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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT00532779
First received: September 19, 2007
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Obesity
Overweight
Drug: Naltrexone SR 16 mg/Bupropion SR 360 mg /day
Drug: Naltrexone SR 32 mg/Bupropion SR 360 mg /day
Drug: Placebo
Behavioral: Ancillary therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Two Doses of Naltrexone Sustained Release (SR)/Bupropion Sustained Release (SR) and Placebo in Obese Subjects

Resource links provided by NLM:


Further study details as provided by Orexigen Therapeutics, Inc:

Primary Outcome Measures:
  • Co-primary: Body Weight- Mean Percent Change [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Body Weight- Proportion of Subjects With ≥10% Decrease [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Waist Circumference [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Fasting HDL Cholesterol Levels [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Fasting Triglycerides Levels, Using Log-transformed Data [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in IWQOL-Lite Total Scores [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
    IWQOL-Lite= Impact of Weight on Quality of Life-Lite Questionnaire Total score is based on a scale from 0 to 100, with 0 representing the poorest and 100 the best quality of life and where a score of 71-79 indicates moderate impairment

  • Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Fasting Insulin Levels, Using Log-transformed Data [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Fasting Blood Glucose Levels [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in HOMA-IR Levels, Using Log-transformed Data [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
    HOMA-IR= Homeostasis Model Assessment-Insulin Resistance

  • Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
    Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult

  • Change in Fasting LDL Cholesterol Levels [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Systolic Blood Pressure [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Diastolic Blood Pressure [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in IDS-SR Total Scores [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: Yes ]
    IDS-SR= Inventory of Depressive Symptoms-Subject Rated IDS-SR total score is based on 30 items. The total score can range from 0-84, with 0 being no depressive symptoms and 84 being very severe depressive symptoms. A total score ≤ 13 indicates no depression.

  • Change in Food Craving Inventory Sweets Subscale Score [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
    The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The sweets subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).

  • Change in Food Craving Inventory Carbohydrates Subscale Score [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
    The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The carbohydrates subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).


Enrollment: 1742
Study Start Date: October 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NB16
Naltrexone SR 16 mg/Bupropion SR 360 mg /day with ancillary therapy
Drug: Naltrexone SR 16 mg/Bupropion SR 360 mg /day
Other Name: NB16
Behavioral: Ancillary therapy
Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling
Experimental: NB32
Naltrexone SR 32 mg/Bupropion SR 360 mg /day with ancillary therapy
Drug: Naltrexone SR 32 mg/Bupropion SR 360 mg /day
Other Name: NB32
Behavioral: Ancillary therapy
Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling
Placebo Comparator: Placebo
Placebo with ancillary therapy
Drug: Placebo Behavioral: Ancillary therapy
Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532779

  Hide Study Locations
Locations
United States, Alabama
Radiant Research
Birmingham, Alabama, United States, 35209
SelfCenter, PC
Fairhope, Alabama, United States, 36532
United States, Arizona
Radiant Research, Phoenix Southeast
Chandler, Arizona, United States, 85225
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
Advance Clinical Research Institute
Orange, California, United States, 92869
VA San Diego Healthcare System
San Diego, California, United States, 92161
Scripps Clinic Del Mar
San Diego, California, United States, 92130
United States, Florida
Miami Research Associates
Miami, Florida, United States, 33143
University Clinical Research
Pembroke Pines, Florida, United States, 33024
United States, Georgia
Georgia Clinical Research
Atlanta, Georgia, United States, 30308
CSRA Partners in Health, Inc
Augusta, Georgia, United States, 30909
United States, Hawaii
East-West Medical Research Institute
Honolulu, Hawaii, United States, 96814
United States, Illinois
Radiant Research
Chicago, Illinois, United States, 60610
United States, Indiana
Welborn Clinic
Evansville, Indiana, United States, 47713
United States, Kansas
Radiant Research Kansas City
Overland Park, Kansas, United States, 66202
United States, Kentucky
Central Kentucky Research Associates, Inc.
Lexington, Kentucky, United States, 40509
United States, Louisiana
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States, 70808
Medical Research Institute
Slidell, Louisiana, United States, 70458
United States, Maryland
Health Trends Research, LLC
Baltimore, Maryland, United States, 21209
United States, Massachusetts
FutureCare Studies
Springfield, Massachusetts, United States, 01103
United States, Nevada
Center for Nutrition and Metabolic Disorders
Reno, Nevada, United States, 89557
United States, North Carolina
Center for Nutrition and Preventive Medicine
Charlotte, North Carolina, United States, 28211
Wake Research Associates, LLC
Raleigh, North Carolina, United States, 27612
United States, Ohio
Rapid Medical Research, Inc.
Cleveland, Ohio, United States, 44122
Central Ohio Nutrition Center, Inc.
Columbus, Ohio, United States, 43213
United States, Oklahoma
Lynn Health Science Institute
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
Summit Research Network (Oregon), Inc.
Portland, Oregon, United States, 97210
United States, Tennessee
Internal Medicine Associates of Cordova
Cordova, Tennessee, United States, 38018
Jackson Clinic, PA
Jackson, Tennessee, United States, 38305
United States, Texas
Covance Clinical Research Unit Austin
Austin, Texas, United States, 78752
Baylor Endocrine Center
Dallas, Texas, United States, 75246
Radiant Research
Dallas, Texas, United States, 75231
Oakwell Clinical Research
San Antonio, Texas, United States, 78218
Radiant Research
San Antonio, Texas, United States, 78217
Sponsors and Collaborators
Orexigen Therapeutics, Inc
  More Information

Publications:
Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT00532779     History of Changes
Other Study ID Numbers: NB-301, COR-I
Study First Received: September 19, 2007
Results First Received: October 20, 2014
Last Updated: November 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Orexigen Therapeutics, Inc:
Obesity
Antiobesity agents
Antiobesity drugs
Overweight drug therapy
Obese drug therapy
Weight loss drug effects
Bupropion administration and dosage
Naltrexone administration and dosage
Double blind method
Combination drug therapy
Delayed action preparations

Additional relevant MeSH terms:
Obesity
Overweight
Body Weight
Nutrition Disorders
Overnutrition
Signs and Symptoms
Bupropion
Naltrexone
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014