A Safety and Efficacy Study Comparing Naltrexone SR/Bupropion SR and Placebo in Obese Subjects With Type 2 Diabetes

Inclusion Criteria

• Female or male subjects aged 18 to 70 years of age (inclusive)
• Body mass index (BMI) ≥27 and ≤45 kg/m²
• Diagnosed with type 2 diabetes mellitus and on no injectable antidiabetes medication or inhaled insulin for more than 3 months prior to randomization
• Took stable doses of oral single or combination hypoglycemic medications (biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, sulfonylureas, DPP4 inhibitors) for at least 3 months prior to randomization or did not take medications for the treatment of type 2 diabetes mellitus
• Normotensive (systolic ≤145 mm Hg and diastolic ≤95 mm Hg). Antihypertensive medications were allowed with the exception of alpha-adrenergic blockers, and clonidine. Antihypertensive treatment was stable for at least 4 weeks prior to randomization.
• Medications for the treatment of dyslipidemia were allowed with the exception of cholestyramine and cholestypol as long as the medical regimen had been stable for at least 4 weeks prior to randomization.
• Free of opioid medication for 7 days prior to randomization
• HbA1c between 7% and 10%, fasting blood glucose 450 msec (men) and >470 msec (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with recent myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities
• Received the following excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents, and agents for the treatment of attention deficit disorder) with the exception of low-dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over-the-counter dietary supplements or herbs with psychoactive, appetite, or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine, cholestypol, Depo Provera®; smoking cessation agents; use of opioid or opioid-like medications, including analgesics and antitussives
• History of surgical or device intervention for obesity (e.g., gastric banding)
• History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures)
• Treatment with bupropion or naltrexone within 12 months prior to screening
• History of hypersensitivity or intolerance to bupropion or naltrexone
• Changes in smoking status or in tobacco or nicotine use within 3 months prior to screening or planned during study participation
• Participated in a weight loss management program within one month prior to randomization
• Females who were pregnant or breast-feeding or planned to become pregnant during the study period or within 30 days of discontinuing study drug
• Planned surgical procedure that could impact the conduct of the study
• Received any investigational drug or used an experimental device or procedure within the previous 30 days
• Participated in any previous clinical trial conducted by Orexigen
• Had any condition that in the opinion of the investigator made the subject unsuitable for inclusion into the study