Clinical relevance: Patients prescribed pilocarpine ophthalmic solution are advised to be cautious when driving at night, but studies evaluating the effects of pilocarpine hydrochloride ophthalmic solution 1.25% (pilo), approved to treat presbyopia, on driving at night are lacking.
Background: This double-masked, crossover, phase 3b study evaluated night-driving performance with pilo or the placebo once daily.
Methods: Forty-three adults (40-55 years) with presbyopia impacting daily activities and mesopic, high-contrast, binocular distance-corrected near vision 6/12-6/30 were randomised to bilateral treatment with pilo followed by placebo or placebo followed by pilo (with a ≥7-day washout between interventions). Night-driving performance was evaluated at twilight at a closed-circuit course. Primary efficacy endpoint: overall composite night-driving performance Z score at the end of the 7-14-day intervention period, 1 hour post-instillation. Pilo was considered non-inferior if the lower limit of the 95% confidence interval (CI) for the least squares mean difference (LSMD, pilo minus placebo) was >-0.25. Other efficacy endpoints: individual components of the night-driving performance test (hazard avoidance rate; road sign recognition rate and distance; pedestrians recognition distance; overall driving and lane-keeping times) and night-driving experience questionnaire. Safety included treatment-emergent adverse events (TEAEs).
Results: The mean overall composite Z scores were -0.121 (pilo) and 0.118 (placebo). The LSMD (pilo minus placebo) was -0.224 (95% CI, -0.346, -0.103), with 3 of the 7 individual tasks being significantly better with the placebo. The questionnaire did not reveal significant differences between pilo and the placebo. There were no serious or severe TEAEs and no TEAE-related discontinuations. The most common ocular TEAEs were headache and visual impairment with pilo (both 27.9%), and dry eye (7.0%) with the placebo.
Conclusion: The overall performance of night driving was inferior with pilo, compared with placebo. The study findings are consistent with the current class labelling and provide evidence to inform regulators and assist clinicians considering prescribing pilo to adults who seek treatment of presbyopia symptoms and drive at night.ClinicalTrials.gov identifier: NCT04837482.
Keywords: Near vision; pilocarpine; presbyopia; randomised controlled trial.