Excessive Sleepiness, Obstructive Sleep Apnea
Conditions
Keywords
Driving
Brief summary
This trial is a randomized, double-blind, placebo-controlled, crossover study to evaluate the effect of JZP-110 on driving performance in subjects with excessive sleepiness due to obstructive sleep apnea.
Interventions
DRUGJZP-110
DRUGPlacebo
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, age 21 to 65 years inclusive 2. Diagnosis of obstructive sleep apnea (OSA) per International Classification of Sleep Disorders (ICSD-3) 3. BMI 18 to \<40 kg/m2 4. Willing and able to provide written informed consent
Exclusion criteria
1. Female subjects who are pregnant, nursing, or lactating 2. Any other clinically relevant medical, behavioral, or psychiatric disorder other than OSA that is associated with excessive sleepiness 3. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria 4. History or presence of any unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy and/or safety assessments per the judgment of the investigator 5. History of bariatric surgery within the past year or a history of any gastric bypass procedure 6. Presence or history of significant cardiovascular disease 7. Unable to washout or refrain from taking any over-the-counter (OTC) or prescription medications that could affect sleep-wake function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax) | 2 hours post-dose | Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | 2 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | 6 hours post-dose | Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| SDLP at 6 Hours Post-dose | 6 hours post-dose | Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns. |
| SDS at 6 Hours Post-dose | 6 hours post-dose | Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed. |
| Number of Lapses in Driving Test at 2 Hours Post-dose | 2 hours post-dose | Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study. |
| Number of Lapses in Driving Test at 6 Hours Post-dose | 6 hours post-dose | Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study. |
| Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose | 2 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec). |
| PVT Number of Lapses at 6 Hours Post-dose | 6 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec). |
| PVT Mean Reaction Time at 2 Hours Post-dose | 2 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured in msec. |
| PVT Mean Reaction Time at 6 Hours Post-dose | 6 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured In msec. |
| PVT Inverse Reaction Time at 2 Hours Post-dose | 2 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec. |
| PVT Inverse Reaction Time at 6 Hours Post-dose | 6 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec. |
| PVT Number of Errors of Commission at 2 Hours Post-dose | 2 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec). |
| PVT Number of Errors of Commission at 6 Hours Post-dose | 6 hours post-dose | The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec). |
| Toronto Hospital Alert Test (THAT) | Post Treatment at day 21 | THAT is a 10-item self-report questionnaire designed to measure perceived alertness in the preceding week. The THAT was administered at baseline and the end of each treatment period. The total score of THAT can range between 0 to 50 where the higher score indicates greater alertness. |
| Standard Deviation of Speed (SDS) at 2 Hours Post-dose | 2 hours post-dose | Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| JZP-110/Placebo JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or the matching placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order. | 17 |
| Placebo/JZP-110 Placebo for 7 days or JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) in Treatment Period 1 or Treatment Period 2 in a counterbalanced order. | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | JZP-110/Placebo | Total | Placebo/JZP-110 |
|---|---|---|---|
| Age, Continuous | 51.0 years STANDARD_DEVIATION 11.85 | 51.6 years STANDARD_DEVIATION 12.3 | 52.2 years STANDARD_DEVIATION 15.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 34 Participants | 17 Participants |
| Region of Enrollment Netherlands | 17 participants | 34 participants | 17 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 16 Participants | 30 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 34 |
| other Total, other adverse events | 8 / 33 | 15 / 34 |
| serious Total, serious adverse events | 0 / 33 | 0 / 34 |
Outcome results
Primary
Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax)
Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: One subject participated in only Treatment Period 1 and did not receive placebo resulting in 33 subjects in placebo group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax) | 19.92 centimeter (cm) | Standard Error 0.63 |
| JZP-110 | Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax) | 18.83 centimeter (cm) | Standard Error 0.627 |
p-value: 0.0062ANOVA
Secondary
Number of Lapses in Driving Test at 2 Hours Post-dose
Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.
Time frame: 2 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Lapses in Driving Test at 2 Hours Post-dose | 2.89 number of lapses | Standard Error 0.566 |
| JZP-110 | Number of Lapses in Driving Test at 2 Hours Post-dose | 1.76 number of lapses | Standard Error 0.558 |
p-value: 0.0806ANOVA
Secondary
Number of Lapses in Driving Test at 6 Hours Post-dose
Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.
Time frame: 6 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Lapses in Driving Test at 6 Hours Post-dose | 2.07 number of lapses | Standard Error 0.573 |
| JZP-110 | Number of Lapses in Driving Test at 6 Hours Post-dose | 2.12 number of lapses | Standard Error 0.573 |
p-value: 0.9391ANOVA
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 12 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 7 Participants |
p-value: 0.3593McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 13 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 5 Participants |
p-value: 0.0963McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 9 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 6 Participants |
p-value: 0.6072McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 15 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 5 Participants |
p-value: 0.0414McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 12 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 5 Participants |
p-value: 0.1435McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 8 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 6 Participants |
p-value: 0.7905McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 10 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 4 Participants |
p-value: 0.1796McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 5 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 5 Participants |
p-value: 1McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 8 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 2 Participants |
p-value: 0.1094McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 4 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 4 Participants |
p-value: 1McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 2 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Improved | 5 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose | Impaired | 2 Participants |
p-value: 0.4531McNemar
Secondary
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: The arms/group titles are combined as (solriamfetol minus placebo) for this outcome measure. Pre-specified McNemar test results were defined by driving study completion status per participant as impaired or improved (JZP-110 minus Placebo). The modified intent-to-treat (mITT) analysis population was comprised of all randomized subjects who received at least one dose of study medication and had evaluable SDLP data at 2 hours postdose in any post-baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Improved | 3 Participants |
| Placebo | Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose | Impaired | 4 Participants |
p-value: 1McNemar
Secondary
Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec).
