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

Phase 4

Completed

Conditions: Pediatric Obesity
Childhood Obesity

Interventions: Drug: VI-0521 Mid Dose
Drug: Placebo
Drug: VI-0521 Top Dose

Registration Number: NCT02714062

Lead Sponsor: VIVUS LLC

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VI-0521 Mid Dose	VI-0521 Mid Dose	* Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) * Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg)
Placebo	Placebo	Days 1-56: Placebo
VI-0521 Top Dose	VI-0521 Top Dose	* 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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in HOMA-IR	56 days	Mean changes in glycemic parameters (HOMA-IR) from baseline to Day 56
Weight Loss	56 days	Mean percent weight change from baseline to Day 56
Change in Blood Pressure	56 days	Mean change in blood pressure from baseline to Day 56
Change in Visual Analog Scale (VAS) Satiety Scores	56 days	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.
Change in Lipid Parameters	56 days	Mean percent changes in lipid parameters, including total cholesterol, LDL-C, HDL-C and triglycerides (TG) from baseline to Day 56
Change in Waist Circumference	56 days	Mean change in waist circumference from baseline to Day 56
Change in OGTT of Fasting and 2-hour Glucose	56 days	Mean changes in glycemic parameters (OGTT of fasting and 2-hour glucose) from baseline to Day 56
Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda)	56 days	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.
Change in Visual Analog Scale (VAS) Hunger Scores	56 days	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.