A Safety and Efficacy Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in an Intensive Behavior Modification Program
Condition: Obesity; Overweight
MeSH terms: Obesity; Overweight
Intervention: Naltrexone SR 32 mg/ bupropion SR 360 mg/ day; Placebo; Intensive group lifestyle modification counseling
Intervention MeSH terms: Naltrexone; Bupropion
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 793.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Obesity; Behavior Modification

Summary:

      The purpose of this study is to determine whether a combination of naltrexone SR and
      bupropion SR is safe and effective in treating obesity and leads to greater weight loss when
      given with a group lifestyle modification program than with group lifestyle modification
      alone.
    

Eligibility 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 controlled
             hypertension and/or dyslipidemia

          -  Non-smoker and had not used tobacco or nicotine products for at least 6 months before
             screening

          -  Normotensive (systolic ≤140 mm Hg and diastolic ≤90 mm Hg). Anti-hypertensive
             medications were allowed with the exception of alpha-adrenergic blockers,
             beta-blockers, and clonidine. Medical regimen was to be stable for at least 8 weeks.

          -  Low-density lipoprotein level <190 mg/dL and triglycerides level <400 mg/dL.
             Medications for the treatment of dyslipidemia were allowed as long as the medical
             regimen had been stable for at least 8 weeks.

          -  No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN),
             creatinine, bilirubin, calcium and 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

          -  No clinically significant abnormality on urinalysis

          -  Thyroid stimulating hormone (TSH) within 1.5 times ULN or normal triiodothyronine
             (T3), if TSH was below normal limits

          -  Female subjects of childbearing potential had a negative serum pregnancy test

          -  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

          -  Completed a food diary for 6 of 7 consecutive days during screening

          -  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,
             established polycystic ovary syndrome)

          -  Serious medical condition (including but not limited to renal or hepatic
             insufficiency; congestive heart failure, angina pectoris, myocardial infarction,
             stroke, claudication, or acute limb ischemia; history of malignancy with exception of
             non-melanoma skin cancer or surgically cured cervical cancer)

          -  Serious psychiatric illness (e.g., lifetime history of bipolar disorder, schizophrenia
             or other psychosis, bulimia, and anorexia nervosa; current serious personality
             disorder, e.g., borderline; severe major depressive disorder, recent [previous 6
             months] suicide attempt or current active suicidal ideation, 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

          -  History of drug or alcohol abuse or dependence within 1 year

          -  Type I or Type II diabetes mellitus

          -  Baseline 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)
             with the exception of low-dose benzodiazepine or hypnotic agents for the treatment of
             insomnia; any anorectic or weight loss agents; any over-the-counter dietary
             supplements with psychoactive, appetite or weight effects; alpha-adrenergic blockers;
             beta-blockers; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids;
             topiramate, Depo-Provera®; smoking cessation agents; regular use of opioid or
             opioid-like analgesics

          -  History of surgical or device (e.g., lap band) 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

          -  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 baseline

          -  Loss or gained >4.0 kilograms within the previous 3 months

          -  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