A Pharmacokinetic Study Comparing VI-0521 With Placebo in Obese Adolescents

Study Overview
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Brief Summary
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The primary objective of this study is to describe the pharmacokinetic profiles of VI-0521 in obese adolescents.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Pharmacokinetic and Pharmacodynamic Study of VI-0521 in Obese Adolescents

Conditions
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Pediatric Obesity, Childhood Obesity

Intervention / Treatment
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* Drug: Placebo
* Drug: VI-0521 Mid Dose
* Drug: VI-0521 Top Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent; Provide written assent (of study subject); Adolescent ≥12 and <18 years of age; Have a BMI ≥ the 95th percentile of BMI for age and gender; Female subjects must be using adequate contraception; Willing and able to comply with all study requirements Exclusion Criteria: Condition or disease interfering with metabolism; Any medical treatment with insulin; Hyperthyroidism, or clinically significant hypothyroidism; Any history of bipolar disorder or psychosis, major depressive disorder, or history of suicidal behavior or ideation, or any use of antidepressant medications; Use of chronic systemic glucocorticoid or steroid therapy; History of any eating disorders; Any history of laxative abuse; Prior bariatric surgery; Any history of nephrolithiasis; Any history of epilepsy, or treatment with anti-seizure medications; Positive urine drug screen; Current smoker or smoking cessation within the previous 3 months of screening; Obesity of a known genetic or endocrine origin; Treatment with any over-the-counter or prescription weight loss drug, or attention-deficit/hyperactivity disorder (ADHD); Allergy or hypersensitivity to phentermine or topiramate or history of anaphylaxis to any drug; Use of any investigational medication or device for any indication or participation in a clinical study within 30 days prior to screening; or Any medical or surgical condition which would impair the ability of the subject to complete the study, compromise the quality of study data, or pose an unacceptable risk to the safety of the subject.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Days 1-56: Placebo | Drug: Placebo<br>* po once daily<br>* Other names: Sugar Pill;|
| Experimental: VI-0521 Mid Dose<br>Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | Drug: VI-0521 Mid Dose<br>* po once daily<br>* Other names: Phentermine/Topiramate;|
| Experimental: VI-0521 Top Dose<br>Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-28: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) Days 29-42: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg) Days 43-56: VI-0521 (Phentermine/Topiramate 15 mg/92 mg) | Drug: VI-0521 Top Dose<br>* po once daily<br>* Other names: Phentermine/Topiramate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent Clearance (CL/F) of Phentermine and Topiramate | A Bayesian analysis was performed to derive posterior Bayes individual pharmacokinetic (PK) parameters. | On Days 14, 28, 42, and 56 | 
| Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. | On Days 14, 28, 42, and 56 | 
| Area Under the Curve (AUC) of Phentermine | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. AUC from time 0 to 24 hours under steady-state. | On Days 14, 28, 42, and 56 | 
| Maximum Concentration (Cmax) of Phentermine | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. | On Days 14, 28, 42, and 56 | 
| Area Under the Curve (AUC) of Topiramate | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. AUC from time 0 to 24 hours under steady-state. | On Days 14, 28, 42, and 56 | 
| Maximum Concentration (Cmax) of Topiramate | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. | On Days 14, 28, 42, and 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Loss | Mean percent weight change from baseline to Day 56 | 56 days | 
| Change in Waist Circumference | Mean change in waist circumference from baseline to Day 56 | 56 days | 
| Change in Blood Pressure | Mean change in blood pressure from baseline to Day 56 | 56 days | 
| Change in OGTT of Fasting and 2-hour Glucose | Mean changes in glycemic parameters (OGTT of fasting and 2-hour glucose) from baseline to Day 56 | 56 days | 
| Change in Lipid Parameters | Mean percent changes in lipid parameters, including total cholesterol, LDL-C, HDL-C and triglycerides (TG) from baseline to Day 56 | 56 days | 
| Change in Visual Analog Scale (VAS) Hunger Scores | Mean change in visual analog scale (VAS) hunger scores from baseline to Day 56. VAS hunger score is measured using a 10.0 cm horizontal line. The left end of this line is defined by word descriptors not at all hungry and corresponds to a VAS hunger score of 0.0. The right end of this line is defined by word descriptors extremely hungry all the time and corresponds to a VAS hunger score of 10.0. Subjects were asked Please mark with a perpendicular line on the scale how hungry you were overall during the past week: to best describes their overall level of hunger during the past week. Research staff measure the distance between the 0.0 = not at all hungry anchor and the mark made by the subject (length to the nearest tenth of a centimeter) to score the measure. | 56 days | 
| Change in Visual Analog Scale (VAS) Satiety Scores | Mean change in visual analog scale (VAS) satiety scores from baseline to Day 56. VAS satiety score is measured using a 10.0 cm horizontal line. The left end of this line is defined by word descriptors very satisfied and corresponds to a VAS satiety score of 0.0. The right end of this line is defined by word descriptors not all at satisfied and corresponds to a VAS satiety score of 10.0. Subjects were asked Please mark with a perpendicular line on the scale how satisfied you were after eating during the past week: to evaluate how satisfied subjects are after eating during the past week. Research staff measure the distance between the 0.0 = very satisfied anchor and the mark made by the subject (length to the nearest tenth of a centimeter) to score the measure. | 56 days | 
| Change in HOMA-IR | Mean changes in glycemic parameters (HOMA-IR) from baseline to Day 56 | 56 days | 
| Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) | Mean changes in glycemic parameters [Whole Body Insulin Sensitivity Index (WBISI) (Matsuda)] from baseline to Day 56. The Oral Glucose Tolerance Test (OGTT) were performed at Baseline and Day 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. | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Qsymia, Adolescent Obesity, Childhood Obesity, Pharmacokinetics, VI-0521, Phentermine, Topiramate