Phase 1 dose-finding study of topical neostigmine ophthalmic solution for alleviating myasthenic ptosis

The study aimed to investigate the safety, optimal biologic dose, and preliminary efficacy of topical neostigmine ophthalmic solution (TNOS) in myasthenia gravis (MG) patients with ptosis. A dose-escalation study comprising cohorts of three patients in each step was performed. The first cohort received 1.5 mg/mL TNOS and was evaluated for safety and efficacy. Then, the subsequent cohorts received the selected dose of TNOS according to the safety and efficacy protocols to determine the optimal biologic dose. Vital signs, visual acuity, intraocular pressure, pupillary size, slit-lamp examinations, and abnormal ocular symptoms were recorded as safety measures. Vertical palpebral fissure and self-reported alleviation of ptosis were investigated as efficacy measures. No systemic or ocular adverse effects were observed in any participant. Vertical palpebral fissure increased by more than 2 mm in 83.3% and 33.3% of patients receiving 1.5 and 1.0 mg/mL TNOS, respectively. The 1.5 mg/mL TNOS significantly increased vertical palpebral fissure from baseline (maximal mean difference 3.30 mm; 95% confidence interval 2.32 to 4.27; p < 0.001). All participants in the 1.5 mg/mL group and 33.3% in the 1.0 mg/mL group reported ptosis alleviation. The 1.5 mg/mL TNOS was considered the optimal biologic dose for alleviating myasthenic ptosis without adverse events.