A Pharmacokinetic Study Comparing VI-0521 With Placebo in Obese Adolescents
Sponsor
VIVUS LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02714062
Collaborator
(none)
42
4
3
8
10.5
1.3
Study Details
Study Description
Brief Summary
The primary objective of this study is to describe the pharmacokinetic profiles of VI-0521 in obese adolescents.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, Pharmacokinetic and Pharmacodynamic Study of VI-0521 in Obese Adolescents
Actual Study Start Date
:
Mar 1, 2016
Actual Primary Completion Date
:
Oct 1, 2016
Actual Study Completion Date
:
Nov 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Days 1-56: Placebo |
Drug: Placebo
po once daily
Other Names:
|
| Experimental: 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) |
Drug: VI-0521 Mid Dose
po once daily
Other Names:
|
| Experimental: 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) |
Drug: VI-0521 Top Dose
po once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Weight Loss [56 days]
Mean percent weight change 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.
- 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.
- Change in HOMA-IR [56 days]
Mean changes in glycemic parameters (HOMA-IR) 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Facility | Baton Rouge | Louisiana | United States | 70808 |
| 2 | Research Facility | Marrero | Louisiana | United States | 70072 |
| 3 | Research Facility | Cincinnati | Ohio | United States | 45229 |
| 4 | Research Facility | Charleston | South Carolina | United States | 29403 |
Sponsors and Collaborators
- VIVUS LLC
Investigators
- Principal Investigator: Daniel Hsia, M.D., Pennington Biomedical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
VIVUS LLC
ClinicalTrials.gov Identifier:
NCT02714062
Other Study ID Numbers:
- OB-402
First Posted:
Mar 21, 2016
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by VIVUS LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Period Title: Overall Study | |||
| STARTED | 14 | 15 | 13 |
| COMPLETED | 13 | 14 | 10 |
| NOT COMPLETED | 1 | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | Total |
|---|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) | Total of all reporting groups |
| Overall Participants | 14 | 15 | 13 | 42 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
14.1
(1.56)
|
14.4
(1.30)
|
14.3
(1.55)
|
14.3
(1.44)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
9
64.3%
|
8
53.3%
|
9
69.2%
|
26
61.9%
|
| Male |
5
35.7%
|
7
46.7%
|
4
30.8%
|
16
38.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
1
6.7%
|
0
0%
|
1
2.4%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
11
78.6%
|
7
46.7%
|
6
46.2%
|
24
57.1%
|
| White |
3
21.4%
|
6
40%
|
6
46.2%
|
15
35.7%
|
| More than one race |
0
0%
|
1
6.7%
|
1
7.7%
|
2
4.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
14
100%
|
15
100%
|
13
100%
|
42
100%
|
Outcome Measures
| Title | Apparent Clearance (CL/F) of Phentermine and Topiramate |
|---|---|
| Description | A Bayesian analysis was performed to derive posterior Bayes individual pharmacokinetic (PK) parameters. |
| Time Frame | On Days 14, 28, 42, and 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Phentermine) |
7.33
(1.63)
|
7.04
(2.65)
|
| Day 28 (Phentermine) |
7.33
(1.63)
|
7.18
(2.57)
|
| Day 42 (Phentermine) |
6.82
(1.69)
|
6.49
(2.15)
|
| Day 56 (Phentermine) |
6.82
(1.69)
|
6.67
(2.18)
|
| Day 14 (Topiramate) |
1.32
(0.333)
|
1.25
(0.307)
|
| Day 28 (Topiramate) |
1.32
(0.333)
|
1.27
(0.300)
|
| Day 42 (Topiramate) |
1.25
(0.291)
|
1.20
(0.257)
|
| Day 56 (Topiramate) |
1.25
(0.291)
|
1.18
(0.265)
|
| Title | Apparent Volume of Distribution (Vc/F) of Phentermine and Topiramate |
|---|---|
| Description | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
| Time Frame | On Days 14, 28, 42, and 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Phentermine) |
289
(80.4)
|
289
(70.4)
|
| Day 28 (Phentermine) |
287
(79.8)
|
291
(69.6)
|
| Day 42 (Phentermine) |
284
(79.3)
|
298
(62.1)
|
| Day 56 (Phentermine) |
281
(78.8)
|
299
(64.6)
|
| Day 14 (Topiramate) |
46.8
(17.7)
|
46.1
(13.5)
|
| Day 28 (Topiramate) |
46.2
