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

• ClinicalTrials.gov Identifier: NCT02714062
• Recruitment Status: Completed
• First Posted: March 21, 2016
• Results First Posted: February 5, 2018
• Last Update Posted: March 7, 2018
• Sponsor: VIVUS LLC
• Information provided by (Responsible Party): VIVUS LLC

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pediatric Obesity; Childhood Obesity	Drug: Placebo; Drug: VI-0521 Mid Dose; Drug: VI-0521 Top Dose	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Pharmacokinetic and Pharmacodynamic Study of VI-0521 in Obese Adolescents
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Days 1-56: Placebo	Drug: Placebo; po once daily; Other Name: 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 Name: 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 Name: Phentermine/Topiramate

Outcome Measures

Primary Outcome Measures :

1. Apparent Clearance (CL/F) of Phentermine and Topiramate [ Time Frame: On Days 14, 28, 42, and 56 ]
   A Bayesian analysis was performed to derive posterior Bayes individual pharmacokinetic (PK) parameters.
2. Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate [ Time Frame: On Days 14, 28, 42, and 56 ]
   A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.
3. Area Under the Curve (AUC) of Phentermine [ Time Frame: 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.
4. Maximum Concentration (Cmax) of Phentermine [ Time Frame: On Days 14, 28, 42, and 56 ]
   A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.
5. Area Under the Curve (AUC) of Topiramate [ Time Frame: 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.
6. Maximum Concentration (Cmax) of Topiramate [ Time Frame: On Days 14, 28, 42, and 56 ]
   A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Louisiana

Research Facility

Baton Rouge, Louisiana, United States, 70808

Research Facility

Marrero, Louisiana, United States, 70072

United States, Ohio

Research Facility

Cincinnati, Ohio, United States, 45229

United States, South Carolina

Research Facility

Charleston, South Carolina, United States, 29403

Sponsors and Collaborators

VIVUS LLC

Investigators

• Principal Investigator: Daniel Hsia, M.D.; Pennington Biomedical Research

More Information

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT02714062
• Other Study ID Numbers: OB-402
• First Posted: March 21, 2016
• Results First Posted: February 5, 2018
• Last Update Posted: March 7, 2018
• Last Verified: February 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by VIVUS LLC:

Adolescent Obesity; Childhood Obesity; Qsymia; Pharmacokinetics; VI-0521; Phentermine; Topiramate

Additional relevant MeSH terms:

Obesity; Pediatric Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Topiramate; Phentermine; Anticonvulsants; Hypoglycemic Agents; Physiological Effects of Drugs; Central Nervous System Stimulants; Appetite Depressants; Anti-Obesity Agents; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action