In this study, tolperisone 150 mg TID did not worse the driving performance as per 3 conditions: (1) driving performance (ie SDLP) was not statistically dissimilar from placebo after dosing on day 1, the morning after the first day of dosing (day 2) or on day 3 at stable state; (2) under all 3 tolperisone dosing conditions, SDLP did not exceed the upper limit of the 95% CI for the effect of alcohol at 0.05% BAC; and (3) symmetry analysis revealed distribution of the paired differences between placebo and tolperisone was not asymmetrical around 0.

This three-way, randomized, blinded, three-period crossover study was aimed to examine the safety and cognitive effects of tolperisone than with placebo and cyclobenzaprine commonly used muscle relaxant.

The study participants were subjected to drug treatments as: tolperisone (150 mg), cyclobenzaprine (10 mg) or placebo 3 thrice daily (TID). They completed a driving test on a validated driving simulator- the Cognitive Research Corporation's Driving Simulator (CRCDS Mini-Sim) on day 1 at the time to extreme plasma concentration, on day 2 before the morning dosage of the drug and on day 3 at steady state after the morning dosage.

Numerous driving parameters and computer-administered digit-symbol substitution test (CogScreen symbol digit coding test) were used to evaluate the participants. The driving setup is a monotonous 100 km highway route on which participants are directed to retain the speed and lane position.

Out of 35 healthy study participants (aged 21 to 55 years), 31 (88.6%) completed the study and received all specified doses of all 3 medicines. Concerning the primary endpoint, the performance of participants who had received tolperisone was not significantly different from those who had received placebo.

On a range of secondary measures evaluating driving ability, cognition and psychomotor performance, participants who had received tolperisone also performed comparably to those with placebo. On the other hand, participants who had received cyclobenzaprine showed significant impairment than placebo on the primary endpoint of the standard deviation of lateral position (SDLP) and on most of the secondary endpoints of driving ability (Figure 1).

Figure 1: Standard deviation of lateral position, SDLP with placebo, tolperisone and cyclobenzaprine on days 1 to 3.

Few reported feeling unsafe to drive on day 1 (10.3%) and day 2 (3.4%) despite their markedly poorer driving performance following cyclobenzaprine. Adverse events incidence was similar for tolperisone (36.4%) and placebo (29.0%) and were greater for cyclobenzaprine (45.4%).

Tolperisone at a dose of 150 mg TID in healthy study participants did not affect various measures of driving, self-reported sleepiness and cognition measures than placebo, on the contrary to those with cyclobenzaprine at a dose of 10 mg TID.