Study to Assess the Effects of Esketamine on Safety of On-road Driving in Healthy Participants

Healthy Clinical Trial

— DRiVESaFe  

Official title:

A Double-blind, Randomized, Placebo-Controlled, 3-way Crossover Study to Evaluate the Single Dose Effects of Intranasal Esketamine on Safety of On-Road Driving in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02228239
• Other study ID #: CR104764
• Secondary ID: 2014-002005-38ES
• Status: Completed
• Phase: Phase 1
• First received: August 27, 2014
• Last updated: December 29, 2014
• Start date: September 2014
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 60 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) (weight [kg]/height^2[m^2]) between 18 and 30 kg/m^2 (inclusive), and body weight not less than 45 kg

• Blood pressure (after the participants is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic at Screening and pre-dose on Day 1 of Period 1

• A woman of childbearing potential must have a negative urine pregnancy test at Screening and pre-dose on Day 1 of Period 1

• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at Screening and pre-dose on Day 1 of Period 1, including: sinus rhythm, heart rate between 45 and 90 beats per minute (bpm), QTc interval less than or equal to 450 milliseconds (ms), QRS interval of less than 120 ms, PR interval less than 200 ms and morphology consistent with healthy cardiac conduction and function 1st degree AV block is exclusionary

• Participant has a valid driving license for more than 3 years, has driven at least 5000 kilometer (km) in the past year and is driving a car regularly

Exclusion Criteria:

• Participant has clinically significant liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic (including cataplexy and cognitive impairment), hematologic, rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary

• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at Screening, as deemed appropriate by the Investigator

• Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram (ECG) at Screening or on Day 1 of Period 1, as deemed appropriate by the Investigator

• Anatomical or medical conditions that may impede delivery or absorption of study medication (for example, undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; or signs and symptoms of rhinitis predose on Day 1 of Period 1)

• Has an abnormal or deviated nasal septum with any one or more of the following symptoms: blockage of one or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Esketamine
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
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.
• Placebo (Matched to Esketamine)
Placebo [3*1 in each nostril] will be administered intranasally on Day 1 in one of the treatment periods.
• Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 to 14 hours post-dose	No
Secondary	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.	4 to 14 hours post-dose	No
Secondary	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.	4 to 14 hours post-dose	No
Secondary	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.	4 to 14 hours post-dose	No
Secondary	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').	After completion of driving test (4 to 14 hours post-dose)	No
Secondary	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).	Pre-dose, 1, 2 hours and after completion of driving test (4 to 14 hours post-dose)	No
Secondary	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.	Up to 7 to 10 days after last dose administration	Yes
Secondary	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).	Pre-dose, 1 and 2 hours post-dose	Yes
Secondary	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").	Pre-dose, 1 and 2 hours post-dose	Yes
Secondary	Maximum plasma concentration (Cmax)	The Cmax is the maximum observed plasma concentration of esketamine or noresketamine.	Pre-dose, 0.5, 1, 3 and 4 hours post-dose	No