Healthy
Conditions
Keywords
Sleeplessness
Brief summary
This study will examine the next-day residual effects of a nighttime dose of gabapentin 250 mg, diphenhydramine citrate 76 mg and triazolam 0.5 mg compared to placebo and each other on simulated driving performance in normal volunteer subjects. It will also examine other measures of next-day performance and next-day sleepiness.
Interventions
DRUGGabapentin
250 mg, oral, prior to bedtime on the night before performance testing
DRUGDiphenhydramine citrate
76 mg, oral, prior to bedtime on the night before performance testing
DRUGTriazolam
0.5 mg, oral, prior to bedtime on the night before performance testing
DRUGPlacebo
Oral, prior to bedtime on the night before performance testing
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males and females of non-childbearing potential, 25-55 years of age * Valid driver's license
Exclusion criteria
* Psychiatric disorder * Recent history of clinically significant neurological disorder, such as seizures, stroke, multiple sclerosis, or head trauma * Recent histroy or current treatment for sleep disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standard Deviation of Lateral Position (SDLP) | 7.25 hours post-dose | Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). SDLP was used to assess driver's ability to track their lane and was the standard deviation of lane positions through the entire drive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Speed Deviation | 7.25 hours post dose | Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Standard deviation of speed was reported in the outcome measure. |
| Lane Exceedance | 7.25 hours post-dose | Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Mean lanes excursed/exceeded was reported in the outcome measure. |
Countries
United States
Participant flow
Pre-assignment details
Prior to randomization, all participants were screened for simulator sickness and underwent standardized training on the driving simulator to ensure that participants fully understood how to perform the tests, were comfortable, and attained a stable level of performance on the various performance-based measures.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants randomized to receive diphenhydramine citrate first, gabapentin first, triazolam first or placebo first. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Washout Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 1 |
| Washout Period 2 | Adverse Event | 0 | 0 | 0 | 1 |
| Washout Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 46 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 | 3 / 58 | 2 / 55 | 3 / 57 | 10 / 56 |
| serious Total, serious adverse events | 0 / 58 | 0 / 55 | 0 / 57 | 0 / 56 |
Outcome results
Primary
Standard Deviation of Lateral Position (SDLP)
Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). SDLP was used to assess driver's ability to track their lane and was the standard deviation of lane positions through the entire drive.
Time frame: 7.25 hours post-dose
Population: ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Standard Deviation of Lateral Position (SDLP) | 33.2 centimeter (cm) | Standard Deviation 8 |
| Gabapentin | Standard Deviation of Lateral Position (SDLP) | 34.2 centimeter (cm) | Standard Deviation 10 |
| Diphenhydramine Citrate | Standard Deviation of Lateral Position (SDLP) | 35.4 centimeter (cm) | Standard Deviation 8.9 |
| Triazolam | Standard Deviation of Lateral Position (SDLP) | 47.4 centimeter (cm) | Standard Deviation 12 |
Comparison: For primary endpoint sequential order of testing: triazolam versus (vs) placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: <0.00195% CI: [10.85, 17.4]Wilcoxon Rank Sum test
Comparison: For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.95% CI: [-0.66, 2.33]
Comparison: For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: 0.13495% CI: [-0.39, 2.51]Wilcoxon Rank Sum test
Comparison: For primary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: <0.00195% CI: [1.01, 3.98]Wilcoxon Rank Sum test
Secondary
Lane Exceedance
Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Mean lanes excursed/exceeded was reported in the outcome measure.
Time frame: 7.25 hours post-dose
Population: ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lane Exceedance | 37.8 lanes exceeded | Standard Deviation 45.9 |
| Gabapentin | Lane Exceedance | 46.7 lanes exceeded | Standard Deviation 58.5 |
| Diphenhydramine Citrate | Lane Exceedance | 52.4 lanes exceeded | Standard Deviation 62 |
| Triazolam | Lane Exceedance | 147.7 lanes exceeded | Standard Deviation 113.6 |
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: <0.00195% CI: [72, 130.5]Wilcoxon Rank Sum test
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.95% CI: [-4, 16.5]
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: 0.21395% CI: [-3, 9]Wilcoxon Rank Sum test
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: 0.00395% CI: [4, 20.5]Wilcoxon Rank Sum test
Secondary
Speed Deviation
Driving performance assessment for the participants were measured by simulated driving test using Cognitive Research Corporation Driving Simulator (CRCDS-MiniSim). The assessment was performed after 45 minutes of awakening from approximately 6.5 hours of sleep on testing day (after 7.25 hours of study drug administration). Standard deviation of speed was reported in the outcome measure.
Time frame: 7.25 hours post dose
Population: ITT population included all randomized participants who received at least 1 dose of investigational product and provided any data post-randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Speed Deviation | 0.9 meters per second (m/sec) | Standard Deviation 0.3 |
| Gabapentin | Speed Deviation | 0.9 meters per second (m/sec) | Standard Deviation 0.3 |
| Diphenhydramine Citrate | Speed Deviation | 1.0 meters per second (m/sec) | Standard Deviation 0.3 |
| Triazolam | Speed Deviation | 1.3 meters per second (m/sec) | Standard Deviation 0.6 |
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: <0.00195% CI: [0.26, 0.47]Wilcoxon Rank Sum test
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.95% CI: [-0.07, 0.05]
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: 0.01295% CI: [0.02, 0.12]Wilcoxon Rank Sum test
Comparison: For secondary endpoint sequential order of testing: triazolam vs placebo; gabapentin vs placebo; diphenhydramine citrate vs gabapentin; diphenhydramine citrate vs placebo. If comparison at preceding step was significant, only then subsequent comparisons were considered significant.p-value: 0.01495% CI: [0.01, 0.12]Wilcoxon Rank Sum test