Childhood Obesity, Pediatric Obesity
Conditions
Keywords
Adolescent Obesity, Childhood Obesity, Qsymia, Pharmacokinetics, VI-0521, Phentermine, Topiramate
Brief summary
The primary objective of this study is to describe the pharmacokinetic profiles of VI-0521 in obese adolescents.
Interventions
DRUGPlacebo
po once daily
DRUGVI-0521 Mid Dose
po once daily
DRUGVI-0521 Top Dose
po once daily
Sponsors
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Clearance (CL/F) of Phentermine and Topiramate | On Days 14, 28, 42, and 56 | A Bayesian analysis was performed to derive posterior Bayes individual pharmacokinetic (PK) parameters. |
| Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | On Days 14, 28, 42, and 56 | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
| Area Under the Curve (AUC) of Phentermine | 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. |
| Maximum Concentration (Cmax) of Phentermine | On Days 14, 28, 42, and 56 | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
| Area Under the Curve (AUC) of Topiramate | 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. |
| Maximum Concentration (Cmax) of Topiramate | On Days 14, 28, 42, and 56 | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale (VAS) Satiety Scores | 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. |
| Weight Loss | 56 days | Mean percent weight change from baseline to Day 56 |
| Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) | 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. |
| Change in HOMA-IR | 56 days | Mean changes in glycemic parameters (HOMA-IR) from baseline to Day 56 |
| Change in Waist Circumference | 56 days | Mean change in waist circumference from baseline to Day 56 |
| Change in Blood Pressure | 56 days | Mean change in blood pressure from baseline to Day 56 |
| Change in OGTT of Fasting and 2-hour Glucose | 56 days | Mean changes in glycemic parameters (OGTT of fasting and 2-hour glucose) from baseline to Day 56 |
| Change in Lipid Parameters | 56 days | Mean percent changes in lipid parameters, including total cholesterol, LDL-C, HDL-C and triglycerides (TG) from baseline to Day 56 |
| Change in Visual Analog Scale (VAS) Hunger Scores | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Days 1-56: Placebo | 14 |
| 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) | 15 |
| 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) | 13 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | VI-0521 Top Dose | VI-0521 Mid Dose |
|---|---|---|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 1.56 | 14.3 years STANDARD_DEVIATION 1.44 | 14.3 years STANDARD_DEVIATION 1.55 | 14.4 years STANDARD_DEVIATION 1.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 24 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 15 Participants | 6 Participants | 6 Participants |
| Region of Enrollment United States | 14 Participants | 42 Participants | 13 Participants | 15 Participants |
| Sex: Female, Male Female | 9 Participants | 26 Participants | 9 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 7 / 14 | 6 / 15 | 10 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 | 1 / 13 |
Outcome results
Primary
Apparent Clearance (CL/F) of Phentermine and Topiramate
A Bayesian analysis was performed to derive posterior Bayes individual pharmacokinetic (PK) parameters.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 14 (Phentermine) | 7.33 L/h | Standard Deviation 1.63 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 14 (Topiramate) | 1.32 L/h | Standard Deviation 0.333 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 42 (Phentermine) | 6.82 L/h | Standard Deviation 1.69 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 28 (Topiramate) | 1.32 L/h | Standard Deviation 0.333 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 28 (Phentermine) | 7.33 L/h | Standard Deviation 1.63 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 42 (Topiramate) | 1.25 L/h | Standard Deviation 0.291 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 56 (Phentermine) | 6.82 L/h | Standard Deviation 1.69 |
| VI-0521 Mid Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 56 (Topiramate) | 1.25 L/h | Standard Deviation 0.291 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 56 (Phentermine) | 6.67 L/h | Standard Deviation 2.18 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 14 (Phentermine) | 7.04 L/h | Standard Deviation 2.65 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 28 (Phentermine) | 7.18 L/h | Standard Deviation 2.57 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 42 (Phentermine) | 6.49 L/h | Standard Deviation 2.15 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 56 (Topiramate) | 1.18 L/h | Standard Deviation 0.265 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 14 (Topiramate) | 1.25 L/h | Standard Deviation 0.307 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 28 (Topiramate) | 1.27 L/h | Standard Deviation 0.3 |
| VI-0521 Top Dose | Apparent Clearance (CL/F) of Phentermine and Topiramate | Day 42 (Topiramate) | 1.20 L/h | Standard Deviation 0.257 |
Primary
Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate
