Epilepsy
Conditions
Keywords
Perampanel, Cognition
Brief summary
The objective of this study is to determine whether there are any differences in the cognitive abilities and/or behavioral response of normal healthy volunteers across different titration rates of perampanel.
Detailed description
This is a randomized, double-blind, parallel group design across different titration rates of perampanel in healthy volunteers. The study consists of 8 visits, 4 of which will occur at the participant's home, over a 7-week period. One hundred and three (103) normal healthy subjects will be treated with perampanel (PER) at one of four different titration rates: (1) 2mg/day PER for one week followed by 4mg/day PER for five weeks, (2) 2mg/day PER for two weeks followed by 4mg/day PER for four weeks, (3) 4mg/day PER for six weeks, or (4) placebo (0mg/day PER) for six weeks. Cognitive and behavioral function testing along with safety testing will be conducted at screening, pretreatment baseline, the end of each week during the titration and maintenance period.
Interventions
DRUGPerampanel 1 week titration
Healthy adults will take 2mg perampanel PO QD for one week followed 4mg perampanel PO QD for five weeks.
DRUGPerampanel 2 week titration
Healthy adults will take 2mg perampanel PO QD for two weeks followed 4mg perampanel PO QD for four weeks.
DRUGPerampanel 4mg
Healthy adults will take 4mg perampanel PO QD for six weeks
DRUGPlacebo
Healthy adults will take 2mg placebo PO QD for six weeks
Sponsors
Eisai Inc.
Kimford Jay Meador
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adults between the ages of 18 and 55 years 2. Male or female (using approved birth control methods) 3. Informed consent obtained
Exclusion criteria
1. Presence of clinically significant cardiovascular, endocrine, hematopoietic, hepatic, neurologic, psychiatric, or renal disease. 2. Presence or history of drug or alcohol abuse or positive urine drug test at screening. 3. The use of concomitant medications, which are known to affect perampanel or the use of any concomitant medications that may alter cognitive function (see Section VIII.F for a partial list). 4. Prior adverse reaction to or prior hypersensitivity to perampanel. 5. Prior participation in studies involving perampanel. 6. Subjects who have received any investigational drug within the previous thirty days. 7. Subjects with IQ \< 80 as determined by the Peabody Picture Vocabulary Test after enrollment. 8. Positive pregnancy test. Women of childbearing potential will be required to use approved birth control methods during the study. 9. Presence of lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the C-SSRS at Screening. 10. Invalid results on computerized cognitive tests at screening as indicated by a 'No' on any of the validity indicators generated in the CNS Vital Signs report.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | At the end of each week of treatment for 6 weeks. | Z score of cognitive tests (selected performance measures from the computerized cognitive test battery) and questionnaires (AEP, POMS, QOLIE-cognitive questions) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) Executive Function Score of computerized test battery; 2) Processing Speed Score of computerized test battery; 3) AEP total score; 4) POMS total and domain scores; 5) Three cognitive components of the QOLIE-31 (attention, memory, language). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. |
| Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | At the end of each week of treatment for 6 weeks. | Z score of objective cognitive tests (selected performance measures from the computerized cognitive test battery) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. |
| Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | At the end of each week of treatment for 6 weeks. | Z score of subjective questionnaires (AEP, POMS, QOLIE-cognitive questions at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) AEP total score; 2) POMS total and domain scores; 3) Three cognitive components of the QOLIE-31 (attention, memory, language). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | At the end of each week of treatment for 6 weeks. | Number of TEAEs across the the four titration conditions over the six-week treatment period. A score of 0 indicates no TEAEs. Higher numbers indicate greater TEAEs. |
| Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | At the end of each week of treatment for 6 weeks. | Number dropouts across the the four titration conditions over the six-week treatment period. A score of 0 indicates no dropouts. Higher numbers indicate greater dropouts. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants take 2mg placebo PO QD for six weeks. | 4 |
| PER 1 Week Titration Participants take 2mg perampanel PO QD for one week and 4mg perampanel PO QD for five weeks. | 7 |
