Safety and Efficacy of Different Combinations of Zonisamide-CR Plus Bupropion-SR to Treat Uncomplicated Obesity

Inclusion Criteria: * Have body mass index (BMI) of 30 to 43 kg/m2 * Free from any other 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 screening * 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 * Negative serum pregnancy test in women with an intact uterus * Score \< 15 for depression and score \< 15 for anxiety on Hospital Anxiety and Depression Scale (HADS) * No clinically significant abnormality on ECG * Not on eExcluded concomitant medications * If female with intact uterus, be non-lactating, and agree to use effective contraception throughout the study period and for 30 days after discontinuation of study drugs. * Able to comply with all required study procedures and schedule * Able to use and have access to a touch tone telephone and to speak and read English Exclusion Criteria: * Obesity of known endocrine or genetic origin * Serious medical condition * Serious psychiatric illness * Active suicidal ideation; score \> 2 on the Mood Assessment questionnaire * A response to Bipolar Disorder questions indicating the presence of Bipolar Disorder * Type I diabetes mellitus or Type II diabetes mellitus requiring pharmacotherapy * History of alcohol or drug abuse, current or within 5 years * History of bulimia or anorexia nervosa * 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 alcohol withdrawal or febrile seizures) * History of hypersensitivity to sulfonamides ("sulfa"), bupropion, or zonisamide * History of nephrolithiasis (renal calculi) * History of treatment with bupropion SR (Wellbutrin, Zyban) or zonisamide (Zonegran) within 12 months * Use of drugs, herbs, or dietary supplements known to significantly affect body weight or participation in a weight loss management program within one month prior to baseline * Loss or gain of more than 4.0 kilos within 3 months * Women of child bearing potential not adhering to an acceptable form of contraception * Pregnant or breast-feeding women * Use of investigational drug, device or procedure within 30 days * Participation in any previous clinical trial conducted by Orexigen Therapeutics * Planned surgical procedure that can impact the conduct of the study * Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study