Assessment of Effect of Rapastinel on Driving Performance

Study Overview
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Brief Summary
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Based on the pharmacological class of rapastinel, this study will be conducted to evaluate the participant's driving performance after single IV doses of rapastinel as compared with single oral doses of alprazolam, a benzodiazepine that demonstrates driving impairment, and placebo in healthy participants.

Official Title
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A Phase 1, Randomized, Double-blind, Double-dummy, Placebo-controlled, 5-period, Crossover Study Assessing the Effects of Rapastinel Compared to Alprazolam, Ketamine, and Placebo on Simulated Driving Performance in Normal Healthy Participants

Conditions
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Driving Performance

Intervention / Treatment
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* Drug: Rapastinel
* Drug: Alprazolam
* Drug: Ketamine
* Drug: Rapastinel Matched Placebo
* Drug: Alprazolam Matched Placebo
* Drug: Ketamine Matched Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participant possesses a valid driver's license and is an active driver. Drives a minimum of 5,000 miles (about 8,000 km) per year for the previous 3 years. Participant has a regular sleep pattern, is not engaged in shift-work, and in general, has at least 7 hours of sleep each night (bedtime occurs between 21:00 and 24:00 hours). Exclusion Criteria A history within 2 years of, or current intervention for, a sleeping disorder (including excessive snoring, obstructive sleep apnea) or a chronic painful condition that interferes with the participant's sleep. A history of difficulty in falling asleep or staying asleep in the previous 3 months that is considered clinically significant by the investigator. Participant has traveled across 1 or more time zones (transmeridian travel) in the 14 days before study intervention or is expected to travel across 1 or more time zones during the study. Expected to work on a rotating shift during their participation in the study. Participant works a night shift.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapastinel High Dose<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Rapastinel<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Experimental: Rapastinel Low Dose<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Rapastinel<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Active Comparator: Alprazolam<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Alprazolam<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Active Comparator: Ketamine<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Ketamine<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Placebo Comparator: Placebo for Rapastinel<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Rapastinel Matched Placebo<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Placebo Comparator: Placebo for Alprazolam<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Alprazolam Matched Placebo<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|
| Placebo Comparator: Placebo for Ketamine<br>Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner. | Drug: Ketamine Matched Placebo<br>* Participants will be administered single IV doses of rapastinel, ketamine, rapastinel matched placebo, and ketamine matched placebo, and single oral doses of alprazolam and alprazolam matched placebo in a randomized crossover manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with placebo and positive control (alprazolam) |  | Day 1 of each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with a clinical comparator (ketamine) |  | Day 1 of each intervention | 
| Karolinska Sleepiness Scale (KSS) | The KSS is a participant self-reported measure of situational sleepiness and provides an assessment of alertness/sleepiness. The KSS is a 9-point categorical scale, where 1 = extremely alert and 9 = extremely sleepy-fighting sleep. | Day 1 of each intervention | 
| Self-perceived safety to drive (Right now do you feel safe to drive?) |  | Day 1 of each intervention | 
| Visual Analog Scale to assess participant's motivation and self-appraisal of their driving performance |  | Day 1 of each intervention | 
| CogScreen SDC Test |  | Day 1 of each intervention | 
| Proportion of abnormal lane exceedance events |  | Day 1 of each intervention | 
| Average Speed (mph) |  | Day 1 of each intervention | 
| Total collisions |  | Day 1 of each intervention | 
| Number of exceeded cornering speed threshold events |  | Day 1 of each intervention | 
| Divided attention: average number of correct responses | Participants are asked to answer periodic questions during the driving simulation. | Day 1 of each intervention | 
| Divided attention: average number of errors | Participants are asked to answer periodic questions during the driving simulation. | Day 1 of each intervention | 
| Divided attention: average reaction time |  | Day 1 of each intervention | 
| Rapastinel blood plasma concentration |  | Day 1 of each intervention | 
| Adverse Events |  | Up to 66 days | 
| Proportion of abnormal electrocardiograms |  | Up to 66 days | 
| Columbia-Suicide Severity Rating Scale | The C-SSRS is a clinician-ratedinstrument that reports theseverity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (least severe) to 5 (most severe). | Up to 66 days |