Trial Outcomes & Findings for Study Assessing Effects of JZP-110 on Driving Performance in the Treatment of Excessive Sleepiness in Narcolepsy (NCT NCT02806908)

NCT ID: NCT02806908

Last Updated: 2021-01-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: 2 hours post-dose
• Results posted on: 2021-01-13

Participant Flow

Participant milestones

Measure	Placebo/JZP-110 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/Placebo 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.
Overall Study STARTED	11	13
Overall Study COMPLETED	10	12
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo/JZP-110 n=11 Participants 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/Placebo n=13 Participants 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 n=24 Participants Total of all reporting groups
Age, Continuous	39.2 years STANDARD_DEVIATION 10.81 • n=5 Participants	41.4 years STANDARD_DEVIATION 13.00 • n=7 Participants	40.4 years STANDARD_DEVIATION 11.84 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Netherlands	11 participants n=5 Participants	13 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours post-dose

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

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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax)	19.08 centimeter (cm) Interval 13.2 to 25.0	20.46 centimeter (cm) Interval 14.4 to 28.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=21 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
SDLP at 6 Hours Post-dose	19.59 cm Interval 13.0 to 26.9	19.78 cm Interval 14.6 to 38.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	5 Participants
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	10 Participants
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	9 Participants
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	6 Participants
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	6 Participants
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	—	4 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	4 Participants
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	—	4 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Number of Subjects With Improved or Impaired Driving at a Threshold 1 cm on JZP-110 Compared to Placebo 6 Hours Post-dose Improved	—	10 Participants
Number of Subjects With Improved or Impaired Driving at a Threshold 1 cm on JZP-110 Compared to Placebo 6 Hours Post-dose Impaired	—	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	8 Participants
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	—	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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
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	—	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	8 Participants
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	—	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	7 Participants
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	—	5 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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	—	6 Participants
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	—	6 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Standard Deviation of Speed (SDS) at 2 Hours Post-dose	2.76 kilometers/hour (km/hr) Standard Error 0.151	2.97 kilometers/hour (km/hr) Standard Error 0.151

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=21 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
SDS at 6 Hours Post-dose	3.08 km/hr Standard Error 0.151	3.18 km/hr Standard Error 0.153

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Number of Lapses in Driving Test at 2 Hours Post-dose	2.27 number of lapses Standard Error 0.834	3.26 number of lapses Standard Error 0.834

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=21 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Number of Lapses in Driving Test at 6 Hours Post-dose	3.64 number of lapses Standard Error 0.834	3.72 number of lapses Standard Error 0.844

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose	3.04 lapses Standard Error 2.357	7.47 lapses Standard Error 2.357

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Number of Lapses at 6 Hours Post-dose	3.81 lapses Standard Error 2.357	9.88 lapses Standard Error 2.357

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Mean Reaction Time at 2 Hours Post-dose	311.74 msec Standard Error 162.286	633.30 msec Standard Error 162.286

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Mean Reaction Time at 6 Hours Post-dose	309.81 msec Standard Error 162.286	628.26 msec Standard Error 162.286

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Inverse Reaction Time at 2 Hours Post-dose	3.82 1/RT(ms)) Standard Error 0.136	3.36 1/RT(ms)) Standard Error 0.136

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Inverse Reaction Time at 6 Hours Post-dose	3.77 1/RT(ms)) Standard Error 0.136	3.34 1/RT(ms)) Standard Error 0.136

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Number of Errors of Commission at 2 Hours Post-dose	1.26 errors Standard Error 0.439	1.65 errors Standard Error 0.439

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
PVT Number of Errors of Commission at 6 Hours Post-dose	1.45 errors Standard Error 0.439	1.92 errors Standard Error 0.439

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	JZP-110 n=22 Participants 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 n=22 Participants Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
Toronto Hospital Alert Test (THAT)	33.97 score on a scale Standard Error 1.397	26.83 score on a scale Standard Error 1.400

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

JZP-110

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=23 participants at risk Subjects received a single oral daily dose of placebo for 7 days.	JZP-110 n=23 participants at risk 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)
Cardiac disorders Palpitations	0.00% 0/23 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	8.7% 2/23 • Number of events 2 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Nervous system disorders Headache	13.0% 3/23 • Number of events 3 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	17.4% 4/23 • Number of events 4 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Nervous system disorders Somnolence	8.7% 2/23 • Number of events 2 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	13.0% 3/23 • Number of events 3 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Nervous system disorders Sleep disorder	4.3% 1/23 • Number of events 1 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	13.0% 3/23 • Number of events 3 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Gastrointestinal disorders Nausea	4.3% 1/23 • Number of events 1 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	8.7% 2/23 • Number of events 2 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Psychiatric disorders Agitation	0.00% 0/23 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	13.0% 3/23 • Number of events 3 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.
Metabolism and nutrition disorders Decreased appetite	4.3% 1/23 • Number of events 1 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.	17.4% 4/23 • Number of events 4 • Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination, up to 21 days. 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.

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 2158709177

Email: ClinicalTrialDisclosure@JazzPharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER