Location

Palmetto Medical Research

Mt. Pleasant, South Carolina, 29464, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

The Cooper Institute

Dallas, Texas, 75230, United States

Location

Summit Research Network, Inc.

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  PMID: 23408728 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: November 30, 2007
• First Posted: December 4, 2007
• Study Start: December 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: November 21, 2014
• Results First Posted: November 21, 2014

Record last verified: 2014-11

Locations

US (36)