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

JZP-110 is a phenylalanine derivative that is currently being investigated as a
potential treatment for excessive
sleepiness in narcolepsy and obstructive sleep apnea (OSA).

Patients with OSA are known to have impaired driving performance due to
drowsiness. This study is designed to assess effects of JZP-110 on driving
performance in patients with OSA. In addition, it is also of interest to assess
the effects of JZP-110 on measures of attention, response time, and risk-taking
or impulsivity. In this study, the psychomotor vigilance test (PVT) will be
used to assess psychomotor performance, with errors of commission on the PVT as
a measure of impulsivity.

Primary objective:
- To evaluate the effect of JZP-110 on driving performance

Secondary objectives:
- To evaluate the safety and tolerability of JZP-110
- To explore SAFTE (Sleep, Activity, Fatigue, and Task Effectiveness) modeling
using driving, Psychomotor Vigilance
Test (PVT) and sleep data

This trial is a randomized, double-blind, placebo-controlled, crossover study.

Subjects will be recruited at sleep clinics or Clinical Sites. Eligibility will
be determined through screening procedures including a Maintenance of
Wakefulness Test (MWT) after the washout of prohibited medications at Clinical
Sites and a practice driving test at the Driving Test Site. Eligible subjects
will be randomized to receive either JZP-110 (150 mg/day for 3 days, followed
by 300 mg/day for 4 days) or the matching placebo for 7 days, and will then
crossover to receive the other treatment for 7 days. On Day 7 of each treatment
period, all randomized subjects will have a study visit to undergo two driving
performance tests, one at 2 hours (between 1 to 3 hours) and the other at 6
hours (between 5 to 7 hours) after the morning dose.

The Psychomotor Vigilance Test (PVT) will be administered at pre-dose and prior
to each driving test. Actigraphy and a sleep diary will be used to assess daily
sleep patterns. The Toronto Hospital Alertness Test (THAT) will be administered
at baseline and the end of each treatment period. A follow-up visit will be
performed approximately 7 days after the final dose of study drug. The initial
two screening visits, including MWT assessment, and the follow-up visit will be
conducted at the Clinical Sites and the remaining Baseline visit and two
driving assessment visits will be conducted at the Driving Test Site. Safety
will be assessed throughout the study. Screening procedures will include
physical examination, electrocardiogram (ECG), and clinical laboratory tests. A
physical examination will be performed at completion of the study or at early
termination and adverse events will be collected and assessed throughout the
study. The Columbia- Suicide Severity Rating Scale (C-SSRS) will be completed
at screening and each visit.

7 days of JZP-110 (150 mg/day for 3 days, followed by 300 mg/day for 4 days)
and 7 days of placebo in counterbalanced order

- As in any study with a new drug known or (still) unknown side effects can
manifest themselves
- Very low risk of an accident while conducting the driving test (instructor
sits beside the patient during driving test)
- Depending on the drug that the patient is already using for the treatment of
narcolepsy it may be necessary that one stops the use of these, before one can
start with the intake of the study medication. Phasing out of the existing
medications could theoretically lead to risk. However, only a small proportion
of patients will have to reduce medication and patients in which in advance it
is estimated that this will pose a risk, will not be approached for the study.
- During their participation in the study, participants must wear an actigraph.
- Participants have to complete a sleep diary during their complete
participation in the study. Furthermore they have to keep track of when they
use their usual OSA treatment (sleep mask or dental prosthesis).
- During participation in the study subjects can possibly not drive a car by
themselves (i.e. from the time that the own medication, if any, will be phased
out until the last intake of study medication. Whether or not a subject is able
to continue driving during participation is determined by his/her physician and
discussed with him/her.