A Safety and Efficacy Study Comparing Naltrexone SR/Bupropion SR and Placebo in Obese Subjects With Type 2 Diabetes

NCT00474630 | Completed Phase 3 Results DMC

• 2 other identifiers: NB-304COR-Diabetes
• Study Type: interventional
• Target: 505
• Locations: 1 country
• Sites: 53

Brief Summary

The purpose of this study is determine whether the combination of naltrexone SR and bupropion SR is safe and effective in treating obesity in subjects with type 2 diabetes.

Conditions

Obesity; Overweight; Diabetes Mellitus, Type 2

Keywords

Obesity; Overweight; Diabetes Mellitus, Type 2

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 (23)

• Change in HbA1c Levels

  Baseline, 56 weeks

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

  Baseline, 56 weeks

• Change in Fasting HDL Cholesterol Levels

  Baseline, 56 weeks

• Change in Fasting Blood Glucose Levels

  Baseline, 56 weeks

• Change in Waist Circumference

  Baseline, 56 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 - 70 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 70 years of age (inclusive)
• Body mass index (BMI) ≥27 and ≤45 kg/m²
• Diagnosed with type 2 diabetes mellitus and on no injectable antidiabetes medication or inhaled insulin for more than 3 months prior to randomization
• Took stable doses of oral single or combination hypoglycemic medications (biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, sulfonylureas, DPP4 inhibitors) for at least 3 months prior to randomization or did not take medications for the treatment of type 2 diabetes mellitus
• Normotensive (systolic ≤145 mm Hg and diastolic ≤95 mm Hg). Antihypertensive medications were allowed with the exception of alpha-adrenergic blockers, and clonidine. Antihypertensive treatment was stable for at least 4 weeks prior to randomization.
• Medications for the treatment of dyslipidemia were allowed with the exception of cholestyramine and cholestypol as long as the medical regimen had been stable for at least 4 weeks prior to randomization.
• Free of opioid medication for 7 days prior to randomization
• HbA1c between 7% and 10%, fasting blood glucose \<270 mg/dL, and fasting triglycerides \<400 mg/dL
• No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), bilirubin, calcium, and phosphorus
• Creatinine levels were ≤1.4 mg/dL for female subjects and ≤1.5 mg/dL for male subjects
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were within 2.5 × upper limit of laboratory normal range (ULN)
• No clinically significant abnormality of hematocrit, white blood cell (WBC) count, WBC differential, or platelets
• No clinically significant abnormality on urinalysis
• TSH within normal limits or normal T3, if TSH is below normal limits
• Female subjects of childbearing potential had a negative serum pregnancy test

You may not qualify if:

• Type I diabetes mellitus
• "Brittle-diabetes" or any hospitalization or emergency room visit due to poor diabetic control within 6 months prior to screening, history of diabetes-related dehydration leading to hospitalization, or history or evidence of ketoacidosis
• Obesity of known endocrine origin other than diabetes mellitus (e.g., untreated hypothyroidism, Cushing's syndrome, established polycystic ovary syndrome)
• Diabetes mellitus secondary to pancreatitis or pancreatectomy
• Serious medical condition including but not limited to renal or hepatic insufficiency and Class III or IV congestive heart failure; history of myocardial infarction, angina pectoris, claudication, or acute limb ischemia within 6 months prior to screening; lifetime history of stroke
• History of malignancy with exception of non-melanoma skin cancer or surgically cured cervical cancer within 5 years prior to screening
• Loss or gain of more than 5.0 kg within the 3 months prior to screening
• Severe microvascular or macrovascular complications of diabetes, including but not limited to proliferative retinopathy, active limb ulcerations, amputation of metatarsals or above
• Serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, and anorexia nervosa; current serious personality disorder (e.g., borderline or antisocial); current severe major depressive disorder; recent (6 months prior to screening) suicide attempt or 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 6 months prior to screening
• History of drug or alcohol abuse or dependence within 1 year prior to screening
• Baseline ECG with a QTc interval (Bazett's formula) \>450 msec (men) and \>470 msec (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with recent myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities
• Received the following excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents, and 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 intervention for obesity (e.g., gastric banding)

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (53)

SelfCenter, PC

Fairhope, Alabama, 36532, United States

Location

Pivotal Research Centers

Peoria, Arizona, 85381, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85050, United States

Location

HealthStar Research

Hot Springs, Arkansas, 71913, United States

Location

Impact Clinical Trials

Beverly Hills, California, 90211, United States

Location

Northern California Research

Carmichael, California, 98608, United States

Location

Sierra Medical Research

Fresno, California, 93710, United States

Location

Advance Clinical Research Institute

Orange, California, 92869, United States

Location

Affiliated Research Institute

San Diego, California, 92108, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Apex Research Institue

Santa Ana, California, 92705, United States

Location

Chase Medical Research, LLC

Waterbury, Connecticut, 06708, United States

Location

LCFP Inc.

Fort Myers, Florida, 33907, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

Suncoast Clinical Research

Palm Harbor, Florida, 34684, United States

Location

University Clinical Research

Pembroke Pines, Florida, 33024, United States

Location

CSRA Partners in Health, Inc

Augusta, Georgia, 30909, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Deaconess Clinic

Evansville, Indiana, 47713, United States

Location

Northwest Indiana Center for Clinical Research

Valparaiso, Indiana, 46383, United States

Location

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, 40509, United States

Location

L-Marc

Louisville, Kentucky, 40213, United States

Location

Trover Center for Clinical Studies

Madisonville, Kentucky, 42431, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Medical Research Institute

Slidell, Louisiana, 70458, United States

Location

Health Trends Research, LLC

Baltimore, Maryland, 21209, United States

Location

FutureCare Studies

Springfield, Massachusetts, 01103, United States

Location

Twin Cities Clinical Research

Brooklyn Center, Minnesota, 55430, United States

Location

The Center for Pharmaceutical Research

Kansas City, Missouri, 64114, United States

Location

Mercy Health Research

St Louis, Missouri, 63141, United States

Location

Radiant Research, Inc.

St Louis, Missouri, 63141, United States

Location

Center for Nutrition and Metabolic Diseases, Univ. of Nevada

Reno, Nevada, 89557, United States

Location

Endocrinology & Diabetes Consultants

Dover, New Hampshire, 03820, United States

Location

Lovelace Scientific Resources

Albuquerque, New Mexico, 87108, United States

Location

Diabetes care and Information Center

Flushing, New York, 11365, United States

Location

Central New York Clinical Research

Manlius, New York, 13104, United States

Location

Rochester Clinical Research, Inc

Rochester, New York, 14609, United States

Location

Metrolina Medical Research

Charlotte, North Carolina, 28209, United States

Location

Rapid Medical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Central Ohio Nutrition Center, Inc.

Columbus, Ohio, 43213, United States

Location

Wells Institute for Health Awareness

Kettering, Ohio, 45429, United States

Location

Your Diabetes Endocrine and Nutrition Group

Mentor, Ohio, 44060, 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

ClinSearch

Chattanooga, Tennessee, 37404, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

The Cooper Institute

Dallas, Texas, 75230, United States

Location

Baylor Endocrine Center

Dallas, Texas, 75246, United States

Location

Diabetes Center of the Southwest

Midland, Texas, 79705, United States

Location

InVisions Consultants, LLC

San Antonio, Texas, 78217, United States

Location

Diabetes & Glandular Disease Research Associates, Inc.

San Antonio, Texas, 78229-4801, United States

Location

Summit Research Network, Inc.

Seattle, Washington, 98104, United States

Location

Northside Internal Medicine

Spokane, Washington, 99208, United States

Location

Related Publications (1)

• Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, Klassen P, Fujioka K; COR-Diabetes Study Group. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013 Dec;36(12):4022-9. doi: 10.2337/dc13-0234. Epub 2013 Oct 21.

  PMID: 24144653 RESULT

MeSH Terms

Conditions

Obesity; Overweight; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

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: May 15, 2007
• First Posted: May 17, 2007
• Study Start: May 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 (53)