Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects with Excessive Sleepiness Due to Narcolepsy
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Summary
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EudraCT number |
2015-003931-36 |
Trial protocol |
NL DE |
Global end of trial date |
19 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Jun 2020
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First version publication date |
17 Jun 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
15-005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02806908 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Jazz Pharmaceuticals Inc.
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Sponsor organisation address |
3170 Porter Drive, Palo Alto, United States, 94304
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Public contact |
Director, Disclosure & Transparency, Director, Disclosure & Transparency, 001 2158323750, ClinicalTrialDisclosure@JazzPharma.com
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Scientific contact |
Grace Wang, MD, Director, Disclosure & Transparency, 001 2158323750, ClinicalTrialDisclosure@JazzPharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 May 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 May 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
1. To evaluate the effect of JZP-110 on driving performance
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Protection of trial subjects |
All subjects were to provide written informed consent, in accordance with local IEC/IRB requirements, before the performance of any study-related procedures.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Feb 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
24
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
24
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The screening phase involved a standard medical screening visit. Following screening, subjects entered the crossover treatment phase. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Data analyst, Carer, Assessor, Subject | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Subjects received a single oral daily dose of placebo for 7 days in treatment period 1 or treatment period 2 in a counterbalanced order. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single oral daily dose of placebo for 7 days in Treatment Period 1 or Treatment Period 2 in a counterbalanced order.
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Arm title
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JZP-110 | ||||||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
solriamfetol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
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.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: This was a crossover study where all subjects received placebo and JZP-110 in a counterbalanced order between treatment sequence 1 and treatment sequence 2. System error as system automatically doubles the enrollment. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: This was a crossover study where all subjects received placebo and JZP-110 in a counterbalanced order between treatment sequence 1 and treatment sequence 2. System error as system automatically doubles the enrollment. [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: This was a crossover study where all subjects received placebo and JZP-110 in a counterbalanced order between treatment sequence 1 and treatment sequence 2. System error as system automatically doubles the enrollment. [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: This was a crossover study where all subjects received placebo and JZP-110 in a counterbalanced order between treatment sequence 1 and treatment sequence 2. System error as system automatically doubles the enrollment. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received a single oral daily dose of placebo for 7 days in treatment period 1 or treatment period 2 in a counterbalanced order. | ||
Reporting group title |
JZP-110
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Reporting group description |
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. | ||
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End point title |
Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax) | ||||||||||||
End point description |
Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
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End point type |
Primary
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End point timeframe |
2 hours post-dose
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| Notes [1] - The modified intent to treat (mITT) population consisted of 22 subjects. [2] - The modified intent to treat (mITT) population consisted of 22 subjects. |
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Statistical analysis title |
SDLP at 2 Hours Post-dose (Approximately at Tmax) | ||||||||||||
Statistical analysis description |
The normality assumption, was not satisfied, therefore the Wilcoxon signed-rank test was used to compare the pairwise treatment differences for SDLP at 6 hours postdose. Total subjects in this analysis set was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0022 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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End point title |
SDLP at 6 Hours Post-dose | ||||||||||||
End point description |
Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.
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End point type |
Secondary
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End point timeframe |
6 hours post-dose
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| Notes [3] - Subjects in the mITT population missing an assessment for an endpoint were excluded in the analysis. |
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Statistical analysis title |
SDLP at 6 Hours Post-dose | ||||||||||||
Statistical analysis description |
The normality assumption, was not satisfied, therefore the Wilcoxon signed-rank test was used to compare the pairwise treatment differences for SDLP at 6 hours postdose. Total subjects in this analysis set was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
43
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0416 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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End point title |
Proportion of Subjects With Improved or Impaired Driving on JZP-110 Compared to Placebo 2 Hours Post-dose | |||||||||
End point description |
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. The maximum
McNemar's statistic was used as the test statistic.
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End point type |
Secondary
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End point timeframe |
2 hours post-dose
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| Notes [4] - The distribution of the change in driving performance (JZP-110/Placebo) could not be concluded. [5] - The distribution of the change in driving performance (JZP-110/Placebo) could not be concluded. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Proportion of Subjects with Improved or Impaired Driving on JZP-110 Compared to Placebo 6 Hours Post-dose | |||||||||
End point description |
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. The maximum McNemar’s statistic was used as the test statistic.
