Method-of-Use Study Assessing the Effect of Naltrexone Sustained Release (SR)/ Bupropion SR on Body Weight and Cardiovascular Risk Factors in Overweight and Obese Subjects

Study Overview
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Brief Summary
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The purpose of this Phase 3b study is to assess the effects of combination therapy with naltrexone SR/bupropion SR (NB) used in conjunction with a comprehensive lifestyle intervention (CLI) and in a manner consistent with its intended use after marketing approval, on body weight and cardiovascular risk factors compared to the effects of Usual Care in subjects who are overweight with dyslipidemia and/or controlled hypertension or obese. Subjects in the NB and CLI group are required to undergo an evaluation to continue treatment at Week 16. Subjects are to be discontinued from full participation if they do not lose at least 5% of their body weight relative to baseline and/or are experiencing sustained increases in blood pressure (systolic or diastolic) of ≥10 mmHg above baseline. At Week 26, subjects originally assigned to Usual Care switch to treatment with NB and CLI, and subjects assigned to NB and CLI continue treatment for the duration of the study (78-weeks treatment period).

Official Title
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A Multicenter, Randomized, Open-Label, Controlled, Method-of-Use Study Assessing the Effect of Naltrexone Sustained Release (SR)/Bupropion SR on Body Weight and Cardiovascular Risk Factors in Overweight and Obese Subjects (The Ignite Study)

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: NB
* Behavioral: CLI
* Behavioral: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male, 18 to 60 years old Body mass index (BMI) ≥30 kg/m2 and ≤45 kg/m2 for subjects with uncomplicated obesity, or BMI ≥27 kg/m2 and ≤45 kg/m2 for subjects with dyslipidemia and/or controlled hypertension Exclusion Criteria: History of type 1 or type 2 diabetes mellitus diagnosis Myocardial infarction within 6 months prior to screening Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading scheme Clinical history of large vessel cortical strokes, including ischemic and hemorrhagic strokes (i.e., transient ischemic attack is not exclusionary) History (within the last 20 years) of seizures, cranial trauma, bulimia, anorexia nervosa, or other conditions that predispose subjects to seizures Past or planned surgical or device intervention (e.g., gastric banding) for obesity Chronic use or positive screen for opioids Regular use of tobacco products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NB + CLI<br>Naltrexone SR 32 mg/Bupropion SR 360 mg/day (NB) with comprehensive lifestyle intervention (CLI) | Drug: NB<br>* Naltrexone SR 32 mg/Bupropion SR 360 mg (NB) in combination tablets (daily dosage)<br>Behavioral: CLI<br>* The Comprehensive Lifestyle Intervention (CLI) program includes telephone counseling, internet education, goal setting, and online tracking tools.<br>|
| Other: Usual Care<br>Usual Care (self-directed lifestyle intervention) Usual Care: Usual Care was a self-directed lifestyle intervention in which subjects were given calorie targets, instructions to increase exercise, and a pamphlet about weight loss by study site staff. | Behavioral: Usual Care<br>* Usual Care is a self-directed lifestyle intervention program<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Body Weight From Baseline (Day 1) to Week 26 |  | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a Loss of at Least 5% of Baseline Body Weight at Week 26 |  | Baseline to Week 26 | 
| Percentage of Subjects Achieving a Loss of at Least 10% of Baseline Body Weight at Week 26 |  | Baseline to Week 26 | 
| Percentage of Subjects Achieving a Loss of at Least 15% of Baseline Body Weight at Week 26 |  | Baseline to Week 26 | 
| Absolute Change in Body Weight From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Waist Circumference From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Fasting Triglycerides From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Fasting Low-density Lipoprotein Cholesterol From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Fasting High-density Lipoprotein Cholesterol From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Systolic Blood Pressure From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Diastolic Blood Pressure From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Heart Rate From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Fasting Plasma Glucose From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change Fasting Insulin From Baseline to Week 26 |  | Baseline to Week 26 | 
| Change in Homeostasis Model Assessment-insulin Resistance (HOMA-IR) From Baseline to Week 26 | HOMA-IR is an insulin sensitivity index that is calculated as HOMA-IR = (Glucose * Insulin) / 405, where glucose is in mass units (mg/dL) and insulin is in µIU/mL. Higher values indicate lower insulin sensitivity. | Baseline to Week 26 | 
| Change in Patient-reported Binge Eating Scale (BES) Total Scores From Baseline to Week 26 | The BES is a 16-item questionnaire that identifies different levels of binge-eating severity, with total scores ranging between 0-46. BES scores were categorized as follows: None = Scores ≤17 indicated no significant binge eating, Moderate = scores from 18 to 26 (inclusive), Severe = scores ≥27 indicated severe levels of binge eating. | Baseline to Week 26 | 
| Change in Patient-reported Arizona Sexual Experiences Scale (ASEX) Total Scores From Baseline to Week 26 | Arizona Sexual Experiences (ASEX) scale is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. | Baseline to Week 26 | 
| Change in Patient-reported Impact of Weight on Quality of Life-Lite Questionnaire (IWQOL-Lite) Total Score From Baseline to Week 26 | Impact of Weight on Quality of Life-Lite Questionnaire (IWQOL-Lite) is a self-reported assessment of perceived effect of weight on quality of life. It consists of 31 items organized in 5 domains (physical function, self-esteem, sexual life, public distress and work). IWQOL-Lite 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 to Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, overweight