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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 (DriveSaFe2)

Primary Purpose

Depressive Disorder, Major

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Placebo (Intranasal)
Esketamine
Alcohol
Placebo (Oral)
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depressive Disorder, Major

Eligibility Criteria

22 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

Part B: Placebo+Esketamine

Arm Description

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.

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.

Secondary Outcome Measures

Effect on Subjective Driving Ability Scale
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'.
Karolinska Sleepiness Scale (KSS) Score
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).
Efficacy Measured by the Montgomery Asberg Depression Rating Scale (MADRS)
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.
Effects on Suicidal Ideation/Behavior Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
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.
Effects on Dissociative Symptoms Using the Clinician-Administered Dissociative State Scale (CADSS)
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").
Potential Relationship Between Changes in SDLP and the Plasma Concentration of Esketamine and Noresketamine
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.
Effect on Subjective Mental Effort Scale
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.
Potential Relationship Between Changes in Mean Lateral Position (MLP) and the Plasma Concentration of Esketamine and Noresketamine
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.
Potential Relationship Between Changes in Mean Speed and the Plasma Concentration of Esketamine and Noresketamine
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.

Full Information

First Posted
September 1, 2016
Last Updated
April 23, 2019
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02919579
Brief Title
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
Acronym
DriveSaFe2
Official 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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
October 7, 2016 (Actual)
Primary Completion Date
June 29, 2018 (Actual)
Study Completion Date
June 29, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A: Sequence ABC (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A: Sequence BCA (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
Participants will receive Treatment B in Period 1, then Treatment C in Period 2, followed by Treatment A in Period 3.
Arm Title
Part A: Sequence CAB (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
Participants will receive Treatment C in Period 1, then Treatment A in Period 2, followed by Treatment B in Period 3.
Arm Title
Part A: Sequence CBA (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
Participants will receive Treatment C in Period 1, then Treatment B in Period 2, followed by Treatment A in Period 3.
Arm Title
Part A: Sequence ACB (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
Participants will receive Treatment A in Period 1, then Treatment C in Period 2, followed by Treatment B in Period 3.
Arm Title
Part A: Sequence BAC (Placebo+Alcohol+Esketamine)
Arm Type
Experimental
Arm Description
Participants will receive Treatment B in Period 1, then Treatment A in Period 2, followed by Treatment C in Period 3.
Arm Title
Part B: Placebo+Esketamine
Arm Type
Experimental
Arm Description
Participants will receive intranasal placebo on Day 1, followed by intranasal esketamine on Days 4, 8, 11, 15, 18, 22 and 25.
Intervention Type
Drug
Intervention Name(s)
Placebo (Intranasal)
Intervention Description
Participants will receive intranasal placebo in Part A (as per the treatment sequence in period 1,2 and 3) and Part B.
Intervention Type
Drug
Intervention Name(s)
Esketamine
Intervention Description
Participants will receive intranasal esketamine in Part A (as per the treatment sequence in period 1,2 and 3) and Part B.
Intervention Type
Other
Intervention Name(s)
Alcohol
Intervention Description
Participants will receive oral alcohol in Part A (as per the treatment sequence in period 1,2 and 3).
Intervention Type
Drug
Intervention Name(s)
Placebo (Oral)
Intervention Description
Participants will receive oral placebo in Part A (as per the treatment sequence in period 1,2 and 3).
Primary Outcome Measure Information:
Title
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
Description
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Time Frame
Part A: Day 2
Title
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
Description
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Time Frame
Part B: Day 1
Title
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
Description
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Time Frame
Part B: Day 11
Title
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
Description
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Time Frame
Part B: Day 18
Title
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
Description
Driving performance will be assessed by the mean difference of standard deviation of lateral position (SDLP) from an on-road driving test.
Time Frame
Part B: Day 25
Secondary Outcome Measure Information:
Title
Effect on Subjective Driving Ability Scale
Description
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'.
Time Frame
Part A: Day 2; Part B: Day 1, 11, 18 and 25
Title
Karolinska Sleepiness Scale (KSS) Score
Description
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).
Time Frame
Part A: Day 2; Part B: Day 1, 11, 18 and 25
Title
Efficacy Measured by the Montgomery Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
Baseline; Part A: Predose, Day 2; Part B: Predose, Days 1, 11, 18, and 25; End of study (up to Day 98)
Title
Effects on Suicidal Ideation/Behavior Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
Baseline; Part A: Predose, Day 2; Part B: Predose, Days 1, 11, 18, and 25; End of study (up to Day 98)
Title
Effects on Dissociative Symptoms Using the Clinician-Administered Dissociative State Scale (CADSS)
Description
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").
Time Frame
Baseline; Part A: Predose, Day 1; Part B: Predose, Days 1, 11, 18, and 25
Title
Potential Relationship Between Changes in SDLP and the Plasma Concentration of Esketamine and Noresketamine
Description
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.
Time Frame
Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)
Title
Effect on Subjective Mental Effort Scale
Description
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.
Time Frame
Part A: Day 2; Part B: Day 1, 11, 18 and 25
Title
Potential Relationship Between Changes in Mean Lateral Position (MLP) and the Plasma Concentration of Esketamine and Noresketamine
Description
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.
Time Frame
Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)
Title
Potential Relationship Between Changes in Mean Speed and the Plasma Concentration of Esketamine and Noresketamine
Description
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.
Time Frame
Part A: 1 hour postdose (Day 1); Part B: 1 hour postdose (Day 11, 18 and 25)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Leiden
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
35212235
Citation
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108228&attachmentIdentifier=d2a59202-2675-439e-a1f3-fe2d4c870cd2&fileName=CR108228_CSR_Synopsis.pdf&versionIdentifier=
Description
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)

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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

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