A Study of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects

Inclusion Criteria:

• Female and male subjects, 18 to 65 years of age
• Have body mass index (BMI) of 30 to 45 kg/m2 for subjects with uncomplicated obesity, and BMI of 27 to 45 kg/m2 for subjects with obesity and controlled hypertension and/or dyslipidemia
• Normotensive (systolic BP < or = 140 mm Hg; diastolic < or = 90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine. Medical regimen must be stable for at least 6 weeks prior to randomization
• Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks prior to randomization
• Free of opioid medication for 7 days prior to randomization
• No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal
• No clinically significant abnormality of hematocrit, white blood cell count, white cell differential, or platelets
• Fasting glucose < 126 mg/dL on no hypoglycemic agents, fasting triglycerides < 400 mg/dL
• No clinically significant abnormality on urinalysis
• Thyroid stimulating hormone (TSH) within normal limits or normal T3, if TSH is below normal limits
• Negative serum pregnancy test in women of child bearing potential
• Negative urine drug screen
• Inventory of Depressive Symptoms-Subject Rated(IDS-SR) scores <2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality) and IDS-SR total score <30
• If woman of child bearing potential, must be non-lactating and agree to use effective contraception throughout the study period and 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 if unknown endocrine origin
• Serious medical condition
• History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer
• A lifetime history a serious psychiatric illness
• Current serious psychiatric illness
• A response to bipolar disorder questions indicating presence of bipolar disorder
• 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
• History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study participation
• Type 1 or Type 2 diabetes mellitus
• Screening ECG with QTcB >450 msec (men) or >470 msec (women) or the presence of any clinically significant cardiac abnormalities
• On prohibited concomitant medications
• History of surgical or device (e.g. gastric banding) intervention for obesity
• History of seizures of any etiology, or of predisposition to seizures
• History of treatment with bupropion, or naltrexone within the preceding 12 months
• History of hypersensitivity or intolerance to bupropion or naltrexone
• Initiation or discontinuation of tobacco products; Use of nicotine replacement products (nicotine gum, patch etc) during this period is excluded
• Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization
• Loss or gain of more than 4.0 kilograms within 3 months prior to randomization
• Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug
• Use of investigational drug, device or procedure in the previous 30 days
• Participation in any previous clinical trial sponsored by Orexigen Therapeutics
• Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study
• Investigators, study personnel, sponsor representatives and their immediate families