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

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

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

Study Overview

• Status: Completed
• Conditions: Pediatric Obesity; Childhood Obesity
• Intervention / Treatment: Drug: Placebo; Drug: VI-0521 Mid Dose; Drug: VI-0521 Top Dose

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Research Facility
    • Marrero, Louisiana, United States, 70072
      • Research Facility
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Facility
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Days 1-56: Placebo	Drug: Placebo; po once daily; Other Names: Sugar Pill
Experimental: 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)	Drug: VI-0521 Mid Dose; po once daily; Other Names: Phentermine/Topiramate
Experimental: 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)	Drug: VI-0521 Top Dose; po once daily; Other Names: Phentermine/Topiramate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VIVUS LLC
• Investigators: Principal Investigator: Daniel Hsia, M.D., Pennington Biomedical Research

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: March 15, 2016
• First Posted (Estimate): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Childhood Obesity; Pharmacokinetics; Adolescent Obesity; Topiramate; Phentermine; Qsymia; VI-0521
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anticonvulsants; Appetite Depressants; Anti-Obesity Agents; Central Nervous System Stimulants; Sympathomimetics; Topiramate; Phentermine
• Other Study ID Numbers: OB-402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No