| PER 2 Week Titration Participants take 2mg perampanel PO QD for two weeks and 4mg perampanel PO QD for four weeks. | 7 |
| PER 4 mg Participants take 4mg perampanel PO QD for six weeks | 11 |
| Total | 29 |
Baseline characteristics
| Characteristic | PER 1 Week Titration | PER 2 Week Titration | Placebo | PER 4 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 34.7 Years STANDARD_DEVIATION 10.3 | 30.3 Years STANDARD_DEVIATION 8.9 | 44.8 Years STANDARD_DEVIATION 10.3 | 39.7 Years STANDARD_DEVIATION 12.8 | 36.9 Years STANDARD_DEVIATION 11.6 |
| Education Level | 17 Years STANDARD_DEVIATION 1.9 | 16 Years STANDARD_DEVIATION 1.2 | 16 Years STANDARD_DEVIATION 1.6 | 15.7 Years STANDARD_DEVIATION 2.2 | 16.1 Years STANDARD_DEVIATION 1.8 |
| IQ Estimate | 102.3 units on a scale STANDARD_DEVIATION 6.7 | 97.1 units on a scale STANDARD_DEVIATION 11 | 99 units on a scale STANDARD_DEVIATION 7.1 | 102.9 units on a scale STANDARD_DEVIATION 7.4 | 100.8 units on a scale STANDARD_DEVIATION 8.2 |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian | 4 Participants | 1 Participants | 2 Participants | 6 Participants | 13 Participants |
| Region of Enrollment United States | 7 participants | 7 participants | 4 participants | 11 participants | 29 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 1 Participants | 6 Participants | 13 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 | 0 / 2 | 0 / 3 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 1 / 2 | 2 / 3 | 5 / 6 | 7 / 8 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Z score of objective cognitive tests (selected performance measures from the computerized cognitive test battery) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean.
Time frame: At the end of each week of treatment for 6 weeks.
Population: Participants who completed the protocol are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | -.69 score on a scale | Standard Deviation 0.52 |
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | .06 score on a scale | Standard Deviation 0.19 |
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | .26 score on a scale | Standard Deviation 0.03 |
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | .28 score on a scale | Standard Deviation 0.25 |
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .04 score on a scale | Standard Deviation 0.3 |
| Placebo | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .51 score on a scale | Standard Deviation 0.15 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .24 score on a scale | Standard Deviation 0.3 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | .33 score on a scale | Standard Deviation 0.02 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .61 score on a scale | Standard Deviation 0.21 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .28 score on a scale | Standard Deviation 0.23 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | .11 score on a scale | Standard Deviation 0.38 |
| PER 1 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | .44 score on a scale | Standard Deviation 0.2 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .05 score on a scale | Standard Deviation 0.12 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .04 score on a scale | Standard Deviation 0.38 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.05 score on a scale | Standard Deviation 0.02 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | -.17 score on a scale | Standard Deviation 0.38 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.15 score on a scale | Standard Deviation 0.01 |
| PER 2 Week Titration | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.21 score on a scale | Standard Deviation 0.34 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.06 score on a scale | Standard Deviation 0.37 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | .07 score on a scale | Standard Deviation 0.08 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | .11 score on a scale | Standard Deviation 0.4 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .11 score on a scale | Standard Deviation 0.23 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .27 score on a scale | Standard Deviation 0.31 |
| PER 4 mg | Composite Z-score of Objective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .11 score on a scale | Standard Deviation 0.11 |
Primary
Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Z score of subjective questionnaires (AEP, POMS, QOLIE-cognitive questions at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) AEP total score; 2) POMS total and domain scores; 3) Three cognitive components of the QOLIE-31 (attention, memory, language). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean.
Time frame: At the end of each week of treatment for 6 weeks.
