A Safety and Efficacy Study of Naltrexone SR/Bupropion SR in Obesity

Official Title: “A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Naltrexone Sustained Release (SR)/Bupropion Sustained Release (SR) and Placebo in Obese Subjects”

The purpose of this study is to determine if a combination of two drugs leads to more weight loss than each drug alone.

Two Phase II clinical trials have demonstrated that the combination of naltrexone and bupropion SR is associated with greater weight loss than naltrexone alone, bupropion SR alone or placebo in subjects with uncomplicated obesity. The current study will investigate the safety and efficacy of the combination compared to placebo in obese subjects with uncomplicated obesity and in those with obesity and hypertension and/or dyslipidemia.

Intervention(s) in this Clinical Trial

• Drug: naltrexone SR/bupropion SR
  • naltrexone SR 32 mg/bupropion SR 360 mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • naltrexone SR/bupropion SR
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Co-primary outcome measures are the percentage of total body weight lost and the percentage of subjects who achieve a weight decrease of greater than or equal to 5%
  • Time Frame: 56 weeks
    Safety Issue?: No

Secondary Measures

• Proportion of subjects achieving a weight loss of ≥10%; Waist circumference; Fasting triglyceride,insulin, blood glucose and HDL cholesterol; HOMA-IR:IW QOL-Lite score; SF-36; IDS-SR score; hs-CRP; systolic and diastolic blood pressure
  • Time Frame: 56 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Female and male subjects, 18 to 65 years of age
• Have BMI of 30 to 45kg/m2 for subjects with uncomplicated obesity, and BMI of 27 to 45kg/m2 for subjects with obesity and controlled hypertension and/or dyslipidemia
• Normotensive (systolic < or = to 140 mm Hg; diastolic < or = 90 mm Hg).
• Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers, and clonidine. Medical regimen must be stable for at least 6 weeks prior to randomization
• Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks prior to randomization
• Free of any opioid medication for at least 7 days prior to randomization
• No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus
• ALT and AST within 2.5 x upper limit of normal (ULN)
• No clinically significant abnormality of hematocrit, white blood cell count, white cell differential, or platelets
• Fasting glucose < 126 mg/dL on no hypoglycemic agents, fasting triglycerides < 400 mg/dL.
• TSH within normal limits or normal T3, if TSH is below normal limits
• Negative serum pregnancy test in women of child bearing potential
• Negative urine drug screen
• If woman of child bearing potential, must be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug
• Able to speak and read English

Exclusion Criteria:

• Serious medical condition
• History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer
• A lifetime history a serious psychiatric illness
• Current serious psychiatric illness
• In need of 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 participation.
• Type I or Type II diabetes mellitus
• On prohibited concomitant medications
• History of surgical or device (e.g. gastric banding) intervention for obesity
• History of seizures of any etiology, or of predisposition to seizures
• History of treatment with bupropion, or naltrexone within the preceding 12 months
• History of hypersensitivity or intolerance to bupropion or naltrexone
• Use of nicotine replacement products (nicotine gum, patch etc) during study participation is not allowed.
• Loss or gain of more than 4.0 kilograms within 3 months prior to randomization
• Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Orexigen Therapeutics, Inc Industry

Overall Clinical Trial Officials and Contacts

Frank Greenway, MD Principal Investigator Pennington Medical Research Center, Louisiana State University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00567255

Study ID Number: NB-303

ClinicalTrials.gov Identifier: NCT00567255

Health Authority: United States: Food and Drug Administration