Effects of Tolperisone on Measures of Drowsiness and Cognitive Function

Study Overview
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Brief Summary
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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).

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tolperisone Hydrochloride
* Drug: Cyclobenzaprine Hydrochloride 10 MG
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolperisone 200 mg<br>Study Drug, Tolperisone 200mg TID | Drug: Tolperisone Hydrochloride<br>* Study Drug<br>* Other names: Tolperisone;|
| Experimental: Tolperisone 400 mg<br>Study Drug, Tolperisone 400mg TID | Drug: Tolperisone Hydrochloride<br>* Study Drug<br>* Other names: Tolperisone;|
| Active Comparator: Cyclobenzaprine<br>Active Comparator, Cyclobenzaprine 10mg TID | Drug: Cyclobenzaprine Hydrochloride 10 MG<br>* Active Comparator<br>|
| Placebo Comparator: Placebo<br>Placebo, TID | Other: Placebo<br>* Placebo Comparator<br>|

What is the study measuring?
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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 |