A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 14 (Phentermine) | 289 L | Standard Deviation 80.4 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 28 (Phentermine) | 287 L | Standard Deviation 79.8 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 42 (Phentermine) | 284 L | Standard Deviation 79.3 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 56 (Phentermine) | 281 L | Standard Deviation 78.8 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 14 (Topiramate) | 46.8 L | Standard Deviation 17.7 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 28 (Topiramate) | 46.2 L | Standard Deviation 17.5 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 42 (Topiramate) | 45.7 L | Standard Deviation 17.3 |
| VI-0521 Mid Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 56 (Topiramate) | 45.2 L | Standard Deviation 17.2 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 56 (Topiramate) | 47.5 L | Standard Deviation 12.3 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 14 (Phentermine) | 289 L | Standard Deviation 70.4 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 14 (Topiramate) | 46.1 L | Standard Deviation 13.5 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 28 (Phentermine) | 291 L | Standard Deviation 69.6 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 42 (Topiramate) | 48.2 L | Standard Deviation 11.5 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 42 (Phentermine) | 298 L | Standard Deviation 62.1 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 28 (Topiramate) | 46.6 L | Standard Deviation 13.5 |
| VI-0521 Top Dose | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate | Day 56 (Phentermine) | 299 L | Standard Deviation 64.6 |
Primary
Area Under the Curve (AUC) of Phentermine
A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. AUC from time 0 to 24 hours under steady-state.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Phentermine | Day 14 (Phentermine) | 533 ng•h/mL | Standard Deviation 109 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Phentermine | Day 28 (Phentermine) | 1066 ng•h/mL | Standard Deviation 218 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Phentermine | Day 42 (Phentermine) | 1154 ng•h/mL | Standard Deviation 240 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Phentermine | Day 56 (Phentermine) | 1154 ng•h/mL | Standard Deviation 240 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Phentermine | Day 56 (Phentermine) | 2469 ng•h/mL | Standard Deviation 775 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Phentermine | Day 14 (Phentermine) | 600 ng•h/mL | Standard Deviation 205 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Phentermine | Day 42 (Phentermine) | 1902 ng•h/mL | Standard Deviation 576 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Phentermine | Day 28 (Phentermine) | 1171 ng•h/mL | Standard Deviation 403 |
Primary
Area Under the Curve (AUC) of Topiramate
A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. AUC from time 0 to 24 hours under steady-state.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Topiramate | Day 14 (Topiramate) | 18.5 μg•h/mL | Standard Deviation 4.49 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Topiramate | Day 28 (Topiramate) | 37.0 μg•h/mL | Standard Deviation 8.98 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Topiramate | Day 42 (Topiramate) | 38.8 μg•h/mL | Standard Deviation 8.9 |
| VI-0521 Mid Dose | Area Under the Curve (AUC) of Topiramate | Day 56 (Topiramate) | 38.8 μg•h/mL | Standard Deviation 8.9 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Topiramate | Day 56 (Topiramate) | 81.4 μg•h/mL | Standard Deviation 17.9 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Topiramate | Day 14 (Topiramate) | 19.4 μg•h/mL | Standard Deviation 4.75 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Topiramate | Day 42 (Topiramate) | 60.1 μg•h/mL | Standard Deviation 13.1 |
| VI-0521 Top Dose | Area Under the Curve (AUC) of Topiramate | Day 28 (Topiramate) | 38.2 μg•h/mL | Standard Deviation 9.33 |
Primary
Maximum Concentration (Cmax) of Phentermine
A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Phentermine | Day 14 (Phentermine) | 27.6 ng/mL | Standard Deviation 5.34 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Phentermine | Day 28 (Phentermine) | 55.3 ng/mL | Standard Deviation 10.7 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Phentermine | Day 42 (Phentermine) | 59.0 ng/mL | Standard Deviation 11.6 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Phentermine | Day 56 (Phentermine) | 59.1 ng/mL | Standard Deviation 11.6 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Phentermine | Day 56 (Phentermine) | 123 ng/mL | Standard Deviation 34.8 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Phentermine | Day 14 (Phentermine) | 30.3 ng/mL | Standard Deviation 9.61 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Phentermine | Day 42 (Phentermine) | 94.2 ng/mL | Standard Deviation 25.9 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Phentermine | Day 28 (Phentermine) | 59.3 ng/mL | Standard Deviation 19 |
Primary
Maximum Concentration (Cmax) of Topiramate
A Bayesian analysis was performed to derive posterior Bayes individual PK parameters.
