PSTB100 Study in Healthy Adult Subjects

Official title

A Phase I Clinical Study of Safety, Tolerability, and Pharmacokinetics / Pharmacodynamics of Single and Multiple Ascending Doses of PSTB100 Tablets in Healthy Adult Subjects

Overview

This study is a randomized, double-blind, placebo-controlled, dose-escalation， first-in-human clinical trial in healthy adults, designed to assess the safety, tolerability, and PK characteristics of PSTB100 tablets.

Detailed description

This Phase I clinical trial is a randomized, double-blind, placebo-controlled, dose-escalation study consisting of two parts:

Part1: Single Ascending Dose (SAD) study Part2: Multiple Ascending Dose (MAD) study The SAD part uses a single-center, randomized, double-blind, placebo-controlled, dose-escalation design to evaluate the safety, tolerability, and PK/PD profile of single oral doses of PSTB100 Tablets under fasting conditions in healthy adult subjects.

The MAD part uses a single-center, randomized, double-blind, placebo-controlled, dose-escalation design to evaluate the safety, tolerability, and PK/PD profile of multiple oral doses of PSTB100 Tablets in healthy adults.

In addition, one dose cohort (expected to be Cohort 8) will include assessments of PK/PD changes of PSTB100 in cerebrospinal fluid (CSF) after repeated dosing.

Interventions

• Drug PSTB100 tablets
  PSTB100 tablets: 0.25 mg, 1 mg, 3 mg, 10 mg, 20 mg.
• Drug PSTB100 tablets
  2 mg once daily， 5 mg once daily， 10 mg once daily

Primary outcome measures

• Time to Reach Maximum Observed Plasma concentration (Tmax) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• Maximum Observed PSTB100 Plasma Concentration (Cmax) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• PSTB100 area under the plasma concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞, etc.) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• Plasma clearance (CL/F) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• Plasma elimination half-life (T₁/₂) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• Mean residence time (MRT) [Time frame: Part 1 : Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose Part 2 : Pre- dose to 12 hours, and 24 hours post Day 1 dose to be collected within 15 minutes pre Day 2 dose]
• Steady-state time to peak (Tmax,ss) [Time frame: Pre- dose to 12 hours, 24 hours post day 1 dose, pre- day 4, pre- day 6， pre- day 7 to 24 hours post day 7 dose, 48 hours post day 7 dose.]
• Steady-state peak concentration (Cmax,ss) [Time frame: Pre- dose to 12 hours, 24 hours post day 1 dose, pre- day 4, pre- day 6， pre- day 7 to 24 hours post day 7 dose, 48 hours post day 7 dose.]
• Steady-state trough concentration (Cmin,ss) [Time frame: Pre- dose to 12 hours, 24 hours post day 1 dose, pre- day 4, pre- day 6， pre- day 7 to 24 hours post day 7 dose, 48 hours post day 7 dose.]
• Average steady-state plasma concentration (Cav,ss) [Time frame: Pre- dose to 12 hours, 24 hours post day 1 dose, pre- day 4, pre- day 6， pre- day 7 to 24 hours post day 7 dose, 48 hours post day 7 dose.]

Secondary outcome measures (3)

• Plasma Metabolite Identification [Time frame: Pre- dose to 24 hours , 48 hours post dose, 72 hours post dose]
• Inflammatory Cytokine Markers [Time frame: Pre-dose PD blood sample (before first dose): to be collected within 1 hour pre-dose Pre-dose PD blood sample (before subsequent doses): to be collected within 15 minutes pre-dose]
• Cerebrospinal fluid (CSF) [Time frame: 1 hours post-Day 7 dose, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours post Day 7 dose]

Eligibility criteria

Inclusion criteria

• Healthy subjects aged 18-55 years (inclusive) at screening, with no gender restriction.

Cohort 8 will enroll only male subjects aged 18-45 years (inclusive) at screening.

