## Protocol Section
### Identification Module
**NCT ID:** NCT02919579

**Acronym:** DriveSaFe2

**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

**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)

#### Organization Study ID Info
**ID:** CR108228
#### Organization
**Class:** INDUSTRY
**Full Name:** Janssen Research & Development, LLC
#### Secondary ID Infos
**ID:** 2016-002424-86
**Type:** EUDRACT_NUMBER
**Domain:** Janssen Research & Development, LLC
**ID:** 54135419TRD1019
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2018-06-29

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-04-24

**Type:** ACTUAL

**Last Update Submit Date:** 2019-04-23

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2018-06-29

**Type:** ACTUAL

#### Start Date
**Date:** 2016-10-07

**Type:** ACTUAL

**Status Verified Date:** 2019-04

#### Study First Post Date
**Date:** 2016-09-29
**Type:** ESTIMATED
**Study First Submit Date:** 2016-09-01
**Study First Submit QC Date:** 2016-09-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Janssen Research & Development, LLC

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Depressive Disorder, Major

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 27

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**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.

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 3

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 4

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 5

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 6

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

- Other: Alcohol

- Drug: Placebo (Oral)

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

**Type:** EXPERIMENTAL

#### Arm Group 7

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

**Intervention Names:**

- Drug: Placebo (Intranasal)

- Drug: Esketamine

**Label:** Part B: Placebo+Esketamine

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 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

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

**Name:** Placebo (Intranasal)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 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

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

**Name:** Esketamine

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- 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)

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

**Name:** Alcohol

**Type:** OTHER

#### Intervention 4

**Arm Group Labels:**

- 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)

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

**Name:** Placebo (Oral)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

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

**Measure:** 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

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

**Measure:** 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

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

**Measure:** 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

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

**Measure:** 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

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

**Measure:** 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

#### Secondary Outcomes

**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'.

**Measure:** Effect on Subjective Driving Ability Scale

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

**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).

**Measure:** Karolinska Sleepiness Scale (KSS) Score

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

**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.

**Measure:** 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)

**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.

**Measure:** 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)

**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").

**Measure:** 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

**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.

**Measure:** 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)

**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.

**Measure:** Effect on Subjective Mental Effort Scale

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

**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.

**Measure:** 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)

**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.

**Measure:** 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)

### Eligibility Module

**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

**Maximum Age:** 60 Years

**Minimum Age:** 22 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Leiden

**Country:** Netherlands

#### Overall Officials

**Official 1:**

**Affiliation:** Janssen Research & Development, LLC

**Name:** Janssen Research & Development, LLC Clinical Trial

**Role:** STUDY_DIRECTOR

### References Module

#### References

**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.

**PMID:** 35212235

#### See Also Links

**Label:** 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)

**URL:** https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108228&amp;attachmentIdentifier=d2a59202-2675-439e-a1f3-fe2d4c870cd2&amp;fileName=CR108228_CSR_Synopsis.pdf&amp;versionIdentifier=

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019964

- Term: Mood Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000001526

- Term: Behavioral Symptoms

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7058

- Name: Depression

- Relevance: HIGH

- As Found: Depressive Disorder

- ID: M7061

- Name: Depressive Disorder

- Relevance: HIGH

- As Found: Depressive Disorder

- ID: M7060

- Name: Depressive Disorder, Major

- Relevance: HIGH

- As Found: Depressive Disorder, Major

- ID: M21835

- Name: Mood Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4818

- Name: Behavioral Symptoms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003866

- Term: Depressive Disorder

- ID: D000003863

- Term: Depression

- ID: D000003865

- Term: Depressive Disorder, Major

### Intervention Browse Module - Ancestors

- ID: D000000928

- Term: Antidepressive Agents

- ID: D000011619

- Term: Psychotropic Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

### Intervention Browse Module - Browse Leaves

- ID: M271980

- Name: Esketamine

- Relevance: HIGH

- As Found: Auditory

- ID: M3777

- Name: Ethanol

- Relevance: LOW

- As Found: Unknown

- ID: M4247

- Name: Antidepressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M14474

- Name: Psychotropic Drugs

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000629870

- Term: Esketamine

### Misc Info Module

- Version Holder: 2024-05-24
