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).

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.