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

• ClinicalTrials.gov Identifier: NCT03922945
• Recruitment Status: Completed
• First Posted: April 22, 2019
• Results First Posted: September 10, 2022
• Last Update Posted: September 10, 2022
• Sponsor: VIVUS LLC
• Information provided by (Responsible Party): VIVUS LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Adolescent Obesity; Obesity in Adolescence; Adolescent Overweight	Drug: VI-0521 oral capsule; Drug: Placebo oral capsule; Behavioral: Lifestyle Modification	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 223 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 2, 2019
• Actual Primary Completion Date: April 16, 2021
• Actual Study Completion Date: April 16, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: VI-0521 Mid Dose (Phentermine 7.5 mg +Topiramate 46 mg); 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; Phentermine/Topiramate; Other Names: Qsymia; Phentermine and topiramate; Behavioral: Lifestyle Modification; The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.
Experimental: VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg); 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; Phentermine/Topiramate; Other Names: Qsymia; Phentermine and topiramate; Behavioral: Lifestyle Modification; The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.
Placebo Comparator: Placebo; Subjects will receive placebo oral capsule, once daily for up to 56 weeks	Drug: Placebo oral capsule; Inactive drug; Behavioral: Lifestyle Modification; The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.

Outcome Measures

Primary Outcome Measures :

1. Mean % Change in Body Mass Index (BMI) [ Time Frame: Baseline to Week 56 ]
   Mean % change in BMI from Baseline to Week 56

Secondary Outcome Measures :

1. Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
2. Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
3. Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
4. Change in Waist Circumference at Week 56 [ Time Frame: Baseline, Week 56 ]
   Change in waist circumference from Baseline to Week 56
5. Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56 [ Time Frame: Baseline, 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.
6. Change in Fasting Insulin at Week 56 [ Time Frame: Baseline, Week 56 ]
   Change in fasting insulin from Baseline to Week 56
7. Percent Change in Triglycerides From Baseline to Week 56 [ Time Frame: Baseline, Week 56 ]
8. Percent Change in HDL-C From Baseline to Week 56 [ Time Frame: Baseline, Week 56 ]
9. Change From Baseline in Systolic Blood Pressure at Week 56 [ Time Frame: Baseline, Week 56 ]
10. Change From Baseline in Diastolic Blood Pressure at Week 56 [ Time Frame: Baseline, Week 56 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Oklahoma

Intend Research, LLC

Norman, Oklahoma, United States, 73069

Sponsors and Collaborators

VIVUS LLC

  Study Documents (Full-Text)

Documents provided by VIVUS LLC:

Study Protocol  [PDF] June 21, 2019

Statistical Analysis Plan  [PDF] April 1, 2021

More Information

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT03922945
• Other Study ID Numbers: OB-403
• First Posted: April 22, 2019
• Results First Posted: September 10, 2022
• Last Update Posted: September 10, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by VIVUS LLC:

weight loss; obesity; weight control

Additional relevant MeSH terms:

Obesity; Overweight; Pediatric Obesity; Overnutrition; Nutrition Disorders; 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