Effects of Tolperisone on Measures of Drowsiness and Cognitive Function

A Randomized, 4-Period, Crossover Study to Investigate the Effects of Tolperisone on Measures of Drowsiness and Cognitive Function Compared to Cyclobenzaprine and Placebo

A Randomized, 4-Period, Crossover Study to characterize the effects of tolperisone 200 mg and 400 mg (supratherapeutic dose) three times a day (TID) over 3 days of dosing on measures of simulated driving performance, cognitive function and drowsiness and compared to placebo and cyclobenzaprine (single-day, residual effect, multiple-day).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: Tolperisone Hydrochloride; Drug: Cyclobenzaprine Hydrochloride 10 MG

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • CNS Trial
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatory male or female, between 21 and 65 years of age, inclusive, for the entire duration of the study (from Screening through Day 3 of last treatment period).
• Body mass index (BMI) range between 18.5 and 30.0 kg/m2, inclusive.
• Subject must possess a valid driver's license and be an active driver and have driven a minimum of 10,000 miles (about 16,000 km) per year for the previous 3 years.
• Subject must demonstrate simulator sickness questionnaire scores that are not indicative of simulator sickness as defined in the driving simulation operations manual.
• Subject must have a regular sleep pattern, not be engaged in shift-work, and in general, have at least 7 hours of sleep each night.

Exclusion Criteria:

• History of sleep disorders, including insomnia, sleep apnea, Restless Legs Syndrome (RLS), or narcolepsy, night-shift workers, routine daytime napping or oversleeping on weekends days (off work) or a score higher than 10 on the Epworth Sleepiness Scale (ESS) at Screening.
• A history of difficulty in falling asleep or staying asleep in the previous 3 months that is considered clinically significant by the Investigator.
• Subject has traveled across 2 or more time zones (trans meridian travel) in the last 2 weeks prior to randomization or is expected to travel across 2 or more time zones during the study.
• Subject has any physical condition (e.g., severe vision issues, hand use limitations) that would prevent the subject from performing the cognitive or drowsiness assessments.
• Subject has a presence or history of any medically diagnosed, clinically significant psychiatric disorder, including depression, anxiety, insomnia, schizophrenia, or bipolar disorder.
• Consumes more than 3 cups of coffee per day.
• Female subjects who are pregnant or lactating.
• Any clinically significant medical abnormality, any clinically significant chronic disease, or any clinically significant finding on physical examination.
• Subject with a genotype status of poor-, ultrarapid-, or indeterminate- metabolizers of cytochrome CYP2D6.
• Subject is unable to remain in the research unit for each of the treatment periods.
• Subject has visual or auditory impairment which in the opinion of the Investigator would interfere with study related procedures or study conduct.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tolperisone 200 mg; Study Drug, Tolperisone 200mg TID	Drug: Tolperisone Hydrochloride; Study Drug; Other Names: Tolperisone
Experimental: Tolperisone 400 mg; Study Drug, Tolperisone 400mg TID	Drug: Tolperisone Hydrochloride; Study Drug; Other Names: Tolperisone
Active Comparator: Cyclobenzaprine; Active Comparator, Cyclobenzaprine 10mg TID	Drug: Cyclobenzaprine Hydrochloride 10 MG; Active Comparator
Placebo Comparator: Placebo; Placebo, TID	Other: Placebo; Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Driving Performance	Standard Deviation of Lateral Position, measured by simulated driving performance using Cognitive Research Corporation Driving Simulator-MiniSim (CRCDS-MiniSim), of tolperisone compared to placebo	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Karolinska Sleepiness Scale	Measure of Drowsiness	Day 1
Epworth Sleepiness Scale	Measure of Drowsiness	Day 3
Reaction Time	Measure of Cognitive Function	Day 1
Rapid Visual Information Processing	Measure of Cognitive Function	Day 1
CogScreen Symbol Digit Coding Test	Measure of Cognitive Function	Day 1

Collaborators and Investigators

• Sponsor: Neurana Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2020
• Primary Completion (Actual): October 16, 2020
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sleepiness; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Tricyclic; Neuromuscular Agents; Muscle Relaxants, Central; Cyclobenzaprine; Tolperisone
• Other Study ID Numbers: CLN-116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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