Trial Outcomes & Findings for Study Assessing Effects of JZP-110 on Driving Performance in the Treatment of Excessive Sleepiness in OSA (NCT NCT02806895)
NCT ID: NCT02806895
Last Updated: 2021-01-14
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.
COMPLETED
PHASE2
34 participants
2 hours post-dose
2021-01-14
Participant Flow
Participant milestones
| Measure |
(Treatment Period 1) 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.
|
(Treatment Period 2) 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.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
COMPLETED
|
16
|
17
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
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 OSA
Baseline characteristics by cohort
| Measure |
JZP-110/Placebo
n=17 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 in a counterbalanced order.
|
Placebo/JZP-110
n=17 Participants
Placebo for 7 days or JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days) in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.0 years
STANDARD_DEVIATION 11.85 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 15.08 • n=7 Participants
|
51.6 years
STANDARD_DEVIATION 12.30 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
30 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
17 participants
n=5 Participants
|
17 participants
n=7 Participants
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 hours post-dosePopulation: One subject participated in only Treatment Period 1 and did not receive placebo resulting in 33 subjects in placebo group.
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 |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax)
|
19.92 centimeter (cm)
Standard Error 0.630
|
18.83 centimeter (cm)
Standard Error 0.627
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=32 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.
|
JZP-110
n=32 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.
|
|---|---|---|
|
SDLP at 6 Hours Post-dose
|
20.04 cm
Standard Error 0.632
|
19.24 cm
Standard Error 0.631
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
15 Participants
|
—
|
|
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-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
13 Participants
|
—
|
|
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-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
12 Participants
|
—
|
|
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-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
10 Participants
|
—
|
|
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-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
8 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Impaired
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Improved
|
5 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose
Impaired
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Improved
|
12 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
7 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
6 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Improved
|
9 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
6 Participants
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Improved
|
5 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Improved
|
4 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: 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 |
Placebo
n=34 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.
|
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.
|
|---|---|---|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Improved
|
3 Participants
|
—
|
|
Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose
Impaired
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in 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 |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
Standard Deviation of Speed (SDS) at 2 Hours Post-dose
|
2.55 kilometers/hour (km/hr)
Standard Error 0.099
|
2.62 kilometers/hour (km/hr)
Standard Error 0.098
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in 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 |
Placebo
n=32 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.
|
JZP-110
n=32 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.
|
|---|---|---|
|
SDS at 6 Hours Post-dose
|
2.84 km/hr
Standard Error 0.100
|
2.73 km/hr
Standard Error 0.099
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
Number of Lapses in Driving Test at 2 Hours Post-dose
|
2.89 number of lapses
Standard Error 0.566
|
1.76 number of lapses
Standard Error 0.558
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
Driving lapses (also known as lane drift, defined as deviations \> 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.
Outcome measures
| Measure |
Placebo
n=32 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.
|
JZP-110
n=32 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.
|
|---|---|---|
|
Number of Lapses in Driving Test at 6 Hours Post-dose
|
2.07 number of lapses
Standard Error 0.573
|
2.12 number of lapses
Standard Error 0.573
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec).
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose
|
6.37 lapses
Standard Error 2.111
|
2.71 lapses
Standard Error 2.077
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT \> 500 msec).
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=33 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.
|
|---|---|---|
|
PVT Number of Lapses at 6 Hours Post-dose
|
7.73 lapses
Standard Error 2.111
|
3.60 lapses
Standard Error 2.086
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured in msec.
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
PVT Mean Reaction Time at 2 Hours Post-dose
|
318.66 msec
Standard Error 19.307
|
286.55 msec
Standard Error 19.004
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured In msec.
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=33 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.
|
|---|---|---|
|
PVT Mean Reaction Time at 6 Hours Post-dose
|
341.37 msec
Standard Error 19.307
|
286.88 msec
Standard Error 19.188
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
PVT Inverse Reaction Time at 2 Hours Post-dose
|
3.59 (1/RT(ms))
Standard Error 0.111
|
3.69 (1/RT(ms))
Standard Error 0.110
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=33 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.
|
|---|---|---|
|
PVT Inverse Reaction Time at 6 Hours Post-dose
|
3.59 (1/RT(ms))
Standard Error 0.111
|
3.75 (1/RT(ms))
Standard Error 0.110
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec).
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
PVT Number of Errors of Commission at 2 Hours Post-dose
|
2.40 lapses
Standard Error 0.741
|
1.82 lapses
Standard Error 0.730
|
SECONDARY outcome
Timeframe: 6 hours post-dosePopulation: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT \< 100 msec).
Outcome measures
| Measure |
Placebo
n=33 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.
|
JZP-110
n=33 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.
|
|---|---|---|
|
PVT Number of Errors of Commission at 6 Hours Post-dose
|
2.46 lapses
Standard Error 0.741
|
1.76 lapses
Standard Error 0.740
|
SECONDARY outcome
Timeframe: Post Treatment at day 21Population: Subjects in the mITT population who did not have an assessment for a particular endpoint were excluded in the analysis of that endpoint.
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 |
Placebo
n=33 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.
|
JZP-110
n=34 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.
|
|---|---|---|
|
Toronto Hospital Alert Test (THAT)
|
23.94 score on a scale
Standard Error 1.180
|
27.52 score on a scale
Standard Error 1.162
|
Adverse Events
Placebo
JZP-110
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=33 participants at risk
Subjects received a single oral daily dose of placebo for 7 days in treatment period 1 or treatment period 2 in a counterbalanced order.
|
JZP-110
n=34 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) in treatment period 1 or treatment period 2 in a counterbalanced order.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
11.8%
4/34 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
|
Nervous system disorders
Dizziness
|
6.1%
2/33 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
8.8%
3/34 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
|
Nervous system disorders
Headache
|
12.1%
4/33 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
11.8%
4/34 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/33 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
11.8%
4/34 • 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. If a subject experienced more than 1 of a given adverse event (AE), the subject is counted only once for that AE.
|
Additional Information
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