- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02228239
Study to Assess the Effects of Esketamine on Safety of On-road Driving in Healthy Participants (DRiVESaFe)
December 29, 2014 updated by: Janssen Research & Development, LLC
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
26
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Leiden, Netherlands
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
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 Names:
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.
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.
|
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 Names:
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.
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.
|
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 Names:
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.
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.
|
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 Names:
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.
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.
|
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 Names:
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.
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.
|
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 Names:
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.
Placebo capsule will be administered orally on Day 1 in one of the treatment periods.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
4 to 14 hours post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
4 to 14 hours post-dose
|
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.
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4 to 14 hours post-dose
|
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 to 14 hours post-dose
|
Subjective Driving Performance Score
Time Frame: After completion of driving test (4 to 14 hours post-dose)
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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').
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After completion of driving test (4 to 14 hours post-dose)
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Karolinska Sleepiness Scale (KSS) Score
Time Frame: Pre-dose, 1, 2 hours and after completion of driving test (4 to 14 hours post-dose)
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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).
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Pre-dose, 1, 2 hours and after completion of driving test (4 to 14 hours post-dose)
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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.
|
Up to 7 to 10 days after last dose administration
|
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).
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Pre-dose, 1 and 2 hours post-dose
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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").
|
Pre-dose, 1 and 2 hours post-dose
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Maximum plasma concentration (Cmax)
Time Frame: Pre-dose, 0.5, 1, 3 and 4 hours post-dose
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The Cmax is the maximum observed plasma concentration of esketamine or noresketamine.
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Pre-dose, 0.5, 1, 3 and 4 hours post-dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2014
Primary Completion (Actual)
December 1, 2014
Study Completion (Actual)
December 1, 2014
Study Registration Dates
First Submitted
August 27, 2014
First Submitted That Met QC Criteria
August 27, 2014
First Posted (Estimate)
August 28, 2014
Study Record Updates
Last Update Posted (Estimate)
December 30, 2014
Last Update Submitted That Met QC Criteria
December 29, 2014
Last Verified
December 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Antidepressive Agents
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin Antagonists
- Anti-Anxiety Agents
- Serotonin 5-HT3 Receptor Antagonists
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Adrenergic alpha-Antagonists
- Adrenergic alpha-2 Receptor Antagonists
- Esketamine
- Mirtazapine
Other Study ID Numbers
- CR104764
- 2014-002005-38 (EudraCT Number)
- ESKETINTRD1006 (Other Identifier: Janssen Research & Development, LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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