Assessment of Effect of Rapastinel on Driving Performance

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

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.

Study Overview

• Status: Completed
• Conditions: Driving Performance
• Intervention / Treatment: Drug: Rapastinel; Drug: Alprazolam; Drug: Ketamine; Drug: Rapastinel Matched Placebo; Drug: Alprazolam Matched Placebo; Drug: Ketamine Matched Placebo

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Aurora, Ontario, Canada, L4G 0A5
      • Algorithme Pharma
• United States
  • California
    • San Clemente, California, United States, 92673
      • Collaborative Neuroscience Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapastinel High Dose; 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; 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.
Experimental: Rapastinel Low Dose; 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; 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.
Active Comparator: Alprazolam; 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; 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.
Active Comparator: Ketamine; 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; 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.
Placebo Comparator: Placebo for Rapastinel; 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; 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.
Placebo Comparator: Placebo for Alprazolam; 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; 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.
Placebo Comparator: Placebo for Ketamine; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Naurex, Inc, an affiliate of Allergan plc
• Investigators: Study Director: Sheng Fang Su, Allergan

Publications and helpful links

General Publications

• Su S, Kay G, Hochadel T, Rojo J, Christopher Stein J, Boinpally R, Periclou A. A randomized, multicenter trial assessing the effects of rapastinel compared to ketamine, alprazolam, and placebo on simulated driving performance. Clin Transl Sci. 2022 Jan;15(1):255-266. doi: 10.1111/cts.13145. Epub 2021 Nov 7.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): March 29, 2019
• Study Completion (Actual): April 3, 2019

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Alprazolam
• Other Study ID Numbers: RAP-PK-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No