(17.5)
|
46.6
(13.5)
|
| Day 42 (Topiramate) |
45.7
(17.3)
|
48.2
(11.5)
|
| Day 56 (Topiramate) |
45.2
(17.2)
|
47.5
(12.3)
|
| Title | Area Under the Curve (AUC) of Phentermine |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Phentermine) |
533
(109)
|
600
(205)
|
| Day 28 (Phentermine) |
1066
(218)
|
1171
(403)
|
| Day 42 (Phentermine) |
1154
(240)
|
1902
(576)
|
| Day 56 (Phentermine) |
1154
(240)
|
2469
(775)
|
| Title | Maximum Concentration (Cmax) of Phentermine |
|---|---|
| Description | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
| Time Frame | On Days 14, 28, 42, and 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Phentermine) |
27.6
(5.34)
|
30.3
(9.61)
|
| Day 28 (Phentermine) |
55.3
(10.7)
|
59.3
(19.0)
|
| Day 42 (Phentermine) |
59.0
(11.6)
|
94.2
(25.9)
|
| Day 56 (Phentermine) |
59.1
(11.6)
|
123
(34.8)
|
| Title | Weight Loss |
|---|---|
| Description | Mean percent weight change from baseline to Day 56 |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 15 | 12 |
| Mean (Standard Deviation) [Percent weight change] |
1.14
(2.810)
|
-3.77
(2.446)
|
-4.99
(3.410)
|
| Title | Change in Waist Circumference |
|---|---|
| Description | Mean change in waist circumference from baseline to Day 56 |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 15 | 12 |
| Mean (Standard Deviation) [cm] |
0.1
(4.17)
|
-2.6
(5.63)
|
-4.8
(4.91)
|
| Title | Change in Blood Pressure |
|---|---|
| Description | Mean change in blood pressure from baseline to Day 56 |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 14 | 15 | 13 |
| Mean change in systolic BP |
-6.0
(12.42)
|
-3.3
(10.24)
|
-3.8
(9.64)
|
| Mean change in diastolic BP |
-2.2
(7.53)
|
3.5
(8.11)
|
2.1
(6.10)
|
| Title | Change in OGTT of Fasting and 2-hour Glucose |
|---|---|
| Description | Mean changes in glycemic parameters (OGTT of fasting and 2-hour glucose) from baseline to Day 56 |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 14 | 15 | 13 |
| Mean Change in OGTT of Fasting Serum Glucose |
-3.2
(11.66)
|
0.6
(4.65)
|
-2.1
(9.64)
|
| Mean Change in OGTT of 2-Hour Serum Glucose |
-1.2
(33.23)
|
-3.9
(31.96)
|
-9.3
(16.57)
|
| Mean Change in OGTT of Fasting Serum Insulin |
3.28
(25.463)
|
-10.92
(31.474)
|
-8.03
(6.500)
|
| Mean Change in OGTT of 2-Hour Serum Insulin |
11.45
(123.842)
|
-54.13
(176.897)
|
-92.99
(104.468)
|
| Title | Change in Lipid Parameters |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 14 | 15 | 13 |
| Mean Percent Change in TC |
0.26
(9.154)
|
-6.10
(10.857)
|
-1.73
(14.103)
|
| Mean Percent Change in LDL-C |
2.89
(16.532)
|
-4.42
(13.567)
|
8.99
(26.718)
|
| Mean Percent Change in HDL-C |
-3.16
(20.539)
|
-6.62
(9.887)
|
-12.55
(14.248)
|
| Mean Percent Change in TG |
7.54
(42.040)
|
0.05
(58.326)
|
-8.05
(47.167)
|
| Title | Change in Visual Analog Scale (VAS) Hunger Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 15 | 12 |
| Mean (Standard Deviation) [units on a scale] |
-0.48
(1.975)
|
-1.26
(2.030)
|
-3.28
(2.314)
|
| Title | Change in Visual Analog Scale (VAS) Satiety Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 15 | 12 |
| Mean (Standard Deviation) [units on a scale] |
-0.74
(2.164)
|
-0.65
(1.758)
|
0.18
(2.221)
|
| Title | Area Under the Curve (AUC) of Topiramate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Topiramate) |
18.5
(4.49)
|
19.4
(4.75)
|
| Day 28 (Topiramate) |
37.0
(8.98)
|
38.2
(9.33)
|
| Day 42 (Topiramate) |
38.8
(8.90)
|
60.1
(13.1)
|
| Day 56 (Topiramate) |
38.8
(8.90)
|
81.4
(17.9)
|
| Title | Maximum Concentration (Cmax) of Topiramate |
|---|---|
| Description | A Bayesian analysis was performed to derive posterior Bayes individual PK parameters. |
| Time Frame | On Days 14, 28, 42, and 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|
| Arm/Group Description | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 15 | 13 |
| Day 14 (Topiramate) |
0.917
(0.226)
|
0.952
(0.236)
|
| Day 28 (Topiramate) |
1.84
(0.454)
|
1.88
(0.465)
|
| Day 42 (Topiramate) |
1.92
(0.454)
|
2.90
(0.594)
|
| Day 56 (Topiramate) |
1.92
(0.456)
|
3.93
(0.817)
|
| Title | Change in HOMA-IR |
|---|---|
