Clinical Trials/NCT00474630

NCT00474630

Completed

Phase 3

A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Naltrexone 32 mg Sustained Release (SR)/Bupropion 360 mg Sustained Release (SR) and Placebo in Obese Subjects With Type 2 Diabetes Mellitus

Orexigen Therapeutics, Inc53 sites in 1 country505 target enrollmentMay 2007

ConditionsObesity Overweight Diabetes Mellitus, Type 2

InterventionsPlacebo Naltrexone SR 32 mg/bupropion SR 360 mg/ day Ancillary therapy

DrugsNaltrexone SR 32 mg/bupropion SR 360 mg/ day Placebo

Overview

Phase: Phase 3
Intervention: Placebo
Conditions: Obesity
Sponsor: Orexigen Therapeutics, Inc
Enrollment: 505
Locations: 53
Primary Endpoint: Co-primary: Body Weight- Mean Percent Change
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is determine whether the combination of naltrexone SR and bupropion SR is safe and effective in treating obesity in subjects with type 2 diabetes.

Detailed Description

Optimal care of patients with diabetes mellitus includes vigorous and persistent efforts to achieve physiologic control of blood glucose as well as other often associated conditions including hypertension, dyslipidemia and excess weight. Pharmacologic interventions for the treatment of obesity in type 2 diabetes have shown significant reductions in HbA1c. 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 the combination of naltrexone SR and bupropion SR compared to placebo in obese subjects with type 2 diabetes mellitus.

Registry

clinicaltrials.gov

Start Date

May 2007

End Date

June 2009

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Orexigen Therapeutics, Inc

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female or male subjects aged 18 to 70 years of age (inclusive)
•Body mass index (BMI) ≥27 and ≤45 kg/m²
•Diagnosed with type 2 diabetes mellitus and on no injectable antidiabetes medication or inhaled insulin for more than 3 months prior to randomization
•Took stable doses of oral single or combination hypoglycemic medications (biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, sulfonylureas, DPP4 inhibitors) for at least 3 months prior to randomization or did not take medications for the treatment of type 2 diabetes mellitus
•Normotensive (systolic ≤145 mm Hg and diastolic ≤95 mm Hg). Antihypertensive medications were allowed with the exception of alpha-adrenergic blockers, and clonidine. Antihypertensive treatment was stable for at least 4 weeks prior to randomization.
•Medications for the treatment of dyslipidemia were allowed with the exception of cholestyramine and cholestypol as long as the medical regimen had been stable for at least 4 weeks prior to randomization.
•Free of opioid medication for 7 days prior to randomization
•HbA1c between 7% and 10%, fasting blood glucose \<270 mg/dL, and fasting triglycerides \<400 mg/dL
•No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), bilirubin, calcium, and phosphorus
•Creatinine levels were ≤1.4 mg/dL for female subjects and ≤1.5 mg/dL for male subjects

Exclusion Criteria

•Type I diabetes mellitus
•"Brittle-diabetes" or any hospitalization or emergency room visit due to poor diabetic control within 6 months prior to screening, history of diabetes-related dehydration leading to hospitalization, or history or evidence of ketoacidosis
•Obesity of known endocrine origin other than diabetes mellitus (e.g., untreated hypothyroidism, Cushing's syndrome, established polycystic ovary syndrome)
•Diabetes mellitus secondary to pancreatitis or pancreatectomy
•Serious medical condition including but not limited to renal or hepatic insufficiency and Class III or IV congestive heart failure; history of myocardial infarction, angina pectoris, claudication, or acute limb ischemia within 6 months prior to screening; lifetime history of stroke
•History of malignancy with exception of non-melanoma skin cancer or surgically cured cervical cancer within 5 years prior to screening
•Loss or gain of more than 5.0 kg within the 3 months prior to screening
•Severe microvascular or macrovascular complications of diabetes, including but not limited to proliferative retinopathy, active limb ulcerations, amputation of metatarsals or above
•Serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, and anorexia nervosa; current serious personality disorder (e.g., borderline or antisocial); current severe major depressive disorder; recent (6 months prior to screening) suicide attempt or current active suicidal ideation; or recent hospitalization due to psychiatric illness
•Response to the bipolar disorder questions that indicated the presence of bipolar disorder

Arms & Interventions

Placebo

Placebo with ancillary therapy

Intervention: Placebo

NB32

Naltrexone SR 32 mg/bupropion SR 360 mg/ day with ancillary therapy

Intervention: Naltrexone SR 32 mg/bupropion SR 360 mg/ day

NB32

Naltrexone SR 32 mg/bupropion SR 360 mg/ day with ancillary therapy

Intervention: Ancillary therapy

Placebo

Placebo with ancillary therapy

Intervention: Ancillary therapy

Outcomes

Primary Outcomes

Co-primary: Body Weight- Mean Percent Change

Time Frame: Baseline, 56 weeks

Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease

Time Frame: Baseline, 56 weeks

Secondary Outcomes

Change in Fasting Triglycerides Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in Fasting Blood Glucose Levels(Baseline, 56 weeks)
Change in Waist Circumference(Baseline, 56 weeks)
HbA1c- Proportion of Subjects With HbA1c <7% at Endpoint(Baseline, 56 weeks)
Percent of Subjects Requiring Rescue Medications for Diabetes(Baseline, 56 weeks)
Change in HbA1c Levels(Baseline, 56 weeks)
Change in Fasting HDL Cholesterol Levels(Baseline, 56 weeks)
Percent of Subjects With Dose Reduction in Oral Antidiabetes Medications(Baseline, 56 weeks)
HbA1c- Proportion of Subjects With HbA1c <6.5% at Endpoint(Baseline, 56 weeks)
Change in Fasting LDL Cholesterol Levels(Baseline, 56 weeks)
Change in Diastolic Blood Pressure(Baseline, 56 weeks)
Percent of Subjects With Dose Increase in Oral Antidiabetes Medications(Baseline, 56 weeks)
Change in HOMA-IR Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in IWQOL-Lite Total Scores(Baseline, 56 weeks)
Percent of Subjects Discontinuing Due to Poor Glycemic Control(Baseline, 56 weeks)
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire(Baseline, 56 weeks)
Body Weight- Proportion of Subjects With ≥10% Decrease(Baseline, 56 weeks)
Change in Fasting Insulin Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in Systolic Blood Pressure(Baseline, 56 weeks)
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data(Baseline, 56 weeks)
Change in IDS-SR Total Scores(Baseline, 56 weeks)
Change in Food Craving Inventory Sweets Subscale Score(Baseline, 56 weeks)
Change in Food Craving Inventory Carbohydrates Subscale Score(Baseline, 56 weeks)