Study Assessing Effects of JZP-110 on Driving Performance in the Treatment of Excessive Sleepiness in Narcolepsy

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02806908
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 35.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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 narcolepsy.

Condition or Disease	Intervention/Treatment	Phase
Narcolepsy; Excessive Sleepiness	Drug: JZP-110; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Narcolepsy
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: May 19, 2019
• Actual Study Completion Date: May 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Once daily dosing	Drug: Placebo
Active Comparator: JZP-110 150 mg/day for first 3 days and 300 mg/day for next 4 days	Drug: JZP-110; Other Names: solriamfetol

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. Number of Subjects With Improved or Impaired Driving at a Threshold 1 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Number of Lapses in Driving Test at 2 Hours Post-dose [2 hours post-dose]

    Number of driving lapses (also known as lane drift, was 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.

17. Number of Lapses in Driving Test at 6 Hours Post-dose [6 hours post-dose]

    Number of driving lapses (also known as lane drift, was 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.

18. 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 predose 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).

19. PVT Number of Lapses at 6 Hours Post-dose [6 hours post-dose]

    The PVT was administered at screening for practice only, and at predose 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).

20. PVT Mean Reaction Time at 2 Hours Post-dose [2 hours post-dose]

    The PVT was administered at screening for practice only, and at predose 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.

21. PVT Mean Reaction Time at 6 Hours Post-dose [6 hours post-dose]

    The PVT was administered at screening for practice only, and at predose 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.

22. PVT Inverse Reaction Time at 2 Hours Post-dose [2 hours post-dose]

    The PVT was administered at screening for practice only, and at predose 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.

23. PVT Inverse Reaction Time at 6 Hours Post-dose [6 hours post-dose]

    The PVT was administered at screening for practice only, and at predose 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.

24. 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 predose 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).

25. 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 predose 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).

26. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female, age 21 to 65 years inclusive

2. Diagnosis of narcolepsy per International Classification of Sleep Disorders (ICSD-3) or Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5)

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. Moderate or severe sleep apnea

3. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness

4. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria

5. 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

6. History of bariatric surgery within the past year or a history of any gastric bypass procedure

7. Presence or history of significant cardiovascular disease

8. Unable to washout or refrain from taking any over-the-counter (OTC) or prescription medications that could affect sleep-wake function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht University	Maastricht	Limburg	Netherlands	6229

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Study Director: Grace Wang, MD, Jazz Pharmaceuticals
• Principal Investigator: Jan Ramaekers, PhD, Maastricht University

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 9, 2019
• Study Protocol - Feb 7, 2018

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02806908
• Other Study ID Numbers: 15-005
• First Posted: Jun 21, 2016
• Last Update Posted: Jan 13, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Jazz Pharmaceuticals: Driving
• Additional relevant MeSH terms: Narcolepsy; Disorders of Excessive Somnolence; Sleepiness

Study Results

Participant Flow

Arm/Group Title	Placebo/JZP-110	JZP-110/Placebo
Arm/Group Description	Subjects received Placebo for 7 days or JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) in a counterbalanced order between Treatment Period 1 and Treatment Period 2.	Subjects received JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or the matching placebo for 7 days in a counterbalanced order between Treatment Period 1 and Treatment Period 2.
Period Title: Overall Study
STARTED	11	13
COMPLETED	10	12
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo/JZP-110	JZP-110/Placebo	Total
Arm/Group Description	Subjects received Placebo for 7 days or JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) in a counterbalanced order between Treatment Period 1 and Treatment Period 2.	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.	Total of all reporting groups
Overall Participants	11	13	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.2 (10.81)	41.4 (13.00)	40.4 (11.84)
Sex: Female, Male (Count of Participants)
Female	5 45.5%	6 46.2%	11 45.8%
Male	6 54.5%	7 53.8%	13 54.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 18.2%	0 0%	2 8.3%
White	9 81.8%	12 92.3%	21 87.5%
More than one race	0 0%	1 7.7%	1 4.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Netherlands	11 100%	13 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax)
Description	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

Outcome Measure Data

Analysis Population Description

The modified intent to treat (mITT) population consisted of 22 subjects.

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Median (Full Range) [centimeter (cm)]	20.46	19.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	SDLP at 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	21	22
Median (Full Range) [cm]	19.78	19.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0416
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	5 45.5%
Impaired	5 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0963
	Comments
	Method	McNemar
	Comments

4. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	10 90.9%
Impaired	5 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3018
	Comments
	Method	McNemar
	Comments

5. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	9 81.8%
Impaired	5 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4240
	Comments
	Method	McNemar
	Comments

6. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	6 54.5%
Impaired	4 36.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7539
	Comments
	Method	McNemar
	Comments

7. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	6 54.5%
Impaired	4 36.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7539
	Comments
	Method	McNemar
	Comments

8. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	4 36.4%
Impaired	4 36.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	McNemar
	Comments

9. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 1 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	10 90.9%
Impaired	7 63.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6291
	Comments
	Method	McNemar
	Comments

10. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	8 72.7%
Impaired	7 63.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	McNemar
	Comments

11. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	8 72.7%
Impaired	7 63.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	McNemar
	Comments

12. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	8 72.7%
Impaired	7 63.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	McNemar
	Comments

13. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	7 63.6%
Impaired	5 45.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7744
	Comments
	Method	McNemar
	Comments

14. Secondary Outcome

Title	Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Difference (JZP-110 -Placebo)
Arm/Group Description	JZP-110 - Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order. Placebo - Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22
Improved	6 54.5%
Impaired	6 54.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7539
	Comments
	Method	McNemar
	Comments

15. Secondary Outcome

Title	Standard Deviation of Speed (SDS) at 2 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [kilometers/hour (km/hr)]	2.97 (0.151)	2.76 (0.151)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1141
	Comments
	Method	ANOVA
	Comments

16. Secondary Outcome

Title	SDS at 6 Hours Post-dose
Description	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

Outcome Measure Data

Analysis Population Description

Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	21	22
Least Squares Mean (Standard Error) [km/hr]	3.18 (0.153)	3.08 (0.151)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4441
	Comments
	Method	ANOVA
	Comments

17. Secondary Outcome

Title	Number of Lapses in Driving Test at 2 Hours Post-dose
Description	Number of driving lapses (also known as lane drift, was 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [number of lapses]	3.26 (0.834)	2.27 (0.834)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3423
	Comments
	Method	ANOVA
	Comments

18. Secondary Outcome

Title	Number of Lapses in Driving Test at 6 Hours Post-dose
Description	Number of driving lapses (also known as lane drift, was 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

Outcome Measure Data

Analysis Population Description

Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	21	22
Least Squares Mean (Standard Error) [number of lapses]	3.72 (0.844)	3.64 (0.834)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9384
	Comments
	Method	ANOVA
	Comments

19. Secondary Outcome

Title	Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [lapses]	7.47 (2.357)	3.04 (2.357)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0939
	Comments
	Method	ANOVA
	Comments

20. Secondary Outcome

Title	PVT Number of Lapses at 6 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [lapses]	9.88 (2.357)	3.81 (2.357)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0246
	Comments
	Method	ANOVA
	Comments

21. Secondary Outcome

Title	PVT Mean Reaction Time at 2 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [msec]	633.30 (162.286)	311.74 (162.286)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1475
	Comments
	Method	ANOVA
	Comments

22. Secondary Outcome

Title	PVT Mean Reaction Time at 6 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [msec]	628.26 (162.286)	309.81 (162.286)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1513
	Comments
	Method	ANOVA
	Comments

23. Secondary Outcome

Title	PVT Inverse Reaction Time at 2 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [1/RT(ms))]	3.36 (0.136)	3.82 (0.136)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANOVA
	Comments

24. Secondary Outcome

Title	PVT Inverse Reaction Time at 6 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [1/RT(ms))]	3.34 (0.136)	3.77 (0.136)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANOVA
	Comments

25. Secondary Outcome

Title	PVT Number of Errors of Commission at 2 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [errors]	1.65 (0.439)	1.26 (0.439)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4774
	Comments
	Method	ANOVA
	Comments

26. Secondary Outcome

Title	PVT Number of Errors of Commission at 6 Hours Post-dose
Description	The PVT was administered at screening for practice only, and at predose 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [errors]	1.92 (0.439)	1.45 (0.439)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3801
	Comments
	Method	ANOVA
	Comments

27. Secondary Outcome

Title	Toronto Hospital Alert Test (THAT)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.	Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days) during Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Measure Participants	22	22
Least Squares Mean (Standard Error) [score on a scale]	26.83 (1.400)	33.97 (1.397)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, JZP-110
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days.
Adverse Event Reporting Description	The Safety Population consisted of all subjects who received at least 1 dose of study medication. A treatment-emergent AE (TEAE), was defined as an AE that either began after first study drug dose or worsened after the first dose. When determining the percent of subjects who experienced an AE, multiple increases in severity were counted as one AE.
Arm/Group Title	Placebo		JZP-110
Arm/Group Description	Subjects received a single oral daily dose of placebo for 7 days.		Subjects received a single oral daily dose of JZP-110 (150 mg/day for 3 days) then JZP-110 (300 mg/day for 4 days)
All Cause Mortality
	Placebo		JZP-110
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Serious Adverse Events
	Placebo		JZP-110
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		JZP-110
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)		17/23 (73.9%)
Cardiac disorders
Palpitations	0/23 (0%)	0	2/23 (8.7%)	2
Gastrointestinal disorders
Nausea	1/23 (4.3%)	1	2/23 (8.7%)	2
Metabolism and nutrition disorders
Decreased appetite	1/23 (4.3%)	1	4/23 (17.4%)	4
Nervous system disorders
Headache	3/23 (13%)	3	4/23 (17.4%)	4
Somnolence	2/23 (8.7%)	2	3/23 (13%)	3
Sleep disorder	1/23 (4.3%)	1	3/23 (13%)	3
Psychiatric disorders
Agitation	0/23 (0%)	0	3/23 (13%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.