Assessment of Effect of Rapastinel on Driving Performance

• ClinicalTrials.gov Identifier: NCT03814733
• Recruitment Status: Completed
• First Posted: January 24, 2019
• Last Update Posted: July 11, 2019
• Sponsor: Naurex, Inc, an affiliate of Allergan plc
• Information provided by (Responsible Party): Naurex, Inc, an affiliate of Allergan plc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Driving Performance	Drug: Rapastinel; Drug: Alprazolam; Drug: Ketamine; Drug: Rapastinel Matched Placebo; Drug: Alprazolam Matched Placebo; Drug: Ketamine Matched Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: November 5, 2018
• Actual Primary Completion Date: March 29, 2019
• Actual Study Completion Date: April 3, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with placebo and positive control (alprazolam) [ Time Frame: Day 1 of each intervention ]

Secondary Outcome Measures :

1. simulated driving performance as measured by SDLP using the CRCDS-MiniSim for rapastinel compared with a clinical comparator (ketamine) [ Time Frame: Day 1 of each intervention ]
2. Karolinska Sleepiness Scale (KSS) [ Time Frame: Day 1 of each intervention ]
   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".
3. Self-perceived safety to drive ("Right now do you feel safe to drive?) [ Time Frame: Day 1 of each intervention ]
4. Visual Analog Scale to assess participant's motivation and self-appraisal of their driving performance [ Time Frame: Day 1 of each intervention ]
5. CogScreen SDC Test [ Time Frame: Day 1 of each intervention ]
6. Proportion of abnormal lane exceedance events [ Time Frame: Day 1 of each intervention ]
7. Average Speed (mph) [ Time Frame: Day 1 of each intervention ]
8. Total collisions [ Time Frame: Day 1 of each intervention ]
9. Number of exceeded cornering speed threshold events [ Time Frame: Day 1 of each intervention ]
10. Divided attention: average number of correct responses [ Time Frame: Day 1 of each intervention ]
    Participants are asked to answer periodic questions during the driving simulation.
11. Divided attention: average number of errors [ Time Frame: Day 1 of each intervention ]
    Participants are asked to answer periodic questions during the driving simulation.
12. Divided attention: average reaction time [ Time Frame: Day 1 of each intervention ]
13. Rapastinel blood plasma concentration [ Time Frame: Day 1 of each intervention ]
14. Adverse Events [ Time Frame: Up to 66 days ]
15. Proportion of abnormal electrocardiograms [ Time Frame: Up to 66 days ]
16. Columbia-Suicide Severity Rating Scale [ Time Frame: Up to 66 days ]
    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).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Collaborative Neuroscience Network

San Clemente, California, United States, 92673

Canada, Ontario

Algorithme Pharma

Aurora, Ontario, Canada, L4G 0A5

Sponsors and Collaborators

Naurex, Inc, an affiliate of Allergan plc

Investigators

• Study Director: Sheng Fang Su; Allergan

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Naurex, Inc, an affiliate of Allergan plc
• ClinicalTrials.gov Identifier: NCT03814733
• Other Study ID Numbers: RAP-PK-18
• First Posted: January 24, 2019
• Last Update Posted: July 11, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ketamine; Alprazolam; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents