Safety, Tolerability, and Systemic Exposure of Apo-Si- K170A-C76 in Healthy Volunteers

Upon signing the informed consent, the subjects underwent a screening period for eligibility evaluation. Subjects were admitted to the Research Unit on Day 1 and eligibility was confirmed again. Eligible subjects, as determined by the Principal Investigator (PI), were randomized as close as possible prior to1st drug administration on Day 1, to receive either intranasal Apo-Si-K170A-C76 or matching placebo. Dosing depended on the cohort the subjects were assigned to. Intranasal (IN) administration was performed to both nostrils of all participants. The nasal spray device contains the Study Drug at 20 mg/mL and delivers 0.1 mL volume per actuation. The subjects received 1-3 actuations per nostril alternately, according to dosing group. Thus, during each administration cohort, dosages registered as dose/nostril are received twice per subject, one dose to each nostril. The study was composed of 7 dosing cohorts. Administration in cohorts 1-5 took place on Day 1. Administration to cohorts 6-7 took place from Day 1 to Day 5. The study drug (or placebo) was administered to both nostrils via intranasal spray, while the subject is seated. All subjects arrived at the clinic for a follow up visit 7±2 days after last day of administration. Cohort 1 involved an initial administration of a single (low) dose of Apo-Si-K170A-C76 (2mg/100μl/nostril, to both nostrils). Cohort 2 involved administration of a single dose of Apo- Si-K170A-C76 at a double dose of the first dose (4mg/200μl/nostril, to both nostrils). Cohort 3 involved administration of a single dose of Apo-Si-K170AC76 at the target dose (x3 of first dose, 6mg/300μl/nostril, to both nostrils). Cohort 4 involved BID administration of the same dose as cohort 2, and cohort 5 involved BID administration of the same dose as cohort 3. All BID dosing was separated by 6 hours. Cohort 6 involved administration of repeated BID doses of Apo-Si-K170A (at the same dose level or lower than that administered in Cohort 4) taken from Day 1 to Day 5. Cohort 7, which aims to reach target dose, involved administration of repeated BID doses of Apo-Si-K170A-C76 (at the same dose level or lower than that administered in Cohort 5) taken also from Day 1 to Day 5.