Obesity, Overweight
Conditions
Keywords
Overweight, Obesity, coordination, psychomotor
Brief summary
The purpose of this study is to determine how VI-0521 affect speed and reaction time on specific tasks that require eye and hand coordination, compared to placebo.
Interventions
DRUGVI-0521
Phentermine 3.75 mg and topiramate 23 mg daily for the 1st week; Phentermine 7.5 mg and topiramate 46 mg daily for the 2nd week; Phentermine 11.25 mg and topiramate 69 mg daily for the 3rd week; Phentermine 15 mg and topiramate 92 mg daily for the 4th week
DRUGPlacebo
Placebo daily for 4 weeks
OTHERAlcohol
OTHERalcohol placebo
fruit juice
Sponsors
MDS Pharma Services
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Written consents; * Adequate contraception from screening through 28 days after the last dose of study drug for female subjects; * Healthy obese or overweight subjects with BMI between 27 and 35.
Exclusion criteria
* History of glaucoma or any past or present use of medications to treat increased intraocular pressure; * Current use of any tobacco products, including cigarettes, cigars, pipes, or chewing tobacco, or use within the three months prior to screening; * History of drug abuse during the three years prior to screening; * History of alcohol abuse, or excessive alcohol consumption, or describes themselves as non-users of alcohol; * Current depression of moderate or greater severity, or any presence or history of suicidal behavior or active suicidal ideation * More than one lifetime episode of major depression; * Currently working night shifts at a job; * On average consumes greater than two cups of coffee or xanthine-containing beverages per day (\>200 mg/day) within the two weeks prior to screening; * Any use of dietary, herbal, and/or fitness/body-building supplements (with the exception of vitamins) within one month prior to screening; * Aspartate aminotransferase or alanine aminotransferase \>2.5 x ULN; * Serum creatinine ≥1.5 mg/dL for men or ≥1.4 mg/dL for women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | at breath alcohol levels 0.10%, 0.07%, and 0.04% | CogScreen-Psychomotor Edition (CogScreen-PM) consists of a series of computerized cognitive tasks, each self-contained and presented with instructions and a practice segment. The test battery takes about 20-25 minutes to perform. Performance on the test will be measured as the median reaction time for correct responses (PFNRTC) and coordination errors (PFNCOOR) before and after treatment. The measures of the tests are: (a) response speed, the median response time to complete each sequential step (PFNRTC); (b) response accuracy (PF Number Accuracy \[PFNACC\]); and (c) a coordination measure indicating the respondent's proximity to the center of the target numbers and letters (PF Number Coordination \[PFNCOOR\]). PF measures number sequencing skills, immediate memory, psychomotor speed and coordination, and visual scanning. The normal range for PFN scores is 1.17-2.16. Scores that are higher than this range indicate some level of psychomotor impairment. |
| Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 2 and Hour 6 | CogScreen-Psychomotor Edition (CogScreen-PM) consists of a series of computerized cognitive tasks, each self-contained and presented with instructions and a practice segment. The test battery takes about 20-25 minutes to perform. Performance on the test will be measured as the median reaction time for correct responses (PFNRTC) and coordination errors (PFNCOOR) before and after treatment. The measures of the tests are: (a) response speed, the median response time to complete each sequential step (PFNRTC); (b) response accuracy (PF Number Accuracy \[PFNACC\]); and (c) a coordination measure indicating the respondent's proximity to the center of the target numbers and letters (PF Number Coordination \[PFNCOOR\]). PF measures number sequencing skills, immediate memory, psychomotor speed and coordination, and visual scanning. The normal range for PFN scores is 1.17-2.16. Scores that are higher than this range indicate some level of psychomotor impairment. |
Countries
United States
Participant flow
Recruitment details
Subject recruitment occurred within the US between January 2009 and March 2009
Pre-assignment details
Period 1 was not a crossover design. Subjects were randomized to either alcohol or alcohol-placebo. Subjects who completed Period 1 were then randomized to the crossover portion of the study, Periods 2 and 3.
Participants by arm
| Arm | Count |
|---|---|
| Alcohol, VI-0521 Placebo Then VI-0521 Participants in this study arm were given alcohol in period 1, VI-0521 placebo in period 2 and VI-0521 in period 3. | 15 |
| Alcohol, VI-0521 Then VI-0521 Placebo Participants in this study arm were given alcohol in period 1, VI-0521 in period 2 and VI-0521-placebo in period 3. | 8 |
| Alcohol Placebo, VI-0521 Placebo Then VI-0521 Participants in this study arm were given alcohol placebo in period 1, VI-0521-placebo in period 2 and VI-0521 in period 3. | 8 |
| Alcohol Placebo, VI-0521 Then VI-0521 Placebo Participants in this study arm were given alcohol placebo in period 1, VI-0521 in period 2 and VI-0521 placebo in period 3. | 14 |
| Alcohol Only Subjects in this study arm only participated in period 1 and were given alcohol. | 18 |
| Alcohol Placebo Only Subject in this study arm only participated in period 1 and were given alcohol placebo. | 17 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 (1 Day) | Adverse Event | 0 | 0 | 0 | 0 | 3 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 2 | Need to take concomitant medication | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Protocol Violation | 1 | 0 | 1 | 0 | 0 | 0 |
| Period 2 | sponsor request | 0 | 0 | 1 | 1 | 0 | 0 |
| Period 3 | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3 | Protocol Violation | 0 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Alcohol, VI-0521 Placebo Then VI-0521 | Alcohol, VI-0521 Then VI-0521 Placebo | Alcohol Placebo, VI-0521 Placebo Then VI-0521 | Alcohol Placebo, VI-0521 Then VI-0521 Placebo | Alcohol Only | Alcohol Placebo Only | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 26.7 years STANDARD_DEVIATION 5.4 | 29.9 years STANDARD_DEVIATION 7.8 | 31.1 years STANDARD_DEVIATION 8.6 | 27.4 years STANDARD_DEVIATION 6.1 | 30.1 years STANDARD_DEVIATION 7.7 | 27.4 years STANDARD_DEVIATION 6.3 | 28.5 years STANDARD_DEVIATION 6.8 |
| Region of Enrollment United States | 15 participants | 8 participants | 8 participants | 14 participants | 18 participants | 17 participants | 80 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 1 Participants | 6 Participants | 7 Participants | 1 Participants | 21 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 7 Participants | 8 Participants | 11 Participants | 16 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 39 | 22 / 41 | 11 / 42 | 14 / 39 |
| serious Total, serious adverse events | 0 / 39 | 0 / 41 | 0 / 42 | 0 / 39 |
Outcome results
Primary
Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1.
