The purpose of this study is to evaluate the effect of esketamine compared to placebo on driving performance as assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test in healthy participants.
This is a Phase 1, randomized (study medication assigned to participants by chance), double-blind (neither Investigator nor participant knows which treatment the participant receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), single-center, single-dose and 3-way crossover (the same medications provided to all participants but in different sequence) study of esketamine in healthy participants. Participants will be randomly assigned to 1 of 6 treatment sequences. The study will consist of 3 parts: Screening Phase (between 21 days and 1 day prior to the first dose administration), a 3-way crossover double-blind, single dose treatment Phase (45 days) and follow-up Phase (7 to 10 days after last dose administration). The maximum study duration for each participant will not exceed 7 weeks. Participants will receive either Treatment A (esketamine 84 milligram (mg) intranasal and 1 placebo capsule), Treatment B (placebo intranasal and 1 mirtazapine 30 mg capsule) or Treatment C (placebo intranasal and placebo capsule) in each treatment period. Driving performance will be assessed primarily by the mean difference of SDLP from an on road driving test. Participants' safety will be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
26
Esketamine 84 milligram (mg) \[3\*1 of spray in each nostril\] will be administered intranasally on Day 1 in one of the treatment periods.
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.
Placebo \[3\*1 in each nostril\] will be administered intranasally on Day 1 in one of the treatment periods.
Unnamed facility
Leiden, Netherlands
Standard Deviation of Lateral Position (SDLP) Assessed From an On-road Driving Test
The SDLP will be measured from a validated on-road driving test in a 100 kilometer (km) highway-driving lane.
Time frame: 4 to 14 hours post-dose
Standard Deviation of Speed (SDS) Assessed From an On-road Driving Test
The SDS will be measured from a validated on-road driving test in a 100 km highway-driving lane.
Time frame: 4 to 14 hours post-dose
Mean Speed (MS) Assessed From an On-road Driving Test
The MS will be measured from a validated on-road driving test in a 100 km highway-driving lane.
Time frame: 4 to 14 hours post-dose
Mean Lateral Position (MLP) Assessed From an On-road Driving Test
The MLP will be measured from a validated on-road driving test in a 100 km highway-driving lane.
Time frame: 4 to 14 hours post-dose
Subjective Driving Performance Score
Participants will indicate the perceived quality of their driving performance on a visual analog scale, which ranges from 0 ('I drove exceptionally poorly') to 20 ('I drove exceptionally well').
Time frame: After completion of driving test (4 to 14 hours post-dose)
Karolinska Sleepiness Scale (KSS) Score
The KSS is a participant-reported assessment used to rate sleepiness on a scale of 1 to 9, ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep).
Time frame: Pre-dose, 1, 2 hours and after completion of driving test (4 to 14 hours post-dose)
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Placebo capsule will be administered orally on Day 1 in one of the treatment periods.
Columbia Suicide Severity Rating Scale (C-SSRS) Score
The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior developed to assess severity and track suicidal events providing a summary of both suicidal ideation and behavior to identify the level and type of suicidality present.
Time frame: Up to 7 to 10 days after last dose administration
Brief Psychiatric Rating Scale (BPRS) Symptom Sub-Scale Score
The BPRS is an 18-item rating scale which is used to assess a range of psychotic and affective symptoms rated from both observation of the participant and the participant's own report. Only the 4-item positive symptom subscale (consisting of: suspiciousness/persecution, hallucinations, unusual thought content, and conceptual disorganization) will be used and each question is rated on a 7-point scale ranging from 0 (not present) to 6 (extremely severe).
Time frame: Pre-dose, 1 and 2 hours post-dose
Clinician Administered Dissociative States Scale (CADSS) Score
The CADSS is an instrument for the measurement of present-state dissociative symptoms. The CADSS comprises 23 subjective items, divided into 3 components: Depersonalization, Derealization and Amnesia. Participant's responses are coded on a 5-point scale (0 = "Not at all" through to 4 = "Extremely").
Time frame: Pre-dose, 1 and 2 hours post-dose
Maximum plasma concentration (Cmax)
The Cmax is the maximum observed plasma concentration of esketamine or noresketamine.
Time frame: Pre-dose, 0.5, 1, 3 and 4 hours post-dose