Time frame: On Days 14, 28, 42, and 56
Population: PK samples were not collected for some patients due to withdrawal, or missed visits, etc. As a result, number analyzed for some visits is less than overall number analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Topiramate | Day 42 (Topiramate) | 1.92 μg/mL | Standard Deviation 0.454 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Topiramate | Day 14 (Topiramate) | 0.917 μg/mL | Standard Deviation 0.226 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Topiramate | Day 56 (Topiramate) | 1.92 μg/mL | Standard Deviation 0.456 |
| VI-0521 Mid Dose | Maximum Concentration (Cmax) of Topiramate | Day 28 (Topiramate) | 1.84 μg/mL | Standard Deviation 0.454 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Topiramate | Day 56 (Topiramate) | 3.93 μg/mL | Standard Deviation 0.817 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Topiramate | Day 28 (Topiramate) | 1.88 μg/mL | Standard Deviation 0.465 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Topiramate | Day 42 (Topiramate) | 2.90 μg/mL | Standard Deviation 0.594 |
| VI-0521 Top Dose | Maximum Concentration (Cmax) of Topiramate | Day 14 (Topiramate) | 0.952 μg/mL | Standard Deviation 0.236 |
Secondary
Change in Blood Pressure
Mean change in blood pressure from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Change in Blood Pressure | Mean change in systolic BP | -6.0 mmHg | Standard Deviation 12.42 |
| VI-0521 Mid Dose | Change in Blood Pressure | Mean change in diastolic BP | -2.2 mmHg | Standard Deviation 7.53 |
| VI-0521 Top Dose | Change in Blood Pressure | Mean change in systolic BP | -3.3 mmHg | Standard Deviation 10.24 |
| VI-0521 Top Dose | Change in Blood Pressure | Mean change in diastolic BP | 3.5 mmHg | Standard Deviation 8.11 |
| VI-0521 Top Dose | Change in Blood Pressure | Mean change in systolic BP | -3.8 mmHg | Standard Deviation 9.64 |
| VI-0521 Top Dose | Change in Blood Pressure | Mean change in diastolic BP | 2.1 mmHg | Standard Deviation 6.1 |
Secondary
Change in HOMA-IR
Mean changes in glycemic parameters (HOMA-IR) from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Change in HOMA-IR | 0.65 μIU/mL | Standard Deviation 7.298 |
| VI-0521 Top Dose | Change in HOMA-IR | -2.46 μIU/mL | Standard Deviation 7.513 |
| VI-0521 Top Dose | Change in HOMA-IR | -1.82 μIU/mL | Standard Deviation 1.444 |
Secondary
Change in Lipid Parameters
Mean percent changes in lipid parameters, including total cholesterol, LDL-C, HDL-C and triglycerides (TG) from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Change in Lipid Parameters | Mean Percent Change in HDL-C | -3.16 Percent Change | Standard Deviation 20.539 |
| VI-0521 Mid Dose | Change in Lipid Parameters | Mean Percent Change in TG | 7.54 Percent Change | Standard Deviation 42.04 |
| VI-0521 Mid Dose | Change in Lipid Parameters | Mean Percent Change in LDL-C | 2.89 Percent Change | Standard Deviation 16.532 |
| VI-0521 Mid Dose | Change in Lipid Parameters | Mean Percent Change in TC | 0.26 Percent Change | Standard Deviation 9.154 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in TC | -6.10 Percent Change | Standard Deviation 10.857 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in LDL-C | -4.42 Percent Change | Standard Deviation 13.567 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in TG | 0.05 Percent Change | Standard Deviation 58.326 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in HDL-C | -6.62 Percent Change | Standard Deviation 9.887 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in TG | -8.05 Percent Change | Standard Deviation 47.167 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in TC | -1.73 Percent Change | Standard Deviation 14.103 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in LDL-C | 8.99 Percent Change | Standard Deviation 26.718 |
| VI-0521 Top Dose | Change in Lipid Parameters | Mean Percent Change in HDL-C | -12.55 Percent Change | Standard Deviation 14.248 |
