Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Female and male subjects, 18 to 60 years of age
Have body mass index (BMI) of 30 to 40 kg/m2
Free from 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 baseline
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
No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, calcium and phosphorus
Bilirubin, ALT and AST within 1.5 x ULN
No clinically significant abnormality of hematocrit, white blood cell count, white cell differential, or platelets
Fasting glucose less than 140 mg/dL on no hypoglycemic agents
No clinically significant abnormality on urinalysis
TSH within 1.5 x ULN, normal T3, if TSH below lower limit of normal
Negative serum pregnancy test in women with intact uterus
Score < 11 for depression and score < 11 for anxiety on Hospital Anxiety and Depression (HAD) Scale
ECG: no clinically significant abnormality
Score of zero on the Mood Assessment questionnaire and a response of "No" to the Bipolar Disorder Questions
If female with child-bearing potential, must be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drugs
Able to comply with all required study procedures and schedule
Willing and able to give written informed consent

Exclusion Criteria:

Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome)
Serious medical condition or medical condition that limits participation in the prescribed exercise program: (e.g. unstable cardiovascular disease including congestive heart failure, angina pectoris, and myocardial infarction; stroke; claudication; acute limb ischemia; acute renal or hepatic disorder; renal, hepatic or respiratory insufficiency)
Active malignancy or history of malignancy (other than non-melanoma skin cancer or surgically cured cervical cancer) within 5 years of enrollment
Serious psychiatric condition (e.g., any history of bipolar disorder, psychosis, suicidal attempt or post-partum depression; a history of major depression, suicidal ideation or antidepressant use within 1 year)
Type I or Type II diabetes mellitus requiring pharmacotherapy
Excluded concomitant medications: anorectic agents; weight loss agents; dietary supplements to promote muscle building, enhance mood, or reduce appetite; adrenergic blockers; beta blockers; anti-psychotic agents; clonidine; theophylline; cimetidine; oral corticosteroids; anti-depressant; topiramate; Depo-Provera®, smoking cessation agents; frequent, known use of opioid or opioid-like analgesics
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 febrile seizures)
History of bulimia or anorexia nervosa
History of drug or alcohol abuse within 5 years
History of treatment with bupropion, or naltrexone within 12 months
History of hypersensitivity to bupropion, or naltrexone
Use of drugs, herbs, or dietary supplements known to significantly affect body weight within one month of baseline
Use of investigational drug, device or procedure within 90 days
Participation in any previous clinical trial conducted by Orexigen Therapeutics
Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study