• Percentage of subjects achieving at least 5% BMI reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
• Percentage of subjects achieving at least 10% BMI reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
• Percentage of subjects achieving at least 15% BMI reduction at Week 56 [ Time Frame: Baseline to Week 56 ]
• Change in waist circumference at Week 56 [ Time Frame: Baseline to Week 56 ]
• Change in Whole Body Insulin Sensitivity Index at Week 56 [ Time Frame: Baseline to Week 56 ]
• Change in fasting insulin at Week 56 [ Time Frame: Baseline to Week 56 ]
• Change in triglycerides at Week 56 [ Time Frame: Baseline to Week 56 ]
• Change in HDL-C (High-Density Lipoprotein Cholesterol) at Week 56 [ Time Frame: Baseline to Week 56 ]

• Adolescent Obesity
• Obesity in Adolescence
• Adolescent Overweight

• Drug: VI-0521 oral capsule
  Phentermine/Topiramate
  Other Names:

  • Qsymia
  • Phentermine and topiramate
• Drug: Placebo oral capsule
  Inactive drug

• 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
  Intervention: Drug: VI-0521 oral capsule
• 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
  Intervention: Drug: VI-0521 oral capsule
• Placebo Comparator: Placebo
  Subjects will receive placebo oral capsule, once daily for up to 56 weeks
  Intervention: Drug: Placebo oral capsule

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 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, GABA analogues, hydantoins, phenyltriazines, succinimides, and other agents (valproic acid and its derivatives, carbamazepine and its derivatives, zonisamide, and felbamate);
  • Tricyclic antidepressants, MAOIs, lithium, levodopa, and dopamine receptor agonists;
  • Carbonic anhydrase inhibitors;
  • Insulin, SFUs, GLP-1 agonists, 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.