A Safety and Efficacy Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects

• Status: Completed
• Trial end date: 2009-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether the combination of naltrexone SR and bupropion SR is safe and effective in the treatment of obesity.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Orexigen Therapeutics, Inc
• Treatments: Bupropion; Naltrexone

Criteria

Inclusion Criteria:

• Female or male subjects aged 18 to 65 years (inclusive)

• Body mass index (weight [kg]/height [m²]) ≥30 and ≤45 kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45 kg/m² for subjects with obesity with controlled hypertension and/or dyslipidemia

• Normotensive (systolic ≤140 mm Hg and diastolic ≤90 mm Hg). Anti-hypertensive medications were allowed with the exception of alpha-adrenergic blockers and clonidine. Medical regimen was to be stable for at least 6 weeks prior to randomization.

• Medications for the treatment of dyslipidemia were allowed as long as the medical regimen had 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 (BUN), creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 times upper limit of normal (ULN)

• No clinically significant abnormality of hematocrit, white blood cell (WBC) count, WBC differential, or platelets

• Fasting glucose <126 mg/dL and not receiving hypoglycemic agents and fasting triglycerides level <400 mg/dL

• No clinically significant abnormality on urinalysis

• Thyroid stimulating hormone (TSH) within normal limits or normal triiodothyronine (T3), if TSH was below normal limits

• Female subjects of childbearing potential had a negative serum pregnancy test

• Negative urine drug screen (UDS)

• An IDS-SR score <2 on individual items: 5 (sadness), 6 (irritability), 7 (anxiety/tension), and 18 (suicidality) and an IDS-SR total score <30

• Female subjects of childbearing potential were non-lactating and agreed to continue to use effective contraception throughout the study and 30 days after discontinuation of study drug

• Able to comply with all required study procedures and schedule

• Able to speak and read English

• Provided written informed consent

Exclusion Criteria:

• Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome)

• Serious medical condition (including but not limited to renal or hepatic insufficiency; Class III or IV congestive heart failure, history of angina pectoris, myocardial infarction, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke)

• History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer

• Lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa

• Current serious psychiatric illness including severe personality disorder (e.g., borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation or recent hospitalization due to psychiatric illness

• Response to the bipolar disorder questions that indicated the presence of bipolar disorder

• Required 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 initiation

• Type I or Type II diabetes mellitus

• Screening ECG with a corrected QT (QTc) interval (using Bazett's formula >450 millisecond (msec) [males] and >470 msec [females]) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities

• Received excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer or anticonvulsant agents or 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 analgesics, including analgesics and antitussives

• History of surgical or device (e.g., gastric banding) intervention for obesity

• 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)

• 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 including inhaled tobacco (e.g., cigarettes, cigars, pipes, etc), chewing tobacco or snuff within 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (e.g., nicotine gum, patch, etc) during study participation was not allowed

• Used drugs, herbs, or dietary supplements believed to significantly affect body weight or participated in a weight loss management program within one month prior to randomization

• Loss or gained >4.0 kilograms within the previous 3 months prior to randomization

• Females who were pregnant or breast-feeding or planning 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

• Investigators, study personnel, sponsor representatives and their immediate families