This is a phase 1, open-label, parallel cohort study to evaluate the PK, safety and tolerability of nebulized ensifentrine following administration of single and multiple doses in healthy Chinese male subjects.
This study consists of two cohorts, and approximately a total of up to 28 healthy male subjects, 14 subjects in Cohort 1, and 14 subjects in Cohort 2, will be enrolled. Cohort 2 will be randomly assigned to Sequence 1 and Sequence 2 according to the ratio of 1:1. Treatment Group 1. Cohort 1: subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID). 2. Cohort 2: subjects will receive two single doses of 1.5 mg and 6 mg ensifentrine, separated by at least a 7-day washout period using crossover design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
14 Subjects enrolled will use one 3 mg/2.5 mL ampule for the 3 mg dose, subjects will receive a 3 mg ensifentrine single dose, followed by 3 mg repeated dose (twice daily, BID). On the dosing day (Day 1), subjects will receive a single dose of 3 mg ensifentrine. On Day 4, subjects will receive multiple doses of 3 mg ensifentrine BID for 3 days (Day 4 to Day 6), and a morning dose will be administered on Day 7.
14 subjects will be enrolled in this cohort, then randomly assigned to one of 2 treatment sequences (6mg and 1.5mg single dose). Subjects will 2 different dose levels of study drug. Two 3 mg/2.5 mL ampules will be needed for the 6 mg dose (5 mL total volume) and the 1.5 mg dose will be achieved using an appropriate dilution protocol described in the pharmacy manual.
The Third Hospital of Changsha
Changsha, Hunan, China
Cmax of RPL554
Blood PK sampling for RPL554 concentration
Time frame: 0 to 72 hours
AUC0-t of RPL554
Area under the plasma concentration from time 0 to the last collection time after drug administration
Time frame: 0 to 72 hours
Tmax of RPL554
Time to maximum observed plasma concentration
Time frame: 0 to 72 hours
t1/2 of RPL554
Half-life of RPL554
Time frame: 0 to 72 hours
Adverse events
Adverse events
Time frame: From the first dose usage to the end of the study, approxiamtely up to 15 days
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