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

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 narcolepsy 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 narcolepsy. 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 careful confirmation of
narcolepsy diagnosis at the Clinical Sites and after 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. Subjects who are taking excluded medications must washout
all the excluded medications per the prescribed schedule, including any
stimulants or alerting agents, sodium oxybate, and sedatives/hypnotics, prior
to the first dose of the study drug. 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 the end of each treatment period. A follow-up visit
will be performed approximately 7 days after the final treatment. The initial
screening visit, 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 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 the 14 days when the study
drug is taken.
- During the medication period of 14 days, participants must not drive a car by
themselves.