CogScreen-Psychomotor Edition (CogScreen-PM) consists of a series of computerized cognitive tasks, each self-contained and presented with instructions and a practice segment. The test battery takes about 20-25 minutes to perform. Performance on the test will be measured as the median reaction time for correct responses (PFNRTC) and coordination errors (PFNCOOR) before and after treatment. The measures of the tests are: (a) response speed, the median response time to complete each sequential step (PFNRTC); (b) response accuracy (PF Number Accuracy \[PFNACC\]); and (c) a coordination measure indicating the respondent's proximity to the center of the target numbers and letters (PF Number Coordination \[PFNCOOR\]). PF measures number sequencing skills, immediate memory, psychomotor speed and coordination, and visual scanning. The normal range for PFN scores is 1.17-2.16. Scores that are higher than this range indicate some level of psychomotor impairment.
Time frame: at breath alcohol levels 0.10%, 0.07%, and 0.04%
Population: modified-intent-to-treat (mITT)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1 Alcohol-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.10% | 1.57 scores on a scale | Standard Error 0.06 |
| Period 1 Alcohol-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.07% | 1.67 scores on a scale | Standard Error 0.04 |
| Period 1 Alcohol-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.04% | 1.62 scores on a scale | Standard Error 0.05 |
| Period 1 Alcohol | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.10% | 1.90 scores on a scale | Standard Error 0.06 |
| Period 1 Alcohol | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.07% | 1.88 scores on a scale | Standard Error 0.05 |
| Period 1 Alcohol | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With Alcohol Compared to Alcohol Placebo in Period 1. | Breath Alcohol Level 0.04% | 1.68 scores on a scale | Standard Error 0.05 |
Comparison: at alcohol level 0.10%ANCOVA
Comparison: at alcohol level 0.07%ANCOVA
Comparison: at alcohol level 0.04%ANCOVA
Primary
Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3.
CogScreen-Psychomotor Edition (CogScreen-PM) consists of a series of computerized cognitive tasks, each self-contained and presented with instructions and a practice segment. The test battery takes about 20-25 minutes to perform. Performance on the test will be measured as the median reaction time for correct responses (PFNRTC) and coordination errors (PFNCOOR) before and after treatment. The measures of the tests are: (a) response speed, the median response time to complete each sequential step (PFNRTC); (b) response accuracy (PF Number Accuracy \[PFNACC\]); and (c) a coordination measure indicating the respondent's proximity to the center of the target numbers and letters (PF Number Coordination \[PFNCOOR\]). PF measures number sequencing skills, immediate memory, psychomotor speed and coordination, and visual scanning. The normal range for PFN scores is 1.17-2.16. Scores that are higher than this range indicate some level of psychomotor impairment.
Time frame: Hour 2 and Hour 6
Population: Intent-to-treat (ITT) ITT population includes participants who completed Periods 1, 2 and 3. Subjects that were discontinued due to adverse events, failed drug/alcohol screens, non-compliance, etc. are not included in this analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1 Alcohol-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 6 | 1.67 scores on a scale | Standard Error 0.04 |
| Period 1 Alcohol-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 2 | 1.69 scores on a scale | Standard Error 0.04 |
| Period 1 Alcohol | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 6 | 1.60 scores on a scale | Standard Error 0.04 |
| Period 1 Alcohol | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 2 | 1.64 scores on a scale | Standard Error 0.04 |
| Period 3 VI-0521-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 2 | 1.65 scores on a scale | Standard Error 0.04 |
| Period 3 VI-0521-placebo | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 6 | 1.65 scores on a scale | Standard Error 0.03 |
| Period 3 VI-0521 | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 6 | 1.60 scores on a scale | Standard Error 0.03 |
| Period 3 VI-0521 | Measure of Psychomotor Function Using Speed and Coordination on the CogScreen Pathfinder Number (PFN) Test in Subjects Treated With VI-0521 Compared to Placebo in Periods 2 and 3. | Hour 2 | 1.64 scores on a scale | Standard Error 0.04 |
Comparison: at 2 hr timepoint95% CI: [-0.17, 0.07]ANCOVA
Comparison: at 6 hr timepoint95% CI: [-0.18, 0.04]ANCOVA
Comparison: at 2 hr timepoint95% CI: [-0.08, 0.06]ANCOVA
Comparison: at 6 hr timepoint95% CI: [-0.13, 0.05]ANCOVA