Zonisamide SR Plus Bupropion SR Combination Therapy in Subjects With Obesity

Sponsor

Orexigen Therapeutics, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00709371

Collaborator

(none)

729

Enrollment

Locations

Arms

Duration (Months)

36.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is determine if the combination of zonisamide SR and bupropion SR are is more effective than either drug given alone or placebo in the treatment of obesity.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Zonisamide SR placebo/ bupropion SR placebo Drug: Zonisamide SR placebo/ bupropion SR 360 mg/day Drug: Zonisamide SR 120 mg/day/ bupropion SR placebo Drug: Zonisamide SR 360 mg/day/ bupropion SR placebo Drug: Zonisamide SR 120 mg/day/ bupropion SR 360 mg/day Drug: Zonisamide SR 360 mg/day/ bupropion SR 360 mg/day	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

729 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase IIB, Multi-Center, Dose-Parallel, Randomized, Double-Blind, Monotherapy and Placebo-Controlled Safety and Efficacy Study of Zonisamide SR Plus Bupropion SR Combination Therapy in Subjects With Obesity

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Combination tablet containing Zonisamide SR placebo plus bupropion SR placebo SR = Sustained Release	Drug: Zonisamide SR placebo/ bupropion SR placebo 2 placebo combination tablets twice daily for 16 weeks (maintenance period)
Active Comparator: Bupropion 360 Combination tablet containing Zonisamide SR placebo plus bupropion SR 360 mg/day; SR = Sustained Release	Drug: Zonisamide SR placebo/ bupropion SR 360 mg/day 2 placebo and bupropion SR 90 mg combination tablets, twice daily for 16 weeks (maintenance period)
Active Comparator: Zonisamide 120 Combination tablet containing Zonisamide SR 120 mg/day plus bupropion SR placebo; SR = Sustained Release	Drug: Zonisamide SR 120 mg/day/ bupropion SR placebo 2 zonisamide SR 30 mg and placebo combination tablets, twice daily for 16 weeks (maintenance period)
Active Comparator: Zonisamide 360 Combination tablet containing Zonisamide SR 360 mg/day plus bupropion SR placebo; SR = Sustained Release	Drug: Zonisamide SR 360 mg/day/ bupropion SR placebo 2 zonisamide SR 90 mg and placebo combination tablets, twice daily for 16 weeks (maintenance period)
Experimental: Zonisamide 120/Bupropion 360 Combination tablet containing Zonisamide SR 120 mg/day plus bupropion SR 360 mg/day; SR = Sustained Release	Drug: Zonisamide SR 120 mg/day/ bupropion SR 360 mg/day 2 zonisamide SR 30 mg and bupropion SR 90 mg combination tablets, twice daily for 16 weeks (maintenance period)
Experimental: Zonisamide 360/Bupropion 360 Combination tablet containing Zonisamide SR 360 mg/day plus bupropion SR 360 mg/day; SR = Sustained Release	Drug: Zonisamide SR 360 mg/day/ bupropion SR 360 mg/day 2 zonisamide SR 90 mg and bupropion SR 90 mg combination tablets, twice daily for 16 weeks (maintenance period)

