Adolescent Obesity, Adolescent Overweight, Obesity in Adolescence
Conditions
Keywords
weight loss, obesity, weight control
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.
Interventions
DRUGVI-0521 oral capsule
Phentermine/Topiramate
DRUGPlacebo oral capsule
Inactive drug
BEHAVIORALLifestyle Modification
The lifestyle modification includes physical activity, behavior change, reduced calorie diet advice, and family support. This intervention is applied to all treatment groups.
Sponsors
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 16 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean % Change in Body Mass Index (BMI) | Baseline to Week 56 | Mean % change in BMI from Baseline to Week 56 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Triglycerides From Baseline to Week 56 | Baseline, Week 56 | — |
| Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 | Baseline to 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 | — |
| Change in Fasting Insulin at Week 56 | Baseline, Week 56 | Change in fasting insulin 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. |
| 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 | — |
| Change From Baseline in Diastolic Blood Pressure at Week 56 | Baseline, Week 56 | — |
| Change in Waist Circumference at Week 56 | Baseline, Week 56 | Change in waist circumference from Baseline to Week 56 |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 26 study sites in the United States.
Pre-assignment details
The study consisted of a Screening period of up to 28 days. Once confirmed participant meeting all study criteria, including laboratory values, participants were randomized to either placebo, Mid-dose, or Top-dose of VI-0521 (phentermine/topiramate \[PHEN/TPM\]), for a 56-week treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Weeks 1-56: Placebo (Inactive drug) oral capsule, once daily; Weeks 1-56: Lifestyle Modification | 56 |
| VI-0521 Mid Dose Weeks 1-2: VI-0521 (PHEN/TPM 3.75 mg/23 mg) oral capsule, once daily; Weeks 3-56: VI-0521 (PHEN/TPM 7.5 mg/46 mg) oral capsule, once daily; Weeks 1-56: Lifestyle Modification | 54 |
| VI-0521 Top Dose Weeks 1-2: VI-0521 (PHEN/TPM 3.75 mg/23 mg) oral capsule, once daily; Weeks 3-12: VI-0521 (PHEN/TPM 7.5 mg/46 mg) oral capsule, once daily; Weeks 13-14: VI-0521 (PHEN/TPM 11.25 mg/69 mg) oral capsule, once daily; Weeks 15-56: VI-0521 (PHEN/TPM 15 mg/92 mg) oral capsule, once daily; Weeks 1-56: Lifestyle Modification | 113 |
| Total | 223 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 |
| Overall Study | All Other Personal Reasons | 1 | 1 | 2 |
| Overall Study | Lack of Efficacy | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 13 | 9 | 20 |
| Overall Study | Protocol Non-Compliance | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject / Parent / Legal Guardian | 10 | 6 | 14 |
Baseline characteristics
| Characteristic | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 14.0 years | 14.1 years | 13.9 years | 14.0 years |
| Age, Customized 12-14 Years | 34 Participants | 33 Participants | 69 Participants | 136 Participants |
| Age, Customized 15-16 Years | 22 Participants | 21 Participants | 44 Participants | 87 Participants |
| BMI Categories ≥95th to <99th percentile | 26 Participants | 23 Participants | 33 Participants | 82 Participants |
| BMI Categories ≥99th percentile | 30 Participants | 30 Participants | 79 Participants | 139 Participants |
| BMI Categories Missing | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 25 Participants | 34 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 28 Participants | 79 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 14 Participants | 36 Participants | 60 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 42 Participants | 36 Participants | 71 Participants | 149 Participants |
| Region of Enrollment United States | 56 participants | 54 participants | 113 participants | 223 participants |
| Sex: Female, Male Female | 30 Participants | 28 Participants | 63 Participants | 121 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 50 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 54 | 0 / 113 |
| other Total, other adverse events | 20 / 56 | 11 / 54 | 18 / 113 |
| serious Total, serious adverse events | 0 / 56 | 0 / 54 | 2 / 113 |
Outcome results
Primary
Mean % Change in Body Mass Index (BMI)
Mean % change in BMI from Baseline to Week 56
Time frame: Baseline to Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean % Change in Body Mass Index (BMI) | 3.34 Percentage Change | Standard Error 1.441 |
| VI-0521 Mid Dose | Mean % Change in Body Mass Index (BMI) | -4.78 Percentage Change | Standard Error 1.302 |
| VI-0521 Top Dose | Mean % Change in Body Mass Index (BMI) | -7.11 Percentage Change | Standard Error 1.011 |
p-value: <0.0001Mixed Models Analysis
Secondary
Change From Baseline in Diastolic Blood Pressure at Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure at Week 56 | 3.41 mmHg | Standard Error 1.51 |
| VI-0521 Mid Dose | Change From Baseline in Diastolic Blood Pressure at Week 56 | 0.24 mmHg | Standard Error 1.322 |
| VI-0521 Top Dose | Change From Baseline in Diastolic Blood Pressure at Week 56 | 1.22 mmHg | Standard Error 0.989 |
Secondary
Change From Baseline in Systolic Blood Pressure at Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 56 | 2.86 mmHg | Standard Error 1.63 |
| VI-0521 Mid Dose | Change From Baseline in Systolic Blood Pressure at Week 56 | 0.09 mmHg | Standard Error 1.503 |
| VI-0521 Top Dose | Change From Baseline in Systolic Blood Pressure at Week 56 | 1.84 mmHg | Standard Error 1.111 |
Secondary
Change in Fasting Insulin at Week 56
Change in fasting insulin from Baseline to Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Fasting Insulin at Week 56 | -3.32 uIU/mL | Standard Error 8.956 |
| VI-0521 Mid Dose | Change in Fasting Insulin at Week 56 | -11.47 uIU/mL | Standard Error 7.433 |
| VI-0521 Top Dose | Change in Fasting Insulin at Week 56 | -7.99 uIU/mL | Standard Error 6.299 |
Secondary
Change in Waist Circumference at Week 56
Change in waist circumference from Baseline to Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Waist Circumference at Week 56 | 0.61 Centimeter | Standard Error 1.397 |
| VI-0521 Mid Dose | Change in Waist Circumference at Week 56 | -5.03 Centimeter | Standard Error 1.376 |
| VI-0521 Top Dose | Change in Waist Circumference at Week 56 | -6.98 Centimeter | Standard Error 1.072 |
Secondary
Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at 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.
Time frame: Baseline, Week 56
Population: The number of subjects with values at both time points (Baseline and Week 56)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56 | -3.7 Index | Standard Error 8.887 |
| VI-0521 Mid Dose | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56 | -3.93 Index | Standard Error 7.647 |
| VI-0521 Top Dose | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) at Week 56 | -2.99 Index | Standard Error 6.445 |
Secondary
Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56
Time frame: Baseline to Week 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56 | 4.5 percentage of participants |
| VI-0521 Mid Dose | Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56 | 33.5 percentage of participants |
| VI-0521 Top Dose | Percentage of Subjects Achieving at Least 10% BMI Reduction at Week 56 | 44.4 percentage of participants |
Secondary
Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56
Time frame: Baseline to Week 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56 | 2.9 percentage of participants |
| VI-0521 Mid Dose | Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56 | 13.6 percentage of participants |
| VI-0521 Top Dose | Percentage of Subjects Achieving at Least 15% BMI Reduction at Week 56 | 28.9 percentage of participants |
Secondary
Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56
Time frame: Baseline to Week 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 | 13.6 percentage of participants |
| VI-0521 Mid Dose | Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 | 44 percentage of participants |
| VI-0521 Top Dose | Percentage of Subjects Achieving at Least 5% BMI Reduction at Week 56 | 52.2 percentage of participants |
p-value: <0.0017Cochran-Mantel-Haenszel
Secondary
Percent Change in HDL-C From Baseline to Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in HDL-C From Baseline to Week 56 | -4.3 Percent Change | Standard Error 15.1 |
| VI-0521 Mid Dose | Percent Change in HDL-C From Baseline to Week 56 | 2.11 Percent Change | Standard Error 11.501 |
| VI-0521 Top Dose | Percent Change in HDL-C From Baseline to Week 56 | 0.65 Percent Change | Standard Error 9.561 |
p-value: 0.7465Mixed Models Analysis
Secondary
Percent Change in Triglycerides From Baseline to Week 56
Time frame: Baseline, Week 56
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Week 56 | 5.56 Percent Change | Standard Error 8.407 |
| VI-0521 Mid Dose | Percent Change in Triglycerides From Baseline to Week 56 | -6.18 Percent Change | Standard Error 7.958 |
| VI-0521 Top Dose | Percent Change in Triglycerides From Baseline to Week 56 | -5.59 Percent Change | Standard Error 7.17 |