The goal of this Phase 1 clinical trial is to evaluate the safety and pharmacokinetic characteristics of PBK\_M2301 in healthy adult volunteers. The main questions it aims to answer are: What are the maximum concentration (Cmax) and total drug exposure (AUCt) of PBK\_M2301 compared to the combination of two reference drugs? Are there any safety concerns associated with a single oral dose of PBK\_M2301? Researchers will compare PBK\_M2301 with the combination of R1\_PBK\_M2301 and R2\_PBK\_M2301 to assess differences in drug levels. Participants will: Receive each treatment once in a randomized sequence with a one-week washout in between Provide blood samples at multiple time points after dosing Undergo safety assessments including adverse event monitoring, vital signs, laboratory tests, and ECGs
This Phase 1, open-label, randomized, two-period, two-sequence crossover study will evaluate the safety and pharmacokinetic characteristics of PBK\_M2301 in 32 healthy adults. PBK\_M2301 contains levodropropizine 60 mg and Pelargonium sidoides extract 20 mg per tablet. Participants will receive either a single dose of PBK\_M2301 or a combination of two reference drugs (R1\_PBK\_M2301 and R2\_PBK\_M2301) in a randomized sequence, with a one-week washout between treatments. Blood samples will be collected at multiple time points up to 12 hours post-dose to determine plasma concentrations of levodropropizine using a validated LC-MS/MS method. Primary endpoints are Cmax and AUCt, with secondary endpoints including AUC∞, Tmax, t1/2, CL/F, and Vz/F. Safety will be assessed by monitoring adverse events, vital signs, laboratory tests, and ECGs throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
32
A single oral tablet containing levodropropizine 60 mg and Pelargonium sidoides extract (11% ethanol dried extract, 5.5\~6.6→1) 20 mg. Administered after at least 10 hours of fasting with 150 mL of water at room temperature.
A single oral tablet containing levodropropizine 60 mg. Administered after at least 10 hours of fasting with 150 mL of water at room temperature.
A single oral tablet containing Pelargonium sidoides extract (11% ethanol dried extract, 5.5\~6.6→1) 20 mg. Administered after at least 10 hours of fasting with 150 mL of water at room temperature.
H+ Yangji Hospital
Seoul, Seoul, South Korea
RECRUITINGMaximum plasma concentration (Cmax) of Levodropropizine
Cmax will be determined from plasma concentration-time data following single and multiple oral doses of PBK\_M2301, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: Pre-dose (0 hours) to 12 hours post-dose (depending on dosing regimen)
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUCt) of Levodropropizine
AUCt will be calculated using the linear trapezoidal method based on plasma concentration-time data, in accordance with "Regulations on Bioequivalence Tests" (Article 17).
Time frame: Pre-dose (0 hours) to 12 hours post-dose (depending on dosing regimen)
Area under the plasma concentration-time curve extrapolated to infinity (AUC∞) of Levodropropizine
AUC∞ will be derived as the sum of AUCt and the extrapolated terminal area (Ct/λZ) using noncompartmental analysis, following single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: Pre-dose (0 hours) to last quantifiable concentration plus extrapolated terminal phase (up to 12 hours post-dose)
Ratio of AUCt to AUC∞ of Levodropropizine
The percentage of AUCt relative to AUC∞ will be calculated for each participant to assess the proportion of the observed exposure, following single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: Pre-dose (0 hours) to last quantifiable concentration plus extrapolated terminal phase (up to 12 hours post-dose)
Time to reach maximum plasma concentration (Tmax) of Levodropropizine
Tmax will be recorded as the actual observed time of maximum plasma concentration for each participant after single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: Pre-dose (0 hours) to 12 hours post-dose
Terminal elimination half-life (t1/2) of Levodropropizine
t1/2 will be estimated from the terminal slope of the log-linear portion of the plasma concentration-time curve after single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: From Cmax to terminal phase (up to 12 hours post-dose)
Apparent oral clearance (CL/F) of Levodropropizine
CL/F will be calculated as the ratio of dose to AUC∞ using noncompartmental methods, following single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: From dosing to terminal phase (up to 12 hours post-dose)
Apparent volume of distribution (Vz/F) of Levodropropizine
Vz/F will be estimated using noncompartmental analysis based on plasma concentration-time data following single and multiple oral doses of Levodropropizine, administered alone and in combination with R1\_PBK\_M2301 or R2\_PBK\_M2301.
Time frame: From dosing to terminal phase (up to 12 hours post-dose)
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