A Phase IV Safety and Efficacy Study of VI-0521 in Adolescents With Obesity

Study Overview
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Brief Summary
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This study is being conducted to assess weight loss efficacy, as determined by changes in body mass index (BMI), and safety of VI-0521 (Qsymia®) or placebo, taken for 56 weeks accompanied by a lifestyle modification program in obese adolescents age 12-16 years.

Official Title
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A Phase IV, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study to Determine the Safety and Efficacy of VI-0521 in Obese Adolescents

Conditions
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Adolescent Obesity, Obesity in Adolescence, Adolescent Overweight

Intervention / Treatment
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* Drug: VI-0521 oral capsule
* Drug: Placebo oral capsule
* Behavioral: Lifestyle Modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 12 years and < 17 years; BMI ≥ the 95th percentile, with documented history of failure to lose sufficient weight or failure to maintain weight loss in a lifestyle modification program; If female, must be using adequate contraception, defined as double barrier methods, stable hormonal contraception plus single barrier method, tubal ligation, or abstinence. Exclusion Criteria: Type 1 diabetes; Congenital heart disease; clinically significant ECG abnormality; Clinically significant physical exam, vital signs, or laboratory abnormality; clinically significant hepatic or renal disease; Estimated Glomerular Filtration Rate (GFR; Schwartz formula) < 60 mL/minute; Clinically significant thyroid dysfunction as evidenced by signs, symptoms, or thyroid stimulating hormone (TSH) > 1.5 x Upper Limit of Normal; Obesity of known genetic or endocrine origin; History of bipolar disorder or psychosis, depression of moderate or greater severity, or presence or history of suicidal behavior or active suicidal ideation; Recent weight instability, or prior bariatric surgery; History of glaucoma or increased intraocular pressure; Current smoker or smoking cessation within 3 months of screening; Currently taking or plan on taking any of following medications during the study: Anticonvulsants used for treatment of seizure disorder, including barbiturates, benzodiazepines, gamma-aminobutyric acid (GABA) analogues, hydantoins, phenyltriazines, succinimides, and other agents (valproic acid and its derivatives, carbamazepine and its derivatives, zonisamide, and felbamate); Tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), lithium, levodopa, and dopamine receptor agonists; Carbonic anhydrase inhibitors; Insulin, Sulfonylureas (SFUs), glucagon-like peptide -1 (GLP-1) agonists, sodium glucose transporter-1 (SGLT-1), and SGLT-2 inhibitors; Chronic systemic steroids (i.e. glucocorticoids, anabolic steroids) other than oral contraceptives; Treatment for hyperactivity disorder; or Over the counter, prescription medications, herbal agents and dietary supplements used with the intention to lose body weight.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VI-0521 Mid Dose (Phentermine 7.5 mg +Topiramate 46 mg)<br>Weeks 1-2: VI-0521 (Phentermine 3.75 mg + Topiramate 23 mg) oral capsule, once daily; Weeks 3-56: VI-0521 (Phentermine 7.5 mg + Topiramate 46 mg) oral capsule, once daily | Drug: VI-0521 oral capsule<br>* Phentermine/Topiramate<br>* Other names: Phentermine and topiramate;Behavioral: Lifestyle Modification<br>* The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.<br>|
| Experimental: VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg)<br>Weeks 1-2: VI-0521 (Phentermine 3.75 mg + Topiramate 23 mg) oral capsule, once daily; Weeks 3-12: VI-0521 (Phentermine 7.5 mg + Topiramate 46 mg) oral capsule, once daily; Weeks 13-14: VI-0521 (Phentermine 11.25 mg + Topiramate 69 mg) oral capsule, once daily; Weeks 15-56: VI-0521 (Phentermine 15 mg + Topiramate 92 mg) oral capsule, once daily | Drug: VI-0521 oral capsule<br>* Phentermine/Topiramate<br>* Other names: Phentermine and topiramate;Behavioral: Lifestyle Modification<br>* The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.<br>|
| Placebo Comparator: Placebo<br>Subjects will receive placebo oral capsule, once daily for up to 56 weeks | Drug: Placebo oral capsule<br>* Inactive drug<br>Behavioral: Lifestyle Modification<br>* The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean % Change in Body Mass Index (BMI) | Mean % change in BMI from Baseline to Week 56 | Baseline to Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 |  | Baseline to Week 56 | 
| Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56 |  | Baseline to Week 56 | 
| Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56 |  | Baseline to Week 56 | 
| Change in Waist Circumference at Week 56 | Change in waist circumference from Baseline to Week 56 | Baseline, Week 56 | 
| Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56 | Mean changes in glycemic parameters [Whole Body Insulin Sensitivity Index (WBISI) (Matsuda)] from baseline to Week 56. The Oral Glucose Tolerance Test (OGTT) were performed at Baseline and Week 56 using 75 g oral glucose load; blood samples were obtained at baseline and at 2 hours post glucose load for evaluation of both glucose and insulin levels. Insulin Sensitivity was measured by obtaining glucose and insulin levels in a fasting state and at 2 hours after administration of oral glucose load. Matsuda index = 10,000/SQRT [glucose concentration (mg/dL) (fasting)*insulin concentration (uIU/mL) (fasting)*glucose concentration (mg/dL) (2 hours after glucose load)*insulin concentration (uIU/mL) (2 hours after glucose load)], with higher numbers indicating better insulin sensitivity. | Baseline, Week 56 | 
| Change in Fasting Insulin at Week 56 | Change in fasting insulin from Baseline to Week 56 | Baseline, Week 56 | 
| Percent Change in Triglycerides From Baseline to Week 56 |  | Baseline, Week 56 | 
| Percent Change in HDL-C From Baseline to Week 56 |  | Baseline, Week 56 | 
| Change From Baseline in Systolic Blood Pressure at Week 56 |  | Baseline, Week 56 | 
| Change From Baseline in Diastolic Blood Pressure at Week 56 |  | Baseline, Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight loss, obesity, weight control