- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00364871
Efficacy and Safety Study of Combination Therapy to Treat Uncomplicated Obesity
Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled Study of Combination Therapy for Safety and Efficacy in Subjects With Uncomplicated Obesity
Study Overview
Detailed Description
A completed proof of concept study, OT-101 (Data on File, Orexigen Therapeutics, 2005), demonstrated that a combination of 300 mg bupropion SR and 50 mg naltrexone was associated with greater weight loss than bupropion SR alone, naltrexone alone, or placebo in subjects with uncomplicated obesity.
The hypothesis for the current trial is that by adjusting the doses and titration schedules of bupropion SR and naltrexone greater efficacy and improved tolerability can be achieved. In this trial, a higher dose of bupropion and 2 lower doses of naltrexone than utilized in the previous trial (OT-101) will be evaluated. The doses of both drugs will be titrated over 4 weeks and administered twice a day. There are 2 cohorts. At each site, cohort 2 recruitment began as soon as cohort 1 enrollment was completed. Cohort 1 treatment groups are (60 per group):
- Group 1: Bupropion SR (400 mg/day) plus Naltrexone (48 mg/day)
- Group 2: Bupropion SR (400 mg/day) plus Naltrexone (16 mg/day)
- Group 3: Bupropion SR (400 mg/day) plus N-Placebo
- Group 4: B-placebo plus Naltrexone (48 mg/day)
- Group 5: B-Placebo plus N-Placebo
Cohort treatment 2 Groups are:
- Group 6: B-Placebo plus N-Placebo (n=20)
- Group 7: Bupropion SR (400 mg/day) plus Naltrexone (32 mg/day)(n=60)
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
San Diego, California, United States, 92130
- Scripps Clinic Del Mar
-
-
Georgia
-
Augusta, Georgia, United States, 30909
- CSRA Partners in Health, Inc
-
-
Kentucky
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Lexington, Kentucky, United States, 40536
- UK Clinical Research Organization
-
-
Louisiana
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Baton Rouge, Louisiana, United States, 70808
- Pennington Biomedical Research Center
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-
North Carolina
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Charlotte, North Carolina, United States, 28211
- Center for Nutrition and Preventive Medicine
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
South Carolina
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Charleston, South Carolina, United States, 29425
- MUSC Weight Management Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female and male subjects, 18 to 60 years of age
- Have body mass index (BMI) of 30 to 40 kg/m2
- Free from clinically significant illness or disease as determined by medical history and physical examination
- Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to baseline
- Normotensive (systolic <140 mm Hg; diastolic <90 mm Hg). Anti-hypertensive medications are allowed with the exception of adrenergic blockers, beta-blockers and clonidine. Medical regimen must be stable for at least 6 weeks
- LDL cholesterol < 190 mg/dL and triglycerides < 400 mg/dL. Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks
- No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, calcium and phosphorus
- Bilirubin, ALT and AST within 1.5 x ULN
- No clinically significant abnormality of hematocrit, white blood cell count, white cell differential, or platelets
- Fasting glucose less than 140 mg/dL on no hypoglycemic agents
- No clinically significant abnormality on urinalysis
- TSH within 1.5 x ULN, normal T3, if TSH below lower limit of normal
- Negative serum pregnancy test in women with intact uterus
- Score < 11 for depression and score < 11 for anxiety on Hospital Anxiety and Depression (HAD) Scale
- ECG: no clinically significant abnormality
- Score of zero on the Mood Assessment questionnaire and a response of "No" to the Bipolar Disorder Questions
- If female with child-bearing potential, must be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drugs
- Able to comply with all required study procedures and schedule
- Willing and able to give written informed consent
Exclusion Criteria:
- Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome)
- Serious medical condition or medical condition that limits participation in the prescribed exercise program: (e.g. unstable cardiovascular disease including congestive heart failure, angina pectoris, and myocardial infarction; stroke; claudication; acute limb ischemia; acute renal or hepatic disorder; renal, hepatic or respiratory insufficiency)
- Active malignancy or history of malignancy (other than non-melanoma skin cancer or surgically cured cervical cancer) within 5 years of enrollment
- Serious psychiatric condition (e.g., any history of bipolar disorder, psychosis, suicidal attempt or post-partum depression; a history of major depression, suicidal ideation or antidepressant use within 1 year)
- Type I or Type II diabetes mellitus requiring pharmacotherapy
- Excluded concomitant medications: anorectic agents; weight loss agents; dietary supplements to promote muscle building, enhance mood, or reduce appetite; adrenergic blockers; beta blockers; anti-psychotic agents; clonidine; theophylline; cimetidine; oral corticosteroids; anti-depressant; topiramate; Depo-Provera®, smoking cessation agents; frequent, known use of opioid or opioid-like analgesics
- History of surgical intervention for obesity
- History of seizure disorder or predisposition to seizures (e.g., history of cerebrovascular accident, significant head trauma, brain surgery, skull fracture, subdural hematoma, or febrile seizures)
- History of bulimia or anorexia nervosa
- History of drug or alcohol abuse within 5 years
- History of treatment with bupropion, or naltrexone within 12 months
- History of hypersensitivity to bupropion, or naltrexone
- Use of drugs, herbs, or dietary supplements known to significantly affect body weight within one month of baseline
- Use of investigational drug, device or procedure within 90 days
- Participation in any previous clinical trial conducted by Orexigen Therapeutics
- Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Bupropion SR (400 mg/day) plus Naltrexone (48 mg/day)
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Experimental: 2
Bupropion SR (400 mg/day) plus Naltrexone (16 mg/day)
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Active Comparator: 3
Bupropion SR (400 mg/day)
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Active Comparator: 4
Naltrexone (48 mg/day)
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Placebo Comparator: 5
B-Placebo plus N-Placebo
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Placebo Comparator: 6
B-Placebo plus N-Placebo
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
Experimental: 7
Bupropion SR (400 mg/day) plus Naltrexone (32 mg/day)
|
naltrexone 16, 32 or 48 mg/day and bupropion SR 400 mg/day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage change in total body weight
Time Frame: baseline to week 24
|
baseline to week 24
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Frank Greenway, MD, Pennington Biomedical Research Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Overnutrition
- Nutrition Disorders
- Overweight
- Body Weight
- Obesity
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Sensory System Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Narcotic Antagonists
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Alcohol Deterrents
- Dopamine Uptake Inhibitors
- Naltrexone
- Bupropion
Other Study ID Numbers
- NB201
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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