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

Phase 4

Completed

Conditions: Adolescent Obesity
Obesity in Adolescence
Adolescent Overweight

Interventions: Drug: VI-0521 oral capsule
Drug: Placebo oral capsule
Behavioral: Lifestyle Modification

Registration Number: NCT03922945

Lead Sponsor: VIVUS LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 223

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VI-0521 Mid Dose (Phentermine 7.5 mg +Topiramate 46 mg)	VI-0521 oral capsule	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
VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg)	Lifestyle Modification	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
Placebo	Placebo oral capsule	Subjects will receive placebo oral capsule, once daily for up to 56 weeks
VI-0521 Mid Dose (Phentermine 7.5 mg +Topiramate 46 mg)	Lifestyle Modification	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
VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg)	VI-0521 oral capsule	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
Placebo	Lifestyle Modification	Subjects will receive placebo oral capsule, once daily for up to 56 weeks

Primary Outcome Measures

Name	Time	Method
Mean % Change in Body Mass Index (BMI)	Baseline to Week 56	Mean % change in BMI from Baseline to Week 56

Secondary Outcome Measures

Name	Time	Method
Percent Change in HDL-C From Baseline to Week 56	Baseline, Week 56
Change From Baseline in Systolic Blood Pressure at Week 56	Baseline, Week 56
Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56	Baseline to Week 56
Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56	Baseline to Week 56
Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56	Baseline to Week 56
Change in Waist Circumference at Week 56	Baseline, Week 56	Change in waist circumference from Baseline to Week 56
Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56	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.
Change in Fasting Insulin at Week 56	Baseline, Week 56	Change in fasting insulin from Baseline to Week 56
Percent Change in Triglycerides From Baseline to Week 56	Baseline, Week 56
Change From Baseline in Diastolic Blood Pressure at Week 56	Baseline, Week 56