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End point type |
Secondary
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End point timeframe |
6 hours post-dose
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| Notes [6] - The distribution of the change in driving performance (JZP-110/Placebo) could not be concluded. [7] - The distribution of the change in driving performance (JZP-110/Placebo) could not be concluded. |
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End point title |
Standard Deviation of Speed (SDS) at 2 Hours Post-dose | ||||||||||||
End point description |
Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and
analyzed.
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End point type |
Secondary
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End point timeframe |
2 hours post-dose
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Statistical analysis title |
SDS 2 Hours Post-dose | ||||||||||||
Statistical analysis description |
The Driving Performance parameter was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), driving performance test (2 hours post-dose), treatment period, treatment sequence and treatment by driving performance test interaction as fixed effects and subject as a random effect. Total subjects in this analysis set was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1141 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
SDS at 6 Hours Post-dose | ||||||||||||
End point description |
Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and
analyzed.
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End point type |
Secondary
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End point timeframe |
6 hours post-dose
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| Notes [8] - Subjects in the mITT population missing an assessment for an endpoint were excluded in the analysis. |
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Statistical analysis title |
SDS 6 Hours Post-dose | ||||||||||||
Statistical analysis description |
The Driving Performance parameter was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), driving performance test (6 hours post-dose), treatment period, treatment sequence and treatment by driving performance test interaction as fixed effects and subject as a random effect. Total subjects in this analysis set was 21 for Placebo and 22 for JZP-110 not a total of 43 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
43
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.4441 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Number of Lapses in Driving Test at 2 Hours Post-dose | ||||||||||||
End point description |
Number of driving lapses (also known as lane drift, was defined as deviations > 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test was done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject could adequately operate the manual transmission vehicle, and determine if any safety concerns existed that excluded the subject from participating in the study.
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End point type |
Secondary
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End point timeframe |
2 hours post-dose
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Statistical analysis title |
Total Number of Lapses in Driving Test at 2 Hours | ||||||||||||
Statistical analysis description |
The Driving Performance parameter was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), driving performance test (2 hours post-dose), treatment period, treatment sequence and treatment by driving performance test interaction as fixed effects and subject as a random effect. Total subjects in this analysis set was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.3423 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Number of Lapses in Driving Test at 6 Hours Post-dose | ||||||||||||
End point description |
Number of driving lapses (also known as lane drift, was defined as deviations > 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test was done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject could adequately operate the manual transmission vehicle, and determine if any safety concerns existed that excluded the subject from participating in the study.
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End point type |
Secondary
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End point timeframe |
6 hours post-dose
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| Notes [9] - Subjects in the mITT population missing an assessment for an endpoint were excluded in the analysis. |
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Statistical analysis title |
Total Number of Lapses in Driving Test at 6 Hours | ||||||||||||
Statistical analysis description |
The Driving Performance parameter was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), driving performance test (6 hours post-dose), treatment period, treatment sequence and treatment by driving performance test interaction as fixed effects and subject as a random effect. Total subjects in this analysis set was 21 for Placebo and 22 for JZP-110 not a total of 43 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
43
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9384 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Lapses were measured as (RT > 500 msec).
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End point type |
Secondary
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End point timeframe |
2 hours post-dose
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Statistical analysis title |
PVT Number of Lapses at 2 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (2 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Number of errors of commission: number of responses without a stimulus, or false starts Inverse reaction time. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0939 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
PVT Number of Lapses at 6 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Lapses were measured as (RT > 500 msec).
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End point type |
Secondary
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End point timeframe |
6 hours post-dose
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Statistical analysis title |
PVT Number of Lapses at 6 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (6 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Number of errors of commission: number of responses without a stimulus, or false starts Inverse reaction time. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0246 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
PVT Mean Reaction Time at 2 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Mean RT is measured in msec.
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End point type |
Secondary
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End point timeframe |
2 hours post-dose
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Statistical analysis title |
PVT Mean Reaction Time at 2 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (2 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Inverse reaction time: Each RT (ms) was divided by 1,000 and reciprocally transformed. The transformed values were then averaged. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
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Comparison groups |
Placebo v JZP-110
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1475 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
PVT Mean Reaction Time at 6 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Mean RT is measured In msec.