Outcome Measures

Primary Outcome Measures

Percentage change in total body weight [from baseline to 24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Female or male subjects, 18 to 65 years of age
Have body mass index (BMI) ≥ 30 kg/m2 and ≤ 45 kg/m2 for subjects with uncomplicated obesity, and BMI of ≥ 27 kg/m2 and ≤ 45 kg/m2 for subjects with obesity and dyslipidemia and/or controlled hypertension
Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to screening
Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of adrenergic blockers and clonidine. Medical regimen must be stable for at least 6 weeks prior to randomization
Triglycerides <400 mg/dL. Medications for treatment of dyslipidemia are allowed with the exception of cholestyramine and cholestypol as long as medical regimen has been stable for at least 6 weeks prior to randomization
No clinically significant laboratory abnormalities
Negative urine drug screen
Negative serum pregnancy test in women of child-bearing potential
Women of child-bearing potential must be non-lactating, and agree to use acceptable contraception throughout the study period and for 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 or genetic origin (e.g., untreated hypothyroidism, Cushing's syndrome, polycystic ovary syndrome)
Serious medical condition
History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer.
History of suicide attempt or serious psychiatric illness
History of Major Depressive Disorder within the past 2 years
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
Type I or Type II diabetes
History of alcohol or drug abuse or dependence as determined by the Investigator within 1 year prior to randomization
History of surgical or device (e.g. gastric banding) intervention for obesity
History of seizures or predisposition to seizures
History of hypersensitivity to sulfonamides ("sulfa"), bupropion, or zonisamide
History of treatment with bupropion SR (Wellbutrin, Zyban) or zonisamide (Zonegran) within previous 12 months
History of nephrolithiasis (renal calculi)
Loss or gain of more than 4.0 kg within 3 months prior to randomization
Women of child bearing potential not adhering to a medically acceptable form of contraception
Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SelfCenter, PC	Fairhope	Alabama	United States	36532
2	Nutrition and Metabolic Research	La Jolla	California	United States	92037
3	Center for Human Nutrition/UCD	Denver	Colorado	United States	80220
4	Miami Research Associates	Miami	Florida	United States	33143
5	CSRA Partners in Health, Inc.	Augusta	Georgia	United States	30909
6	Radiant Research, Chicago	Chicago	Illinois	United States	60610
7	Welborn Clinic	Evansville	Indiana	United States	47713
8	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808
9	Nutrition and Weight Management Center, Boston Medical Center	Boston	Massachusetts	United States	02118
10	FutureCare Studies	Springfield	Massachusetts	United States	01103
11	Summit Research Network (Michigan), Inc.	Farmington Hills	Michigan	United States	48336
12	Mercy Health Research	St. Louis	Missouri	United States	63141
13	Center for Nutrition and Metabolic Disorders, University of Nevada School of Medicine	Reno	Nevada	United States	89557
14	Behavioral Medical Research	Staten Island	New York	United States	10305
15	Internal Medicine Associates of Charlotte	Charlotte	North Carolina	United States	28277
16	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
17	Summit Research Network (Oregon), Inc.	Portland	Oregon	United States	97210
18	The Cooper Institute	Dallas	Texas	United States	75230
19	Washington Center for Weight Management and Research	Arlington	Virginia	United States	22201
20	Summit Research Network (Seattle), LLC.	Seattle	Washington	United States	98104

Sponsors and Collaborators

Orexigen Therapeutics, Inc

Investigators

Principal Investigator: Matthew Acampora, MD, Internal Medicine Associates of Charlotte
Principal Investigator: Caroline Apovian, MD, Nutrition and Weight Management Center
Principal Investigator: James Bergthold, MD, Summit Research Network (Oregon), Inc.
Principal Investigator: Joseph Cleaver, MD, The Cooper Institute
Principal Investigator: Adnan Dahdul, MD, FutureCare Studies
Principal Investigator: Ken Fujioka, MD, Nutrition and Metabolic Research
Principal Investigator: Jeffrey Geohas, MD, Radiant Research, Chicago
Principal Investigator: Mark Graves, MD, Welborn Clinic
Principal Investigator: Alok Gupta, MD, Pennington Biomedical Research Center
Principal Investigator: Wayne Harper, MD, Wake Research Associates, LLC
Principal Investigator: Jonathan Henry, MD, Summit Research Network (Michigan), Inc.
Principal Investigator: Diane Krieger, MD, Miami Research Associates
Principal Investigator: Michael Levy, MD, Behavioral Medical Research
Principal Investigator: Raymond Plodkowski, MD, Center for Nutrition and Metabolic Disorders, University of Nevada School of Medicine
Principal Investigator: Domenica Rubino, MD, Washington Center for Weight Management and Research
Principal Investigator: Stan Self, MD, SelfCenter, PC
Principal Investigator: Diane Smith, MD, CSRA Partners in Health, Inc.
Principal Investigator: Timothy Smith, MD, Mercy Research
Principal Investigator: Claire Waltman, MD, Summit Research Network (Seattle), LLC
Principal Investigator: Holly Wyatt, MD, Center for Human Nutrition/UCD