RESUMEN
PURPOSE: The objective of this study was to determine the safety and tolerability of pirenzepine ophthalmic gel (PIR) and the magnitude of mydriatic and accommodative effects in myopic children. METHODS: This was a placebo-controlled, parallel double-masked study of unequal (4:1) randomization. Children were randomized to receive 0.5% PIR, b.i.d., or vehicle (placebo) for one week, then titrated to 1% PIR for one week, then 2% PIR for two weeks, and then for an additional 11 months. Enrolled were 26 normal healthy children, 9-12 years old, with myopia (-0.75 to -3 D) and minimal astigmatism (< or =1 D, O.U.). RESULTS: Three of the 26 subjects (all in PIR group) did not complete one year of the study: one child at day 8 who inadvertently received 2.0% PIR as the first concentration, due to accommodative insufficiency, one child for follicular conjunctivitis at 9 months, and one child for administrative reasons at month 1. Other than the child discontinued at day 8, all patients were titrated up to the highest concentration of PIR evaluated. When measured 1 hour after instillation of PIR 0.5%, there was a mean mydriatic effect of less than 1 mm compared to vehicle in either bright or dim light. With increasing concentrations of PIR, this effect became numerically larger, although still remained less than 1 mm in either bright or dim light. Measured approximately 12 hours after instillation, there was little mydriasis within each group (relative to baseline) or between treatments. Similar mild PIR effects were seen on accommodative amplitude. In general, the adverse events reported were mild or moderate in severity, resolved rapidly, and were of the nature and incidence to be expected in a study of a topical anti-muscarinic gel in children of this age. CONCLUSION: The promising efficacy results and acceptable safety profile justifies proceeding with additional clinical trials to evaluate efficacy and further characterize the safety of pirenzepine in a larger patient population.