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

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ClinicalTrials.gov Identifier: NCT02228239
Recruitment Status : Completed
First Posted : August 28, 2014
Last Update Posted : December 30, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Esketamine Drug: Mirtazapine Drug: Placebo (Matched to Esketamine) Drug: Placebo (Matched to Mirtazapine) Phase 1

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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
Study Start Date : September 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Mirtazapine

Arm Intervention/treatment
Experimental: Sequence 1 (ABC)
Participants will receive Treatment A (esketamine 84 milligram (mg) intranasally and 1 placebo capsule) in Period 1, Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 2 and Treatment C (placebo intranasally and placebo capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Experimental: Sequence 2 (BCA)
Participants will receive Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 1, Treatment C (placebo intranasally and placebo capsule) in Period 2 and Treatment A (esketamine 84 mg intranasally and 1 placebo capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Experimental: Sequence 3 (CAB)
Participants will receive Treatment C (placebo intranasally and placebo capsule) in Period 1, Treatment A (esketamine 84 mg intranasally and 1 placebo capsule) in Period 2 and Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Experimental: Sequence 4 (CBA)
Participants will receive Treatment C (placebo intranasally and placebo capsule) in Period 1, Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 2 and Treatment A (esketamine 84 mg intranasally and 1 placebo capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Experimental: Sequence 5 (ACB)
Participants will receive Treatment A (esketamine 84 mg intranasally and 1 placebo capsule) in Period 1, Treatment C (placebo intranasally and placebo capsule) in Period 2 and Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.

Experimental: Sequence 6 (BAC)
Participants will receive Treatment B (placebo intranasally and 1 mirtazapine 30 mg capsule) in Period 1, Treatment A (esketamine 84 mg intranasally and 1 placebo capsule) in Period 2 and Treatment C (placebo intranasally and placebo capsule) in Period 3 with a washout interval of at least 6 days between treatment periods.
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.
Other Name: JNJ-54135419

Drug: Mirtazapine
Mirtazapine 30 mg capsule will be administered orally on Day 1 in one of the treatment periods.

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

Drug: Placebo (Matched to Mirtazapine)
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.




Primary Outcome Measures :
  1. Standard Deviation of Lateral Position (SDLP) Assessed From an On-road Driving Test [ Time Frame: 4 to 14 hours post-dose ]
    The SDLP will be measured from a validated on-road driving test in a 100 kilometer (km) highway-driving lane.


Secondary Outcome Measures :
  1. Standard Deviation of Speed (SDS) Assessed From an On-road Driving Test [ Time Frame: 4 to 14 hours post-dose ]
    The SDS will be measured from a validated on-road driving test in a 100 km highway-driving lane.

  2. Mean Speed (MS) Assessed From an On-road Driving Test [ Time Frame: 4 to 14 hours post-dose ]
    The MS will be measured from a validated on-road driving test in a 100 km highway-driving lane.

  3. Mean Lateral Position (MLP) Assessed From an On-road Driving Test [ Time Frame: 4 to 14 hours post-dose ]
    The MLP will be measured from a validated on-road driving test in a 100 km highway-driving lane.

  4. Subjective Driving Performance Score [ Time Frame: After completion of driving test (4 to 14 hours post-dose) ]
    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').

  5. Karolinska Sleepiness Scale (KSS) Score [ Time Frame: Pre-dose, 1, 2 hours and after completion of driving test (4 to 14 hours post-dose) ]
    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).

  6. Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Up to 7 to 10 days after last dose administration ]
    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.

  7. Brief Psychiatric Rating Scale (BPRS) Symptom Sub-Scale Score [ Time Frame: Pre-dose, 1 and 2 hours post-dose ]
    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).

  8. Clinician Administered Dissociative States Scale (CADSS) Score [ Time Frame: Pre-dose, 1 and 2 hours post-dose ]
    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").

  9. Maximum plasma concentration (Cmax) [ Time Frame: Pre-dose, 0.5, 1, 3 and 4 hours post-dose ]
    The Cmax is the maximum observed plasma concentration of esketamine or noresketamine.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

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): NCT02228239


Locations
Netherlands
Leiden, Netherlands
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02228239     History of Changes
Other Study ID Numbers: CR104764
2014-002005-38 ( EudraCT Number )
ESKETINTRD1006 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 28, 2014    Key Record Dates
Last Update Posted: December 30, 2014
Last Verified: December 2014

Keywords provided by Janssen Research & Development, LLC:
Healthy
Esketamine
Mirtazapine
Psychomotor.

Additional relevant MeSH terms:
Mirtazapine
Mianserin
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Serotonin Antagonists
Serotonin Agents
Antidepressive Agents, Second-Generation