Evaluation of the Pharmacokinetics of "PBK_M2301" in Healthy Adults

Official title

A Phase 1 Clinical Trial to Evaluate the Pharmacokinetic Characteristics of "PBK_M2301" in Healthy Adult Volunteers

Overview

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

Detailed description

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.

Interventions

• Drug PBK_M2301 (levodropropizine + Pelargonium sidoides extract)
  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.
• Drug R1_PBK_M2301 (levodropropizine)
  A single oral tablet containing levodropropizine 60 mg. Administered after at least 10 hours of fasting with 150 mL of water at room temperature.
• Drug R2_PBK_M2301 (Pelargonium sidoides extract)
  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.

Primary outcome measures

• Maximum plasma concentration (Cmax) of Levodropropizine [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 [Time frame: Pre-dose (0 hours) to 12 hours post-dose (depending on dosing regimen)]

Secondary outcome measures (6)

• Area under the plasma concentration-time curve extrapolated to infinity (AUC∞) of Levodropropizine [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 [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 [Time frame: Pre-dose (0 hours) to 12 hours post-dose]
• Terminal elimination half-life (t1/2) of Levodropropizine [Time frame: From Cmax to terminal phase (up to 12 hours post-dose)]
• Apparent oral clearance (CL/F) of Levodropropizine [Time frame: From dosing to terminal phase (up to 12 hours post-dose)]
• Apparent volume of distribution (Vz/F) of Levodropropizine [Time frame: From dosing to terminal phase (up to 12 hours post-dose)]

Eligibility criteria

1 Inclusion Criteria

Subjects who meet all of the following criteria may be included in the study:

• Male or female subjects aged 19 years or older and less than 65 years at the time of screening.
• Body mass index (BMI) between 18 and 30 kg/m² (inclusive) at screening (BMI = weight (kg) / height (m)²):

• For male subjects: body weight ≥ 50 kg.
• For female subjects: body weight ≥ 45 kg.
• No clinically significant congenital or chronic diseases, and no pathological symptoms or findings based on internal medicine examination (including, if necessary, electroencephalography, electrocardiography, chest and/or upper gastrointestinal endoscopy, or gastrointestinal radiographic examination).
• Judged by the principal investigator (or a sub-investigator) to be suitable for participation based on diagnostic tests performed according to the characteristics of the investigational product, including hematology, clinical chemistry, coagulation, serology, urinalysis, and electrocardiography (ECG).
• Voluntarily decides to participate after receiving and fully understanding a detailed explanation of the study, and signs the written informed consent form, agreeing to comply with the study requirements during the study period.
• Agrees to use medically acceptable contraception\* (excluding hormonal contraceptives) from the first administration of the investigational product until 1 week after the last administration, to prevent pregnancy in themselves or their spouse/partner, and agrees not to donate sperm or ova during this period.

• Medically acceptable contraception: intrauterine device (IUD), intrauterine system (IUS), vasectomy, tubal ligation, or a combination of barrier methods (male condom, female condom, cervical cap, diaphragm, contraceptive sponge). When using spermicide, at least two barrier methods should be used in combination.

2 Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

• Use of enzyme-inducing or enzyme-inhibiting drugs such as barbiturates within 30 days prior to the first administration, or use of any drugs that may interfere with the study within 10 days prior to the first administration.
• Participation in a bioequivalence study or any other clinical trial and administration of an investigational product within 6 months prior to the first administration in this study.
• Whole blood donation within 8 weeks, component blood donation within 2 weeks, or receipt of a blood transfusion within 4 weeks prior to the first administration in this study.
• History of gastrointestinal resection surgery that may affect drug absorption (excluding appendectomy or hernia repair).
• Within 1 month prior to the first administration:

• For male subjects: average alcohol consumption > 21 units/week.
• For female subjects: average alcohol consumption > 14 units/week.

(1 unit = 50 mL soju, 250 mL beer, or 30 mL whisky)

• Average smoking > 20 cigarettes/day.
• Presence of the following conditions:

• Known hypersensitivity to the investigational product or any of its components.
• Bronchial hypersecretion.
• Mucociliary dysfunction (e.g., Kartagener syndrome, primary ciliary dyskinesia).
• Increased bleeding tendency or use of anticoagulant therapy.
• Severe hepatic impairment.
• Severe liver disease or severe renal disease.
• Hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• History of clinically significant psychiatric disorders.
• Any other reason, not specified in the inclusion/exclusion criteria, that in the opinion of the principal investigator (or a sub-investigator) makes the subject unsuitable for participation.
• For female subjects: pregnant, suspected of being pregnant, or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Basic science

Study locations

South Korea · 1 center

• H+ Yangji Hospital — Seoul

Identifiers

NCT: NCT07161180 · PBK_M2301_102 · PBK_M2301_102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