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

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ClinicalTrials.gov Identifier: NCT02806895
Recruitment Status : Completed
First Posted : June 21, 2016
Results First Posted : June 16, 2020
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Brief Summary:
This trial is a randomized, double-blind, placebo-controlled, crossover study to evaluate the effect of JZP-110 on driving performance in subjects with excessive sleepiness due to obstructive sleep apnea.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Excessive Sleepiness Drug: JZP-110 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Obstructive Sleep Apnea
Actual Study Start Date : July 5, 2016
Actual Primary Completion Date : May 28, 2019
Actual Study Completion Date : May 28, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

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




Primary Outcome Measures :
  1. Standard Deviation of Lateral Position (SDLP) at 2 Hours Post-dose (Approximately at Tmax) [ Time Frame: 2 hours post-dose ]
    Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.


Secondary Outcome Measures :
  1. SDLP at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Subjects were instructed to drive with steady lateral position between the delineated boundaries of the slower (right) traffic lane, while maintaining a constant speed of 95 kilometers (km) per hour (hr). Deviation was measured by the vehicle's speed and lateral distance to the left lane line and was continuously recorded. Individual improvement was defined as a decrease in SDLP below the negative value of threshold; individual impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  2. Number of Subjects With Improved or Impaired Driving at a Threshold 1 Centimeter (cm) on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  3. Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  4. Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  5. Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  6. Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  7. Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 2 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 2 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  8. Number of Subjects With Improved or Impaired Driving at a Threshold 1.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  9. Number of Subjects With Improved or Impaired Driving at a Threshold 1.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  10. Number of Subjects With Improved or Impaired Driving at a Threshold 2.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  11. Number of Subjects With Improved or Impaired Driving at a Threshold 2.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  12. Number of Subjects With Improved or Impaired Driving at a Threshold 3.0 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  13. Number of Subjects With Improved or Impaired Driving at a Threshold 3.5 cm on JZP-110 Compared to Placebo 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Individual changes (solriamfetol minus placebo) in driving performance were measured by SDLP at 6 hours postdose. The Maximum McNemar symmetry analyses was used to detect an asymmetry in the distribution of the change in driving performance at 6 hours postdose. The test examined the differences in the proportions of impaired drivers and improved drivers following treatment using a generalized single McNemar test statistics were obtained at each threshold (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 cm), which was the vehicle weaving amount. Changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant. Improvement was defined as a decrease in SDLP comparing JZP-110 and placebo below the threshold and impairment was defined as an increase in SDLP above the threshold or failure to complete the driving test due to sleepiness or subjects related safety concerns.

  14. Standard Deviation of Speed (SDS) at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed.

  15. SDS at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Mean SDS was a common measure of the driver's ability to maintain a constant driving speed. Variations in driving speed were recorded and analyzed.

  16. Number of Lapses in Driving Test at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    Driving lapses (also known as lane drift, defined as deviations > 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.

  17. Number of Lapses in Driving Test at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    Driving lapses (also known as lane drift, defined as deviations > 100 cm from the mean lateral position and from the absolute lateral position for 8 seconds. Driving performance will be assessed using a standardized on-road driving test on Day 7 (Visit 4) and on Day 14 (Visit 5). A practice driving test will be done during the screening period to familiarize the subject with the vehicle and test scenario, assess if the subject can adequately operate the manual transmission vehicle, and determine if any safety concerns exist that exclude the subject from participating in the study.

  18. Psychomotor Vigilance Test (PVT) Number of Lapses at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT > 500 msec).

  19. PVT Number of Lapses at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Lapses were measured as (RT > 500 msec).

  20. PVT Mean Reaction Time at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured in msec.

  21. PVT Mean Reaction Time at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Mean RT is measured In msec.

  22. PVT Inverse Reaction Time at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.

  23. PVT Inverse Reaction Time at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Inverse reaction time was expressed as 1/reaction time in msec.

  24. PVT Number of Errors of Commission at 2 Hours Post-dose [ Time Frame: 2 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT < 100 msec).

  25. PVT Number of Errors of Commission at 6 Hours Post-dose [ Time Frame: 6 hours post-dose ]
    The PVT was administered at screening for practice only, and at pre-dose and within 30 minutes before each driving test on Days 7 and 14 (Visits 4 and 5, respectively). The test was administered over 10 minutes with visual stimuli appearing randomly at variable intervals of 2 to 10 seconds. Subjects were instructed to respond to the appearance of a visual stimulus on a computer screen by pushing a response button as quickly as possible. Errors of commission were measured as the number of responses without a stimulus or false starts with (RT < 100 msec).

  26. Toronto Hospital Alert Test (THAT) [ Time Frame: Post Treatment at day 21 ]
    THAT is a 10-item self-report questionnaire designed to measure perceived alertness in the preceding week. The THAT was administered at baseline and the end of each treatment period. The total score of THAT can range between 0 to 50 where the higher score indicates greater alertness.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age 21 to 65 years inclusive
  2. Diagnosis of obstructive sleep apnea (OSA) per International Classification of Sleep Disorders (ICSD-3)
  3. BMI 18 to <40 kg/m2
  4. Willing and able to provide written informed consent

Exclusion Criteria:

  1. Female subjects who are pregnant, nursing, or lactating
  2. Any other clinically relevant medical, behavioral, or psychiatric disorder other than OSA that is associated with excessive sleepiness
  3. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria
  4. History or presence of any unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy and/or safety assessments per the judgment of the investigator
  5. History of bariatric surgery within the past year or a history of any gastric bypass procedure
  6. Presence or history of significant cardiovascular disease
  7. Unable to washout or refrain from taking any over-the-counter (OTC) or prescription medications that could affect sleep-wake function

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02806895


Locations
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Netherlands
Maastricht University
Maastricht, Limburg, Netherlands, 6229
Sponsors and Collaborators
Jazz Pharmaceuticals
Investigators
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Study Director: Grace Wang, MD Jazz Pharmaceuticals
Principal Investigator: Jan Ramaekers, PhD Maastricht University
  Study Documents (Full-Text)

Documents provided by Jazz Pharmaceuticals:
Study Protocol  [PDF] April 28, 2016
Statistical Analysis Plan  [PDF] August 9, 2019

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Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02806895    
Other Study ID Numbers: 15-004
2015-003930-28 ( EudraCT Number )
First Posted: June 21, 2016    Key Record Dates
Results First Posted: June 16, 2020
Last Update Posted: January 14, 2021
Last Verified: December 2020
Keywords provided by Jazz Pharmaceuticals:
Driving
Additional relevant MeSH terms:
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Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Disorders of Excessive Somnolence
Sleepiness
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders