This is the second single ascending dose study of L608 in healthy participants and is being conducted to evaluate the safety of L608 with dose level ranging from 15 μg to 30 μg.
L608 inhalation Suspension (L608) is developed by Pharmosa Biopharm Inc. (PBI) as a new liposomal Iloprost formulation for inhalation use in the treatment of patients with WHO Group 1 PAH. As a liposomal formulation of iloprost, L608 is intended to reduce the dosing frequency, as well as provide sustained and selective release along with achieving therapeutically relevant iloprost level. Meanwhile, L608 is expected to mitigate burst release related local irritation and systemic side effects (e.g., hypotension due to plasma peak) in clinical practice. This Phase I, randomized, double-blinded, placebo-controlled study will be conducted in healthy participants in New Zealand to evaluate the safety, tolerability, and pharmacokinetic of L608. The dose escalation design is applied in this study. The sentinel dosing design will be applied for all cohorts.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo.
Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo.
NZCR Ltd (New Zealand Clinical Research)
Christchurch, New Zealand
RECRUITINGPercentage of participants with DLT
DLT: Dose-limiting toxicity
Time frame: 7 days after administration
Percentage of participants with TEAEs and SAEs
TEAEs: treatment emergent adverse events; SAEs: serious adverse events
Time frame: 2 weeks after administration
Frequency and severity of TEAEs and SAEs
TEAEs: treatment emergent adverse events; SAEs: serious adverse events
Time frame: 2 weeks after administration
AUC0-t
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration
Time frame: 24 hours after administration
AUC0-inf
Area under the plasma concentration-time curve from time 0 to infinity
Time frame: 24 hours after administration
%AUCextrap
AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC
Time frame: 24 hours after administration
Cmax
Maximum observed plasma concentration
Time frame: 24 hours after administration
Tmax
Time to reach the maximum observed plasma concentration
Time frame: 24 hours after administration
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T1/2
Apparent plasma terminal elimination half-life
Time frame: 24 hours after administration
CL/F
Apparent total plasma clearance
Time frame: 24 hours after administration
Vz/F
Apparent volume of distribution during the terminal phase
Time frame: 24 hours after administration
λz
Terminal elimination rate constant
Time frame: 24 hours after administration
Cmax/D
Dose-normalized Cmax.
Time frame: 24 hours after administration
AUC0-t/D
Dose-normalized AUC0-t.
Time frame: 24 hours after administration
AUC0-inf/D
Dose-normalized AUC0-inf.
Time frame: 24 hours after administration