P167: Variants in RPAP3 are associated with normal-pressure glaucoma*

or moderate; there was 1 serious AE (gastroenteritis unrelated to the study drug, which occurred during the post-treatment safety follow-up period).Linear PK was observed over the titrated dose range.A one-compartment linear population PK model was developed.Apparent clearance of 1.89 L/h, apparent volume of distribution of 20.2 L, half-life of 7.4 h, and 24-hour steady-state area under the curve (AUC24) of 381 gh/mL were estimated for a child with PMS who weighs 30 kg.All 15 participants who received 13 weeks of treatment with NNZ-2591 had an AUC24 > 300 gh/mL and showed symptomatic improvement on the PMS-anchored Clinical Global Impression-Improvement scale.Exposure projections indicate > 80% of children are expected to achieve the target minimum exposure of 300 gh/mL at a dose of 12 or 13 mg/kg twice daily for children weighing > 20 or 20 kg, respectively.Conclusion: NNZ-2591 appeared safe and well tolerated in children and adolescents with PMS.Both clinicians and caregivers observed improvements in clinically important aspects of PMS, including communication, behavior, cognition/learning, and socialization.The efficacy of NNZ-2591 is supported by exposure-response modeling that shows the target minimum exposure can be achieved with the evaluated dosage.