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Sponsored by: |
Orexigen Therapeutics, Inc |
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Information provided by: | Orexigen Therapeutics, Inc |
ClinicalTrials.gov Identifier: | NCT00339014 |
The purpose of this study is to determine which of seven combinations of Zonisamide CR and Bupropion SR gives the best weight loss and is safe and well tolerated for the treatment of obesity not associated with the complications of obesity such as diabetes. In a previous study, the combination of zonisamide and bupropion SR was shown to be effective for weight loss compared to either zonisamide, bupropion SR alone or placebo. It is thought that by adjusting the doses of each drug, giving zonisamide in a controlled release (CR) form and increasing the doses more slowly, more weight loss and less side effects can be attained.
Condition | Intervention | Phase |
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Obesity |
Drug: Zonisamide CR and Bupropion SR Other: Placebo |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Dose Parallel, Randomized, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of Multiple Regimens of the Combination of Zonisamide CR Plus Bupropion SR in the Treatment of Subjects With Uncomplicated Obesity |
Enrollment: | 611 |
Study Start Date: | May 2006 |
Study Completion Date: | August 2007 |
Primary Completion Date: | August 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Group 1: Active Comparator
Zonisamide SR 120 mg/day plus Bupropion SR 280 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 2: Active Comparator
Zonisamide SR 120 mg/day plus Bupropion SR 360 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 3: Active Comparator
Zonisamide SR 240 mg/day plus Bupropion SR 280 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 4: Active Comparator
Zonisamide SR 240 mg/day plus Bupropion SR 360 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 5: Active Comparator
Zonisamide SR 360 mg/day plus Bupropion SR 280 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 6: Active Comparator
Zonisamide SR 360 mg/day plus Bupropion SR 360 mg/day
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Drug: Zonisamide CR and Bupropion SR
Zonisamide SR and Bupropion SR
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Group 7: Placebo Comparator |
Other: Placebo
Identical placebo
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Over the past few years, knowledge of the pathways and neural circuits that sense body energy stores has increased dramatically. In particular, it has been shown that the melanocortin system, a group of neuronal circuits in the arcuate nucleus of the hypothalamus, is the "final common pathway" for most energy state signals, and that melanocortin signaling is necessary for normal control of food intake and energy expenditure. Stimulation of POMC neurons by serotonergic and dopaminergic agents results in release of α-, β- and γ-MSH through the action of prohormone convertase-2 with a consequent decrease in appetite.A second counter-regulatory system that inhibits POMC activation is β-endorphin, which binds to a mu-opioid receptor (MOP-R) and acts as an auto-inhibitory "brake" on the activity of the melanocortin circuits. Bupropion is an approved antidepressant that blocks reuptake of serotonin and dopamine. This stimulates secretion of both α -MSH and β-endorphin. α -MSH binds to melanocortin receptors which in turn results in appetite suppression and increased energy expenditure. β-endorphin, however, binds to a mu-opioid receptor (MOP-R) and inhibits the activity of the melanocortin circuits. Zonisamide has multiple effects that may protect against seizures, including blockade of sodium channels, and reducing voltage dependent inward (T type) calcium currents, leading to neuronal stabilization. In addition to these actions, however, it is known to increase 5-hydroxytryptophan and dopamine levels, simultaneously stimulating α -MSH release while inhibiting AGRP release. Thus, the combination of bupropion and zonisamide stimulates the melanocortin system while blocking an important feedback inhibitory pathway.
The combination of zonisamide 400 mg/day and bupropion SR 300 mg/day has been shown to be more effective for weight loss than either monotherapy or placebo in subjects with uncomplicated obesity. The hypothesis for the current trial is that greater efficacy and improved tolerability can be achieved by adjusting the doses and titration of both bupropion SR and zonisamide, and by giving zonisamide in a controlled release (CR) formulation.
Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Alabama | |
SelfCenter, PC | |
Fairhope, Alabama, United States, 36532 | |
United States, California | |
Scripps Clinic Del Mar | |
San Diego, California, United States, 92130 | |
UCLA Center for Human Nutrition | |
Los Angeles, California, United States, 90095 | |
United States, Colorado | |
Center for Human Nutrition University of Colorado Health Sciences Center | |
Denver, Colorado, United States, 80220 | |
United States, District of Columbia | |
George Washington University Weight Management Program | |
Washington, District of Columbia, United States, 20037 | |
United States, Georgia | |
CSRA Partners in Health, Inc | |
Augusta, Georgia, United States, 30909 | |
United States, Illinois | |
Springfield Diabetes and Endocrine Center | |
Springfield, Illinois, United States, 62704 | |
United States, Louisiana | |
Pennington Biomedical Research Center | |
Baton Rouge, Louisiana, United States, 70808 | |
United States, Massachusetts | |
Nutrition and Weight Mangement Center Boston Medical Center | |
Boston, Massachusetts, United States, 02118 | |
United States, Nevada | |
Center for Nutrition and Metabolic Diseases | |
Reno, Nevada, United States, 89557 | |
United States, New York | |
Comprehensive Weight Control Program | |
New York, New York, United States, 10021 | |
United States, North Carolina | |
Center for Nutrition and Preventive Medicine | |
Charlotte, North Carolina, United States, 28211 | |
United States, South Carolina | |
MUSC Weight Mnagement Center | |
Charleston, South Carolina, United States, 29425 | |
United States, Texas | |
The Cooper Institute | |
Dallas, Texas, United States, 75230 | |
Baylor Endocrine Center | |
Dallas, Texas, United States, 75246 |
Principal Investigator: | Frank Greenway, MD | Pennington Biomedical Research Center |
Responsible Party: | Orexigen Therapeutics, Inc ( Ronald Landbloom, MD ) |
Study ID Numbers: | ZB 201 |
Study First Received: | June 18, 2006 |
Last Updated: | April 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00339014 |
Health Authority: | United States: Food and Drug Administration |
Body Weight Signs and Symptoms Obesity Dopamine Bupropion |
Zonisamide Nutrition Disorders Overweight Overnutrition |
Dopamine Uptake Inhibitors Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Antioxidants Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Psychotropic Drugs Protective Agents |
Pharmacologic Actions Therapeutic Uses Dopamine Agents Antidepressive Agents, Second-Generation Central Nervous System Agents Anticonvulsants Antidepressive Agents |