A Study of the Safety and Efficacy of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects

Obesity Clinical Trial

Official title:

A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Two Doses of Naltrexone Sustained Release (SR)/Bupropion Sustained Release (SR) and Placebo in Obese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00532779
• Other study ID #: NB-301
• Secondary ID: COR-I
• Status: Completed
• Phase: Phase 3
• First received: September 19, 2007
• Last updated: November 18, 2014
• Start date: October 2007
• Est. completion date: May 2009

Study information

• Verified date: November 2014
• Source: Orexigen Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether 2 doses of the combination of naltrexone SR and bupropion SR are safe and effective in the treatment of obesity.

Description:

Two Phase II clinical trials demonstrated that a combination of bupropion SR and naltrexone is associated with greater weight loss than bupropion SR alone, naltrexone alone, or placebo in subjects with uncomplicated obesity. The current study investigated the safety and efficacy of 2 doses of the combination of naltrexone SR and bupropion SR compared to placebo in obese subjects with uncomplicated obesity and in those with overweight/obesity and hypertension and/or dyslipidemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1742
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Female and male subjects, 18 to 65 years of age;

• Have BMI =30 and =45kg/m² for subjects with uncomplicated obesity, and BMI of =27 and =45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia;

• Normotensive (systolic =140 mm Hg; diastolic =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 opioid medication for 7 days prior to randomization;

• No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus;

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

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

• Fasting glucose < 126 mg/dL on no hypoglycemic agents, fasting triglycerides <400 mg/dL;

• No clinically significant abnormality on urinalysis;

• 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;

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

• Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;

• Able to comply with all required study procedures and schedule;

• Able to speak and read English;

• Willing and able to give written informed consent.

Exclusion Criteria:

• Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome);

• Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, 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;

• A 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;

• A response to bipolar disorder questions indicating the presence of bipolar disorder;

• 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 initiation;

• Type 1 or Type 2 diabetes mellitus;

• Screening ECG with a corrected QT interval by the method of Bazett (QTcB) >450 msec (men) and > 470 millisecond (msec) (women) 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;

• Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, 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 medications, 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 (such as cigarettes, cigars, pipes, etc), chewing tobacco or snuff in the 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (nicotine gum, patch) during study participation was not allowed;

• Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization;

• 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;

• Planned surgical procedure that can impact the conduct of the study;

• Use of investigational drug, device or procedure within the previous 30 days;

• Participation in any previous clinical trial sponsored by Orexigen Therapeutics;

• Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study;

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• Naltrexone SR 16 mg/Bupropion SR 360 mg /day

• Naltrexone SR 32 mg/Bupropion SR 360 mg /day

• Placebo

Behavioral:
• Ancillary therapy
Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

Locations

Country	Name	City	State
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Georgia Clinical Research	Atlanta	Georgia
United States	CSRA Partners in Health, Inc	Augusta	Georgia
United States	Covance Clinical Research Unit Austin	Austin	Texas
United States	Health Trends Research, LLC	Baltimore	Maryland
United States	Pennington Biomedical Research Center	Baton Rouge	Louisiana
United States	Radiant Research	Birmingham	Alabama
United States	Radiant Research, Phoenix Southeast	Chandler	Arizona
United States	Center for Nutrition and Preventive Medicine	Charlotte	North Carolina
United States	Radiant Research	Chicago	Illinois
United States	Rapid Medical Research, Inc.	Cleveland	Ohio
United States	Central Ohio Nutrition Center, Inc.	Columbus	Ohio
United States	Internal Medicine Associates of Cordova	Cordova	Tennessee
United States	Baylor Endocrine Center	Dallas	Texas
United States	Radiant Research	Dallas	Texas
United States	Welborn Clinic	Evansville	Indiana
United States	SelfCenter, PC	Fairhope	Alabama
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Jackson Clinic, PA	Jackson	Tennessee
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	Miami Research Associates	Miami	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Advance Clinical Research Institute	Orange	California
United States	Radiant Research Kansas City	Overland Park	Kansas
United States	University Clinical Research	Pembroke Pines	Florida
United States	Summit Research Network (Oregon), Inc.	Portland	Oregon
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	Center for Nutrition and Metabolic Disorders	Reno	Nevada
United States	Oakwell Clinical Research	San Antonio	Texas
United States	Radiant Research	San Antonio	Texas
United States	Scripps Clinic Del Mar	San Diego	California
United States	VA San Diego Healthcare System	San Diego	California
United States	Medical Research Institute	Slidell	Louisiana
United States	FutureCare Studies	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Orexigen Therapeutics, Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, plac — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Co-primary: Body Weight- Mean Percent Change		Baseline, 56 weeks	No
Primary	Co-primary: Body Weight- Proportion of Subjects With =5% Decrease		Baseline, 56 weeks	No
Secondary	Body Weight- Proportion of Subjects With =10% Decrease		Baseline, 56 weeks	No
Secondary	Change in Waist Circumference		Baseline, 56 weeks	No
Secondary	Change in Fasting HDL Cholesterol Levels		Baseline, 56 weeks	No
Secondary	Change in Fasting Triglycerides Levels, Using Log-transformed Data		Baseline, 56 weeks	No
Secondary	Change in IWQOL-Lite Total Scores	IWQOL-Lite= Impact of Weight on Quality of Life-Lite Questionnaire Total score is based on a scale from 0 to 100, with 0 representing the poorest and 100 the best quality of life and where a score of 71-79 indicates moderate impairment	Baseline, 56 weeks	No
Secondary	Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data		Baseline, 56 weeks	No
Secondary	Change in Fasting Insulin Levels, Using Log-transformed Data		Baseline, 56 weeks	No
Secondary	Change in Fasting Blood Glucose Levels		Baseline, 56 weeks	No
Secondary	Change in HOMA-IR Levels, Using Log-transformed Data	HOMA-IR= Homeostasis Model Assessment-Insulin Resistance	Baseline, 56 weeks	No
Secondary	Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire	Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult	Baseline, 56 weeks	No
Secondary	Change in Fasting LDL Cholesterol Levels		Baseline, 56 weeks	No
Secondary	Change in Systolic Blood Pressure		Baseline, 56 weeks	No
Secondary	Change in Diastolic Blood Pressure		Baseline, 56 weeks	No
Secondary	Change in IDS-SR Total Scores	IDS-SR= Inventory of Depressive Symptoms-Subject Rated IDS-SR total score is based on 30 items. The total score can range from 0-84, with 0 being no depressive symptoms and 84 being very severe depressive symptoms. A total score = 13 indicates no depression.	Baseline, 56 weeks	Yes
Secondary	Change in Food Craving Inventory Sweets Subscale Score	The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The sweets subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).	Baseline, 56 weeks	No
Secondary	Change in Food Craving Inventory Carbohydrates Subscale Score	The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The carbohydrates subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).	Baseline, 56 weeks	No