A Study of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects Participating in a Behavior Modification Program

• Change in Body Weight [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]
• Percentage of Subjects Who Achieve a Weight Decrease of ≥5% [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]

• Effect on selected obesity-associated cardiovascular risk factors, including serum triglycerides, HDL and LDL cholesterol, waist circumference, glucose and insulin levels. [ Time Frame: Baseline to week 56 ] [ Designated as safety issue: No ]
• Percentage of Subjects Who Achieve a Weight Decrease of ≥10% [ Time Frame: Baseline, 56 weeks ] [ Designated as safety issue: No ]

• Proportion of subjects who lose at least 5% and 10% of their baseline body weight
• Effects on mood from baseline to week 56 as measured by the IDS-SR
• Effect on selected obesity-associated cardiovascular risk factors, including serum triglycerides, HDL and LDL cholesterol, waist circumference, glucose and insulin levels, HOMA-IR, hs-CRP levels and vital signs.
• Effects on quality of life from baseline to week 56 as measured by the IWQOL- Lite

The purpose of this study is to determine whether a combination of 2 drugs 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.

The combination of group lifestyle modification counseling and pharmacotherapy has recently been shown to result in nearly twice the average weight loss at one year (12.1 kg) as pharmacotherapy alone (sibutramine, 5.0 kg) or lifestyle modification counseling alone (6.7 kg). Combining pharmacotherapy with a comprehensive program of diet, exercise and group lifestyle modification counseling may provide the best weight loss regimen. This study will evaluate weight loss in subjects participating in such a comprehensive program who receive a combination of naltrexone SR and bupropion SR, or placebo.

• Drug: naltrexone SR/bupropionSR combination
  naltrexone SR 32 mg/bupropion SR 360 mg per day
• Behavioral: Intensive group lifestyle modification counseling
  Group lifestyle modification counseling
• Drug: PBO
  Other Name: placebo

• Experimental: NB32
  Naltrexone SR 32 mg/ bupropion SR 360 mg/ day with intensive group behavioral lifestyle modification counseling
  Interventions:

  • Drug: naltrexone SR/bupropionSR combination
  • Behavioral: Intensive group lifestyle modification counseling
• Placebo Comparator: PBO
  placebo with intensive group behavioral lifestyle modification counseling
  Interventions:

  • Behavioral: Intensive group lifestyle modification counseling
  • Drug: PBO

Inclusion Criteria:

• Female and male subjects, 18 to 65 years of age
• Have body mass index (BMI) between 30 and 45kg/m2 for subjects with uncomplicated obesity, and 27 and 45kg/m2 for subjects with obesity and controlled hypertension and/or dyslipidemia
• Non-smoker and no use of tobacco or nicotine products for at least 6 months
• Normotensive(< 140/90 mm Hg), some anti-hypertensive medications are allowed
• LDL cholesterol < 190 mg/dL and triglycerides < 400 mg/dL
• Women of child bearing potential must have negative serum pregnancy, must be non-lactating and agree to use effective contraception throughout the study period and 30 days after stopping study drug

Exclusion Criteria:

• Obesity of known endocrine origin such as untreated hypothyroidism or Polycystic Ovary Syndrome
• Serious medical condition
• Serious psychiatric illness
• Type I or Type II diabetes mellitus
• Need of medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months
• On prohibited concomitant medication
• History of surgical or device (e.g. lap band) intervention for obesity
• History of seizures or predisposition to seizures