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A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT00456521
First received: April 3, 2007
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Obesity
Overweight
Drug: Naltrexone SR 32 mg/ bupropion SR 360 mg/ day
Drug: Placebo
Behavioral: Intensive group lifestyle modification counseling
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 Naltrexone Sustained Release (SR)/Bupropion SR and Placebo in Subjects With Obesity Participating in a Behavior Modification Program

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 Triglycerides 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 HDL Cholesterol Levels [ 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 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 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 Blood Glucose Levels [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
  • Change in Fasting LDL Cholesterol [ 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 Scores [ 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 Scores [ 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).

  • 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


Enrollment: 793
Study Start Date: March 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NB32
Naltrexone SR 32 mg/ bupropion SR 360 mg/ day with intensive group lifestyle modification counseling
Drug: Naltrexone SR 32 mg/ bupropion SR 360 mg/ day
Other Name: NB32
Behavioral: Intensive group lifestyle modification counseling
Placebo Comparator: Placebo
Placebo with intensive group lifestyle modification counseling
Drug: Placebo Behavioral: Intensive group lifestyle modification counseling

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Thyroid stimulating hormone (TSH) within 1.5 times ULN or normal triiodothyronine (T3), if TSH was below normal limits
  • Female subjects of childbearing potential had a negative serum pregnancy test
  • 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
  • Completed a food diary for 6 of 7 consecutive days during screening
  • Able to comply with all required study procedures and schedule
  • Able to speak and read English
  • Provided written informed consent

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
  • 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
  • Used drugs, herbs, or dietary supplements believed to significantly affect body weight or participated in a weight loss management program within one month prior to baseline
  • Loss or gained >4.0 kilograms within the previous 3 months
  • Females who were pregnant or breast-feeding or planning to become pregnant during the study period or within 30 days of discontinuing study drug
  • Planned surgical procedure that could impact the conduct of the study
  • Received any investigational drug or used an experimental device or procedure within the previous 30 days
  • Participated in any previous clinical trial conducted by Orexigen
  • Had any condition that in the opinion of the investigator made the subject unsuitable for inclusion into the study
  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: NCT00456521

Locations
United States, California
University of California, San Diego: Dept of Family & Preventive Medicine
La Jolla, California, United States, 92093
United States, Colorado
Center for Human Nutrition, University of Colorado Health Services Center
Denver, Colorado, United States, 80220
United States, Florida
Univ. of Florida, College of Public Health, and Health Professions
Gainesville, Florida, United States, 32611
United States, Missouri
Washington Univ. Center for Human Nutrition
St. Louis, Missouri, United States, 63110
United States, New York
New York Obesity Research Center, St. Luke's-Roosevelt Hospital Center
New York, New York, United States, 10025
United States, Pennsylvania
Center for Obesity Research and Education, Temple University
Philadelphia, Pennsylvania, United States, 19140
Center for Weight and Eating Disorders, School of Med., University of Penn.
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of S. Carolina Weight Management Center
Charleston, South Carolina, United States, 29425
United States, Texas
Behavioral Medicine Research Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Orexigen Therapeutics, Inc
  More Information

Publications:
Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT00456521     History of Changes
Other Study ID Numbers: NB-302, COR-BMOD
Study First Received: April 3, 2007
Results First Received: October 8, 2014
Last Updated: November 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Orexigen Therapeutics, Inc:
Obesity
Behavior Modification

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 24, 2014