Secondary
Change in OGTT of Fasting and 2-hour Glucose
Mean changes in glycemic parameters (OGTT of fasting and 2-hour glucose) from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Mid Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Glucose | -3.2 mg/dL | Standard Deviation 11.66 |
| VI-0521 Mid Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Glucose | -1.2 mg/dL | Standard Deviation 33.23 |
| VI-0521 Mid Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Insulin | 3.28 mg/dL | Standard Deviation 25.463 |
| VI-0521 Mid Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Insulin | 11.45 mg/dL | Standard Deviation 123.842 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Insulin | -54.13 mg/dL | Standard Deviation 176.897 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Glucose | 0.6 mg/dL | Standard Deviation 4.65 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Insulin | -10.92 mg/dL | Standard Deviation 31.474 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Glucose | -3.9 mg/dL | Standard Deviation 31.96 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Insulin | -92.99 mg/dL | Standard Deviation 104.468 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of 2-Hour Serum Glucose | -9.3 mg/dL | Standard Deviation 16.57 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Insulin | -8.03 mg/dL | Standard Deviation 6.5 |
| VI-0521 Top Dose | Change in OGTT of Fasting and 2-hour Glucose | Mean Change in OGTT of Fasting Serum Glucose | -2.1 mg/dL | Standard Deviation 9.64 |
Secondary
Change in Visual Analog Scale (VAS) Hunger Scores
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.
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Change in Visual Analog Scale (VAS) Hunger Scores | -0.48 units on a scale | Standard Deviation 1.975 |
| VI-0521 Top Dose | Change in Visual Analog Scale (VAS) Hunger Scores | -1.26 units on a scale | Standard Deviation 2.03 |
| VI-0521 Top Dose | Change in Visual Analog Scale (VAS) Hunger Scores | -3.28 units on a scale | Standard Deviation 2.314 |
Secondary
Change in Visual Analog Scale (VAS) Satiety Scores
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.
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Change in Visual Analog Scale (VAS) Satiety Scores | -0.74 units on a scale | Standard Deviation 2.164 |
| VI-0521 Top Dose | Change in Visual Analog Scale (VAS) Satiety Scores | -0.65 units on a scale | Standard Deviation 1.758 |
| VI-0521 Top Dose | Change in Visual Analog Scale (VAS) Satiety Scores | 0.18 units on a scale | Standard Deviation 2.221 |
Secondary
Change in Waist Circumference
Mean change in waist circumference from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Change in Waist Circumference | 0.1 cm | Standard Deviation 4.17 |
| VI-0521 Top Dose | Change in Waist Circumference | -2.6 cm | Standard Deviation 5.63 |
| VI-0521 Top Dose | Change in Waist Circumference | -4.8 cm | Standard Deviation 4.91 |
Secondary
Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda)
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.
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) | -0.19 Index | Standard Deviation 1.758 |
| VI-0521 Top Dose | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) | 0.55 Index | Standard Deviation 1.226 |
| VI-0521 Top Dose | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) | 2.13 Index | Standard Deviation 2.921 |
Secondary
Weight Loss
Mean percent weight change from baseline to Day 56
Time frame: 56 days
Population: The number of subjects with values at both time points (Baseline and Day 56)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Mid Dose | Weight Loss | 1.14 Percent weight change | Standard Deviation 2.81 |
| VI-0521 Top Dose | Weight Loss | -3.77 Percent weight change | Standard Deviation 2.446 |
| VI-0521 Top Dose | Weight Loss | -4.99 Percent weight change | Standard Deviation 3.41 |