• Body Mass Index (BMI) of 18.0 to 32.0 kg/m² (inclusive), and 19.0 to 26.0 kg/m² (inclusive) for Cohort 8.
• Good health status confirmed by medical history, vital signs, physical examination, 12-lead ECG, laboratory tests (blood routine, biochemistry, coagulation function, urinalysis), etc., with no clinically significant abnormalities.
• Fully informed about the study, voluntary participation, and signed Informed Consent Form (ICF).
• Women of childbearing potential who have no pregnancy plan from the screening period until 1 month after the end of the trial, and agree to use contraceptive methods as detailed further in the protocol (see Appendix 3) from signing the ICF until 30 days after last dose.
• Males who agree to use contraception as detailed further in the protocol (see Appendix 3) with partners of childbearing potential from signing ICF until 90 days after last dose.

Exclusion criteria

• Females who are pregnant (positive or clinically abnormal pregnancy test result), lactating, or planning to become pregnant.
• Pulse rate ≤50 beats/min or >100 beats/min at screening.
• Systolic blood pressure <90 mmHg or ≥140 mmHg, or diastolic blood pressure <60 mmHg or ≥90 mmHg at screening.
• History or current presence of clinically significant diseases or abnormalities in cardiovascular, respiratory, digestive, endocrine, metabolic, neurological, dermatological, ophthalmological, infectious, or psychiatric systems, including but not limited to history of childhood asthma; history of eczema, no use of steroid creams for 3 months prior to screening; history fully resolved gestational diabetes; current or history of attention deficit hyperactivity disorder (ADHD), anxiety or depression (no use of antidepressants for at least 6 months prior to screening); Gilberts syndrome.

Subjects with previous non-severe diseases or cured acute diseases may be enrolled if the assessor confirms no impact on the clinical trial.

• Use of tobacco, coffee, St. John's wort, grapefruit, grapefruit juice, cranberry juice, or strenuous exercise within 24 hours before enrollment.
• Suspected or confirmed allergy to any ingredient of the investigational product, or any known allergy history.
• Previous surgery that may affect the clinical trial results (including but not limited to cholecystectomy, subtotal gastrectomy; excluding minor surgeries such as subcutaneous lipoma resection).
• Use of any medication within 14 days before the study drug administration, including over-the-counter drugs and herbal medicines (except vitamins and calcium tablets), or dietary supplement within 7 days before the study drug administration.
• Blood loss or blood donation exceeding 400 mL within 30 days before screening (physiological blood loss excluded).
• Participation in any clinical trial of investigational drugs or medical devices within 3 months before screening (excluding subjects who failed screening).
• History of alcohol abuse. Subjects who consumed more than 14 standard alcohol units weekly within the past year (1 standard unit ≈ 250 mL of 5% beer; 100 mL of 12.5% wine; 30 mL of 42% spirits) or who refuse to abstain from alcohol during the trial.
• History of smoking abuse (average ≥ 5 cigarettes daily within 1 month before screening) or refusal to abstain from smoking during the trial.
• History of drug abuse or positive urine drug screening result during screening (subjects with positive cotinine at screening \[D-28\~D-2\] will be not excluded if a negative cotinine is obtained on D-1).
• Breath alcohol test with positive result at screening.
• Clinically abnormal results of HBsAg, anti-HBcAb, anti-TP (if applicable), anti-HCV, anti-HIV, or QuantiFERON Gold.
• History of severe/serious bacterial infection, recurrent (>3× per year) bacterial infections, or herpes simplex virus (HSV) infection.
• Subjects who received live vaccine within 4 weeks of screening, or plan to receive live vaccine during and up to 4 weeks after the last dose of investigational product.
• Subjects for Cohort 8 will be excluded if:

• Experienced cold, infection, etc., within 4 weeks before screening.
• Have contraindications or are unsuitable for lumbar puncture. Any other situation that the researcher considers may bring safety risks to the subject, interfere with the study, or that the subject may not complete the study or comply with the requirements (due to management reasons, dysphagia, or other reasons).

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

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• Nucleus Network Pty Ltd — Brisbane

Identifiers

NCT: NCT07702279 · PSTB100-01-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