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Completed

NCT Number: NCT02919579

A Study to Evaluate the Effects of a Single-Dose and Repeat-Administration of Intranasal Esketamine on On-Road Driving in Participants With Major Depressive Disorder

The primary purpose of this study is to evaluate the effect of a single 84-milligram (mg) dose of intranasal esketamine compared to placebo, on next day driving performance and repeated administration of 84 mg intranasal esketamine on same-day driving performance as assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

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Key information

Conditions

Depressive Disorder, Major Depressive Disorder Mental Disorders Mood Disorders

Age range

22 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Leiden, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • If a woman, must have a negative serum beta human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test on Day 1 of Period 1 in Part A and prior to study drug administration in Part B
  • Comfortable with self-administration of intranasal medication and able to follow instructions provided
  • Normal visual acuity (corrected or uncorrected)
  • Based on self-report, able to consume an amount of alcohol that typically produces a blood alcohol concentration (BAC) of 0.05 percent (that is, 2 to 3 alcoholic drinks ingested within 2 hours on a single occasion)

Exclusion criteria

  • Current or prior diagnosis of psychosis/psychotic or bipolar disorder
  • Primary sleep disorder, such as insomnia, requiring pharmacological intervention at Screening
  • Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or Day 1 of Period 1 as deemed appropriate by the investigator
  • Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram (ECG) at screening or Day 1 of Period 1 as deemed appropriate by the investigator
  • History of moderate or severe use disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV or DSM-5) criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at screening and Day 1 of Period 1

Treatment and study plan

Placebo (Intranasal)

Drug

Participants will receive intranasal placebo in Part A (as per the treatment sequence in period 1,2 and 3) and Part B.

Esketamine

Drug

Participants will receive intranasal esketamine in Part A (as per the treatment sequence in period 1,2 and 3) and Part B.

Alcohol

Other

Participants will receive oral alcohol in Part A (as per the treatment sequence in period 1,2 and 3).

Placebo (Oral)

Drug

Participants will receive oral placebo in Part A (as per the treatment sequence in period 1,2 and 3).

Primary outcomes

  1. The Effect of a Single 84-Milligram (mg) Dose of Intranasal Esketamine Compared to Placebo, on Next day Driving Performance and Repeated Administration of 84 mg Intranasal Esketamine on Same-day Driving Performance

    Time frame: Part A: Day 2

    Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

  2. The Effect of a Single 84-mg Dose of Intranasal Esketamine Compared to Placebo, on Next day Driving Performance and Repeated Administration of 84 mg Intranasal Esketamine on Same-day Driving Performance

    Time frame: Part B: Day 1

    Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

  3. The Effect of a Single 84-mg Dose of Intranasal Esketamine Compared to Placebo, on Next day Driving Performance and Repeated Administration of 84 mg Intranasal Esketamine on Same-day Driving Performance

    Time frame: Part B: Day 11

    Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

  4. The Effect of a Single 84-mg Dose of Intranasal Esketamine Compared to Placebo, on Next day Driving Performance and Repeated Administration of 84 mg Intranasal Esketamine on Same-day Driving Performance

    Time frame: Part B: Day 18

    Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

  5. The Effect of a Single 84-mg Dose of Intranasal Esketamine Compared to Placebo, on Next day Driving Performance and Repeated Administration of 84 mg Intranasal Esketamine on Same-day Driving Performance

    Time frame: Part B: Day 25

    Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.

Secondary outcomes

  1. Effect on Subjective Driving Ability Scale

    Time frame: Part A: Day 2; Part B: Day 1, 11, 18 and 25

    Immediately after each driving test, subjects will indicate the perceived quality of their driving performance on a visual analog scale from 0 ('I drove exceptionally poorly') to 20 ('I drove exceptionally well') around a midpoint of 'I drove normally'.

  2. Karolinska Sleepiness Scale (KSS) Score

    Time frame: Part A: Day 2; Part B: Day 1, 11, 18 and 25

    KSS is a participant reported assessment used to rate sleepiness on a scale of 1 to 9, ranging from 'extremely alert' (1) to 'very sleepy, great effort to keep awake, fighting sleep (9).

  3. Efficacy Measured by the Montgomery Asberg Depression Rating Scale (MADRS)

    Time frame: Baseline; Part A: Predose, Day 2; Part B: Predose, Days 1, 11, 18, and 25; End of study (up to Day 98)

    MADRS consists of 10 items covering all the important complaints which Participant with depression have (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Item is scored from 0 (normal) to 6 (severe). Total score (0 to 60) is calculated by adding the scores of all 10 items. A higher score represents a more severe condition. Negative Change in Score Indicates Improvement.

  4. Effects on Suicidal Ideation/Behavior Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

    Time frame: Baseline; Part A: Predose, Day 2; Part B: Predose, Days 1, 11, 18, and 25; End of study (up to Day 98)

    C-SSRS is a clinician rated assessment of suicidal behavior and / or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.

  5. Effects on Dissociative Symptoms Using the Clinician-Administered Dissociative State Scale (CADSS)

    Time frame: Baseline; Part A: Predose, Day 1; Part B: Predose, Days 1, 11, 18, and 25

    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").

  6. Potential Relationship Between Changes in SDLP and the Plasma Concentration of Esketamine and Noresketamine

    Time frame: Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)

    Potential relationship will be assessed using visual displays of data. The relationship between the standard deviation of lateral position (SDLP) and the concentration of esketamine and noresketamine in plasma will be evaluated.

  7. Effect on Subjective Mental Effort Scale

    Time frame: Part A: Day 2; Part B: Day 1, 11, 18 and 25

    The level of mental effort the participant had to invest in performing the driving test will be assessed on a 15 centimeter (cm) visual analogue scale with markings ranging from 'absolutely no effort' to over 'extreme effort.

  8. Potential Relationship Between Changes in Mean Lateral Position (MLP) and the Plasma Concentration of Esketamine and Noresketamine

    Time frame: Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)

    Potential relationship will be assessed using visual displays of data. The relationship between the MLP and the concentration of esketamine and noresketamine in plasma will be evaluated. The MLP will be measured from a validated on-road driving test in a 100 kilometer (km) highway-driving lane.

  9. Potential Relationship Between Changes in Mean Speed and the Plasma Concentration of Esketamine and Noresketamine

    Time frame: Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)

    Potential relationship will be assessed using visual displays of data. The relationship between the mean speed (MS) and the concentration of esketamine and noresketamine in plasma will be evaluated. The MS will be measured from a validated on-road driving test in a 100 km highway-driving lane.

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

A Placebo- and Active-Controlled Study to Evaluate the Effects of a Single-Dose and Repeat-Administration of Intranasal Esketamine on On-Road Driving in Subjects With Major Depressive Disorder (DriveSaFe2)

Acronym: DriveSaFe2

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Sep 29, 2016
Registry last updated
Apr 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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