Abstract
Background OP0201 Nasal Aerosol is a novel drug-device surfactant product being developed for treatment and prevention of otitis media. The active ingredients in OP0201, dipalmitoylphosphatidylcholine (DPPC) and cholesteryl palmitate (CP), are endogenous to the human nasal and respiratory systems. This phase 1 study evaluated the safety and tolerability of OP0201 in healthy adults. Methods This was a randomized, double-blind, placebo-controlled, parallel-group study with a dose-escalation cohort design to evaluate 30 mg/day (Cohort A) and 60 mg/day (Cohort B) of OP0201. Subjects were randomized 4:1 to receive either OP0201 or placebo 3 times per day for 14 consecutive days. Treatment was administered via a metered dose inhaler and sprayed directly backwards into each nostril. Primary endpoints were adverse events, otoscopy, tympanometry, nasal and epipharynx endoscopy, University of Pennsylvania Smell Identification Test (UPSIT), audiology pure-tone hearing test, 12-lead electrocardiography, physical examination, vital signs, and clinical laboratory tests. Exploratory endpoints included baseline-adjusted maximum serum concentration (Cmax) and time to maximum concentration (tmax) of DPPC and CP on Day 14 in Cohort B. Results 101 participants were screened, and 30 were randomized (15 per cohort; n=12 OP0201, n=3 placebo). No deaths, serious adverse events, or treatment-emergent adverse events leading to study discontinuation were reported. No clinically significant deviations from baseline were found in any of the primary endpoints. Serum DPPC and CP concentrations on Day 14 were comparable to baseline in the OP0201 group and numerically higher in the placebo group. Mean baseline-corrected serum DPPC Cmax on Day 14 was 0.82 µg/mL with OP0201 and 4.51 µg/mL with placebo, with a median tmax observed at 0.05 hours for both groups. Mean baseline-corrected serum CP Cmax on Day 14 was 14.89 µM with OP0201 and 89.50 µM with placebo, with a median tmax observed at 0.05 and 0.22 hours for OP0201 and placebo, respectively. Conclusions OP0201 was safe and well tolerated in healthy adults. There were no supraphysiologic systemic concentrations of DPPC or CP after local intranasal administration of a 60 mg/day dose of OP0201. These outcomes support continued development of OP0201 with future studies in a patient population.
The pharmacokinetics of three doses of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler compared with active controls: A Phase I randomized, single-dose, crossover study in healthy adults