Population: Participants who completed the protocol are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | -.36 score on a scale | Standard Deviation 1.08 |
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.35 score on a scale | Standard Deviation 0.96 |
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | -.28 score on a scale | Standard Deviation 0.89 |
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | -.47 score on a scale | Standard Deviation 0.79 |
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.41 score on a scale | Standard Deviation 0.91 |
| Placebo | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.69 score on a scale | Standard Deviation 0.93 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.14 score on a scale | Standard Deviation 0.49 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | -.12 score on a scale | Standard Deviation 0.4 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | -.20 score on a scale | Standard Deviation 0.5 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | -.23 score on a scale | Standard Deviation 0.28 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.09 score on a scale | Standard Deviation 0.43 |
| PER 1 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.19 score on a scale | Standard Deviation 0.54 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.17 score on a scale | Standard Deviation 0.28 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .04 score on a scale | Standard Deviation 0.44 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .14 score on a scale | Standard Deviation 0.51 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.03 score on a scale | Standard Deviation 0.36 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.01 score on a scale | Standard Deviation 0.38 |
| PER 2 Week Titration | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .05 score on a scale | Standard Deviation 0.28 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | .42 score on a scale | Standard Deviation 0.43 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | .41 score on a scale | Standard Deviation 0.45 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | .16 score on a scale | Standard Deviation 0.27 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .27 score on a scale | Standard Deviation 0.32 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .36 score on a scale | Standard Deviation 0.34 |
| PER 4 mg | Composite Z-score of Subjective Measures as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .28 score on a scale | Standard Deviation 0.26 |
Primary
Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Z score of cognitive tests (selected performance measures from the computerized cognitive test battery) and questionnaires (AEP, POMS, QOLIE-cognitive questions) at the end of each week of drug treatment for each titration arm, controlling for baseline measures collected prior to treatment. Various measures were combined collectively (averaged) to compute an overall Z-score for each group at each time point. These included: 1) Executive Function Score of computerized test battery; 2) Processing Speed Score of computerized test battery; 3) AEP total score; 4) POMS total and domain scores; 5) Three cognitive components of the QOLIE-31 (attention, memory, language). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poorer performance compared to the mean and positive numbers represent higher performance compared to the mean.
Time frame: At the end of each week of treatment for 6 weeks.
Population: Participants who completed the protocol are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | -.41 score on a scale | Standard Deviation 1 |
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.25 score on a scale | Standard Deviation 0.9 |
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | -.14 score on a scale | Standard Deviation 0.71 |
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | -.32 score on a scale | Standard Deviation 0.81 |
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.34 score on a scale | Standard Deviation 0.85 |
| Placebo | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.28 score on a scale | Standard Deviation 0.87 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.03 score on a scale | Standard Deviation 0.45 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | -.06 score on a scale | Standard Deviation 0.4 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | -.07 score on a scale | Standard Deviation 0.55 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | -.03 score on a scale | Standard Deviation 0.36 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.01 score on a scale | Standard Deviation 0.44 |
| PER 1 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.11 score on a scale | Standard Deviation 0.53 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | -.15 score on a scale | Standard Deviation 0.26 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .02 score on a scale | Standard Deviation 0.34 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .09 score on a scale | Standard Deviation 0.49 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | -.11 score on a scale | Standard Deviation 0.35 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | -.03 score on a scale | Standard Deviation 0.35 |
| PER 2 Week Titration | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .05 score on a scale | Standard Deviation 0.28 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 5 | .37 score on a scale | Standard Deviation 0.41 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 6 | .21 score on a scale | Standard Deviation 0.48 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 2 | .15 score on a scale | Standard Deviation 0.27 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 4 | .23 score on a scale | Standard Deviation 0.33 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 1 | .32 score on a scale | Standard Deviation 0.33 |
| PER 4 mg | Overall Neuropsychological Composite Z-score as a Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | Week 3 | .10 score on a scale | Standard Deviation 0.34 |
Secondary
Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Number dropouts across the the four titration conditions over the six-week treatment period. A score of 0 indicates no dropouts. Higher numbers indicate greater dropouts.
Time frame: At the end of each week of treatment for 6 weeks.
Population: All participants included in analysis. However, zero participants withdrew from the study after starting the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 0 Participants |
| PER 1 Week Titration | Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 0 Participants |
| PER 2 Week Titration | Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 0 Participants |
| PER 4 mg | Dropouts Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 0 Participants |
Secondary
Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment.
Number of TEAEs across the the four titration conditions over the six-week treatment period. A score of 0 indicates no TEAEs. Higher numbers indicate greater TEAEs.
Time frame: At the end of each week of treatment for 6 weeks.
Population: All participants who completed the protocol are included in the analysis. However, zero participants withdrew from the study after starting the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 5 TEAEs |
| PER 1 Week Titration | Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 9 TEAEs |
| PER 2 Week Titration | Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 9 TEAEs |
| PER 4 mg | Treatment Emergent Adverse Events (TEAEs) Across the Six-week Treatment Period Measure of Direct Comparison of the 4 Titration Conditions Across 6 Weeks of Treatment. | 11 TEAEs |