| Description | Mean changes in glycemic parameters (HOMA-IR) from baseline to Day 56 |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 14 | 10 |
| Mean (Standard Deviation) [μIU/mL] |
0.65
(7.298)
|
-2.46
(7.513)
|
-1.82
(1.444)
|
| Title | Change in Whole Body Insulin Sensitivity Index (WBISI) (Matsuda) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of subjects with values at both time points (Baseline and Day 56) |
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose |
|---|---|---|---|
| Arm/Group Description | Days 1-56: Placebo | Days 1-14: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg) Days 15-56: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg) | 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) |
| Measure Participants | 13 | 13 | 10 |
| Mean (Standard Deviation) [Index] |
-0.19
(1.758)
|
0.55
(1.226)
|
2.13
(2.921)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | |||
| Arm/Group Description | Placebo: Placebo, po once daily | VI-0521 Mid Dose: phentermine 7.5 mg and topiramate 46 mg, po once daily | VI-0521 Top Dose: phentermine 15 mg and topiramate 92 mg, po once daily | |||
All Cause Mortality |
||||||
| Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/14 (0%) | 0/15 (0%) | 0/13 (0%) | |||
Serious Adverse Events |
||||||
| Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscle Spasms | 0/14 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | VI-0521 Mid Dose | VI-0521 Top Dose | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/14 (50%) | 6/15 (40%) | 10/13 (76.9%) | |||
| Eye disorders | ||||||
| Vision blurred | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Gastrointestinal disorders | ||||||
| Dry mouth | 0/14 (0%) | 1/15 (6.7%) | 1/13 (7.7%) | |||
| Abdominal pain upper | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Constipation | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Crohn's disease | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Diarrhoea | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| General disorders | ||||||
| Fatigue | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Influenza like illness | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Infections and infestations | ||||||
| Ear infection | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Nasopharyngitis | 1/14 (7.1%) | 0/15 (0%) | 0/13 (0%) | |||
| Pharyngitis | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Procedural pain | 1/14 (7.1%) | 0/15 (0%) | 0/13 (0%) | |||
| Investigations | ||||||
| Urine analysis abnormal | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Urine osmolarity increased | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/14 (7.1%) | 0/15 (0%) | 2/13 (15.4%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/14 (0%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Nervous system disorders | ||||||
| Headache | 3/14 (21.4%) | 2/15 (13.3%) | 2/13 (15.4%) | |||
| Paraesthesia | 1/14 (7.1%) | 0/15 (0%) | 4/13 (30.8%) | |||
| Hypoaesthesia | 0/14 (0%) | 0/15 (0%) | 2/13 (15.4%) | |||
| Dizziness | 1/14 (7.1%) | 0/15 (0%) | 0/13 (0%) | |||
| Migraine | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Poor quality sleep | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Syncope | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 1/14 (7.1%) | 1/15 (6.7%) | 0/13 (0%) | |||
| Depressed mood | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Oropharyngeal pain | 1/14 (7.1%) | 0/15 (0%) | 0/13 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
| Skin hyperpigmentation | 0/14 (0%) | 0/15 (0%) | 1/13 (7.7%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The PI may publish the result of the study 12 months or longer after termination of the study. The PI will provide the sponsor a copy of any proposed publication at least 30 days prior to submission for publication.
Results Point of Contact
| Name/Title | Sr. Director, Clinical Research |
|---|---|
| Organization | VIVUS |
| Phone | 650-934-5200 |
Responsible Party:
VIVUS LLC
ClinicalTrials.gov Identifier:
NCT02714062
Other Study ID Numbers:
- OB-402
First Posted:
Mar 21, 2016
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022