Time frame: 2 hours post-dose
Population: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose | 6.37 lapses | Standard Error 2.111 |
| JZP-110 | Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose | 2.71 lapses | Standard Error 2.077 |
p-value: 0.2116ANOVA
Secondary
PVT Inverse Reaction Time at 2 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
Time frame: 2 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Inverse Reaction Time at 2 Hours Post-dose | 3.59 (1/RT(ms)) | Standard Error 0.111 |
| JZP-110 | PVT Inverse Reaction Time at 2 Hours Post-dose | 3.69 (1/RT(ms)) | Standard Error 0.11 |
p-value: 0.3426ANOVA
Secondary
PVT Inverse Reaction Time at 6 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
Time frame: 6 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Inverse Reaction Time at 6 Hours Post-dose | 3.59 (1/RT(ms)) | Standard Error 0.111 |
| JZP-110 | PVT Inverse Reaction Time at 6 Hours Post-dose | 3.75 (1/RT(ms)) | Standard Error 0.11 |
p-value: 0.1531ANOVA
Secondary
PVT Mean Reaction Time at 2 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured in msec.
Time frame: 2 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Mean Reaction Time at 2 Hours Post-dose | 318.66 msec | Standard Error 19.307 |
| JZP-110 | PVT Mean Reaction Time at 2 Hours Post-dose | 286.55 msec | Standard Error 19.004 |
p-value: 0.2144ANOVA
Secondary
PVT Mean Reaction Time at 6 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured In msec.
Time frame: 6 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Mean Reaction Time at 6 Hours Post-dose | 341.37 msec | Standard Error 19.307 |
| JZP-110 | PVT Mean Reaction Time at 6 Hours Post-dose | 286.88 msec | Standard Error 19.188 |
p-value: 0.0387ANOVA
Secondary
PVT Number of Errors of Commission at 2 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec).
Time frame: 2 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Number of Errors of Commission at 2 Hours Post-dose | 2.40 lapses | Standard Error 0.741 |
| JZP-110 | PVT Number of Errors of Commission at 2 Hours Post-dose | 1.82 lapses | Standard Error 0.73 |
p-value: 0.5603ANOVA
Secondary
PVT Number of Errors of Commission at 6 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec).
Time frame: 6 hours post-dose
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Number of Errors of Commission at 6 Hours Post-dose | 2.46 lapses | Standard Error 0.741 |
| JZP-110 | PVT Number of Errors of Commission at 6 Hours Post-dose | 1.76 lapses | Standard Error 0.74 |
p-value: 0.4851ANOVA
Secondary
PVT Number of Lapses at 6 Hours Post-dose
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec).
Time frame: 6 hours post-dose
Population: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PVT Number of Lapses at 6 Hours Post-dose | 7.73 lapses | Standard Error 2.111 |
| JZP-110 | PVT Number of Lapses at 6 Hours Post-dose | 3.60 lapses | Standard Error 2.086 |
p-value: 0.1604ANOVA
Secondary
SDLP at 6 Hours Post-dose
Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
Time frame: 6 hours post-dose
Population: Subjects in the modified intent-to-treat (mITT) population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | SDLP at 6 Hours Post-dose | 20.04 cm | Standard Error 0.632 |
| JZP-110 | SDLP at 6 Hours Post-dose | 19.24 cm | Standard Error 0.631 |
p-value: 0.0432ANOVA
Secondary
SDS at 6 Hours Post-dose
Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed.
Time frame: 6 hours post-dose
Population: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | SDS at 6 Hours Post-dose | 2.84 km/hr | Standard Error 0.1 |
| JZP-110 | SDS at 6 Hours Post-dose | 2.73 km/hr | Standard Error 0.099 |
p-value: 0.1991ANOVA
Secondary
Standard Deviation of Speed (SDS) at 2 Hours Post-dose
Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed.
Time frame: 2 hours post-dose
Population: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Standard Deviation of Speed (SDS) at 2 Hours Post-dose | 2.55 kilometers/hour (km/hr) | Standard Error 0.099 |
| JZP-110 | Standard Deviation of Speed (SDS) at 2 Hours Post-dose | 2.62 kilometers/hour (km/hr) | Standard Error 0.098 |
p-value: 0.4116ANOVA
Secondary
Toronto Hospital Alert Test (THAT)
THAT is a 10-item self-report questionnaire designed to measure perceived alertness in the preceding week. The THAT was administered at baseline and the end of each treatment period. The total score of THAT can range between 0 to 50 where the higher score indicates greater alertness.
Time frame: Post Treatment at day 21
Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Toronto Hospital Alert Test (THAT) | 23.94 score on a scale | Standard Error 1.18 |
| JZP-110 | Toronto Hospital Alert Test (THAT) | 27.52 score on a scale | Standard Error 1.162 |
p-value: 0.0241ANOVA