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

NCT02919579 | Completed Phase 1

• 3 other identifiers: CR1082282016-002424-8654135419TRD1019
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (5)

• 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

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

  Part A: Day 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

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

  Part B: Day 1

• 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

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

  Part B: Day 11

• 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

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

  Part B: Day 18

• 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

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

  Part B: Day 25

Secondary Outcomes (9)

• Effect on Subjective Driving Ability Scale

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

• Karolinska Sleepiness Scale (KSS) Score

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

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

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

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

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

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

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

Study Arms (7)

Part A: Sequence ABC (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive intranasal placebo on Day 1 and oral placebo on Day 2 \[Treatment A\] in Period 1, then intranasal placebo on Day 1 and Oral alcohol on Day 2 \[Treatment B\] in Period 2, followed by intranasal esketamine on Day 1 and oral placebo on Day 2 \[Treatment C\] in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part A: Sequence BCA (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive Treatment B in Period 1, then Treatment C in Period 2, followed by Treatment A in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part A: Sequence CAB (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive Treatment C in Period 1, then Treatment A in Period 2, followed by Treatment B in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part A: Sequence CBA (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive Treatment C in Period 1, then Treatment B in Period 2, followed by Treatment A in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part A: Sequence ACB (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive Treatment A in Period 1, then Treatment C in Period 2, followed by Treatment B in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part A: Sequence BAC (Placebo+Alcohol+Esketamine)

EXPERIMENTAL

Participants will receive Treatment B in Period 1, then Treatment A in Period 2, followed by Treatment C in Period 3.

Drug: Placebo (Intranasal); Drug: Esketamine; Other: Alcohol; Drug: Placebo (Oral)

Part B: Placebo+Esketamine

EXPERIMENTAL

Participants will receive intranasal placebo on Day 1, followed by intranasal esketamine on Days 4, 8, 11, 15, 18, 22 and 25.

Drug: Placebo (Intranasal); Drug: Esketamine

Interventions

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.

Part A: Sequence ABC (Placebo+Alcohol+Esketamine); Part A: Sequence ACB (Placebo+Alcohol+Esketamine); Part A: Sequence BAC (Placebo+Alcohol+Esketamine); Part A: Sequence BCA (Placebo+Alcohol+Esketamine); Part A: Sequence CAB (Placebo+Alcohol+Esketamine); Part A: Sequence CBA (Placebo+Alcohol+Esketamine); Part B: Placebo+Esketamine

Esketamine DRUG

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

Part A: Sequence ABC (Placebo+Alcohol+Esketamine); Part A: Sequence ACB (Placebo+Alcohol+Esketamine); Part A: Sequence BAC (Placebo+Alcohol+Esketamine); Part A: Sequence BCA (Placebo+Alcohol+Esketamine); Part A: Sequence CAB (Placebo+Alcohol+Esketamine); Part A: Sequence CBA (Placebo+Alcohol+Esketamine); Part B: Placebo+Esketamine

Alcohol OTHER

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

Part A: Sequence ABC (Placebo+Alcohol+Esketamine); Part A: Sequence ACB (Placebo+Alcohol+Esketamine); Part A: Sequence BAC (Placebo+Alcohol+Esketamine); Part A: Sequence BCA (Placebo+Alcohol+Esketamine); Part A: Sequence CAB (Placebo+Alcohol+Esketamine); Part A: Sequence CBA (Placebo+Alcohol+Esketamine)

Placebo (Oral) DRUG

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

Part A: Sequence ABC (Placebo+Alcohol+Esketamine); Part A: Sequence ACB (Placebo+Alcohol+Esketamine); Part A: Sequence BAC (Placebo+Alcohol+Esketamine); Part A: Sequence BCA (Placebo+Alcohol+Esketamine); Part A: Sequence CAB (Placebo+Alcohol+Esketamine); Part A: Sequence CBA (Placebo+Alcohol+Esketamine)

Eligibility Criteria

• Age: 22 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Leiden, Netherlands

Location

Related Publications (1)

• Dijkstra FM, van de Loo AJ, Abdulahad S, Bosma ER, Hartog M, Huls H, Kuijper DC, de Vries E, Solanki B, Singh J, Aluisio L, Zannikos P, Stuurman FE, Jacobs GE, Verster JC. The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder. J Psychopharmacol. 2022 May;36(5):614-625. doi: 10.1177/02698811221078764. Epub 2022 Feb 25.

  PMID: 35212235 DERIVED

Related Links

• 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)

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Esketamine; Ethanol

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 29, 2016
• Study Start: October 7, 2016
• Primary Completion: June 29, 2018
• Study Completion: June 29, 2018
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

NL (1)