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End point type |
Secondary
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End point timeframe |
6 hours post dose
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Statistical analysis title |
PVT Mean Reaction Time at 6 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (6 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Inverse reaction time: Each RT (ms) was divided by 1,000 and reciprocally transformed. The transformed values were then averaged. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
|
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Comparison groups |
Placebo v JZP-110
|
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Number of subjects included in analysis |
44
|
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Analysis specification |
Pre-specified
|
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1513 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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|
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End point title |
PVT Inverse Reaction Time at 2 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
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End point type |
Secondary
|
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End point timeframe |
2 hours post-dose
|
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|
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Statistical analysis title |
PVT Inverse Reaction Time at 2 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (2 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Inverse reaction time: Each RT (ms) was divided by 1,000 and reciprocally transformed. The transformed values were then averaged. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
|
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Comparison groups |
Placebo v JZP-110
|
||||||||||||
Number of subjects included in analysis |
44
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0002 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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|
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End point title |
PVT Inverse Reaction Time at 6 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
6 hours post-dose
|
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|
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Statistical analysis title |
PVT Inverse Reaction Time at 6 Hours Post-dose | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (6 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Inverse reaction time: Each RT (ms) was divided by 1,000 and reciprocally transformed. The transformed values were then averaged. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
|
||||||||||||
Comparison groups |
Placebo v JZP-110
|
||||||||||||
Number of subjects included in analysis |
44
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0005 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
|||||||||||||
|
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End point title |
PVT Number of Errors of Commission at 2 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT < 100 msec).
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
2 hours post-dose
|
||||||||||||
|
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Statistical analysis title |
PVT Number of Errors of Commission at 2 Hours Post | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (2 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Number of errors of commission: number of responses without a stimulus, or false starts Inverse reaction time. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
|
||||||||||||
Comparison groups |
Placebo v JZP-110
|
||||||||||||
Number of subjects included in analysis |
44
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4774 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
|||||||||||||
|
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End point title |
PVT Number of Errors of Commission at 6 Hours Post-dose | ||||||||||||
End point description |
The PVT was administered at screening for practice only, and at predose and within 30 minutes before each driving test on Days 7 and 14
(Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10
seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as
quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT < 100 msec).
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
6 hours post-dose
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
PVT Number of Errors of Commission at 6 Hours Post | ||||||||||||
Statistical analysis description |
PVT was analyzed using a repeated mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), PVT test (6 hours post-dose), treatment period, treatment sequence and treatment by PVT test interaction as fixed effects and subject as a random effect. Number of errors of commission: number of responses without a stimulus, or false starts Inverse reaction time. Total subjects was 22 for Placebo and 22 for JZP-110 not a total of 44 due to cross over design.
|
||||||||||||
Comparison groups |
Placebo v JZP-110
|
||||||||||||
Number of subjects included in analysis |
44
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.3801 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
|||||||||||||
|
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End point title |
Toronto Hospital Alert Test (THAT) | ||||||||||||
End point description |
The Toronto Hospital Alert Test (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.
|
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End point type |
Secondary
|
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End point timeframe |
post treatment
|
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|
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Statistical analysis title |
THAT | ||||||||||||
Statistical analysis description |
THAT was analyzed using a mixed effect ANOVA model. The model included treatment (JZP-110 and placebo), treatment period, treatment sequence as fixed effects and subject as a random effect. Total subjects in this analysis set was 22 for Placebo and 22 JZP-110 not a total of 44 due to cross over design.
|
||||||||||||
Comparison groups |
Placebo v JZP-110
|
||||||||||||
Number of subjects included in analysis |
44
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
|||||||||||||
|
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Adverse events information
|
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Timeframe for reporting adverse events |
Adverse events were reported from the time written informed consent was obtained until the final study visit or early termination.
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Adverse event reporting additional description |
The Safety Population consisted of all subjects who received at least 1 dose of study medication. A treatment-emergent AE (TEAE), was defined as an AE that either began after first study drug dose or worsened after the first dose. When determining the percent of subjects who experienced an AE, multiple increases in severity were counted as one AE.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
|
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Reporting group title |
Placebo
|
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Reporting group description |
Subjects received a single oral daily dose of placebo for 7 days | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
JZP-110
|
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Reporting group description |
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) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
