PSTC100 Study in Healthy Adult Subjects

Official title

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PSTC100 in Healthy Adult Subjects

Overview

This study is a single-center, randomized, double-blind, placebo-controlled, dose-escalation phase I clinical trial designed to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic (PD) characteristics of PSTC100 in healthy adult subjects.

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 employed a randomized, double-blind, placebo-controlled, dose-escalation design to evaluate the safety, tolerability, and PK/PD characteristics of a single dose of 25 mg to 400 mg PSTC100 tablets in healthy adults under fasting conditions.

Part 1 of the study comprises six dose cohorts (A1-A6) with doses of 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg, respectively. Part 1 plans to enroll 46 subjects, with 6 subjects in cohort A1 (4 randomly assigned to the investigational drug and 2 to the placebo) and 8 subjects in each of the other cohorts (6 randomly assigned to the investigational drug and 2 to the placebo).

The MAD part employed a randomized, double-blind, placebo-controlled, and dose-escalation design to evaluate the safety, tolerability, and PK/PD characteristics of once-daily (QD) administration for 7 consecutive days within a dose range of 100 mg to 300 mg PSTC100 tablets in healthy adult subjects.

Part 2 of the study consists of three dose cohorts (A7-A9) with doses of 100 mg, 200 mg, and 300 mg, respectively. Part 2 plans to enroll 24 subjects, with 8 subjects in each cohort (6 randomly assigned to the investigational drug and 2 to the placebo).

Interventions

• Drug PSTC100 tablets
  PSTC100 tablets: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg
• Drug PSTC100 tablets
  100 mg once daily, 200 mg once daily, 300 mg once daily

Primary outcome measures

• Time to Peak 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]
• Peak Concentration (Cmax), [Time frame: 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]
• Area Under the 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]
• Apparent volume of distribution (Vd/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 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 dos]
• 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 peak time (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]

Secondary outcome measures (2)

• Glucose metabolism indicators [Time frame: Pre-dose blood sample, 0.25 hour post-dose, 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 12 hours post-dose, 24 hours, 48 hours, 72 hours post-dose.]
• Lipid metabolism indicators [Time frame: Pre-dose blood sample, 0.25 hour post-dose, 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 12 hours post-dose, 24 hours, 48 hours, 72 hours post-dose.]

Eligibility criteria

Inclusion criteria

• 1.Fully understand the purpose and process of this study, voluntarily participate, and sign an informed consent form;
• 2.At the time of screening, applicants must be between 18 and 55 years old (inclusive), and there are no gender restrictions.
• 3.Body mass index (BMI) is between 18.0 and 32.0 kg/m² (inclusive).
• 4.Male participants should weigh no less than 50 kg, and female participants should weigh no less than 45 kg.
• 5.Based on the medical history, vital signs, physical examination, 12-lead electrocardiogram, laboratory tests (hematology, blood biochemistry, coagulation function, urinalysis), and other examination results, the subjects were in good health and no clinically significant abnormalities were found.
• 6.Female subject has no plans to conceive from the start of the screening period until 40 days after the last dose, and agrees to use contraceptive methods as detailed further in the protocol (see Appendix 11.2) from the time of signing the informed consent form until 40 days after the last dose. Male subject agrees to use contraceptive methods as detailed further in the protocol (see Appendix 11.2) with partners of childbearing potential from the time of signing the informed consent form until 100 days after the last dose.
• 7.Male subjects must agree to refrain from sperm donation from the time of signing the informed consent form until 100 days after the last dose and female subjects must refrain from ova donation from the time of signing the informed consent form until 40 days after the last dose.

Exclusion criteria

• 1.Pregnant women (or those with a positive pregnancy test), or breastfeeding women;
• 2.During the screening and baseline period, the pulse rate ≤ 45 beats/minute or > 100 beats/minute;
• 3.During the screening and baseline period, systolic blood pressure <90 mmHg or ≥140 mmHg, or diastolic blood pressure <50 mmHg or ≥90 mmHg;
• 4.Those who have special dietary requirements and cannot accept the standardized meals provided by the research center;
• 5.Drinking alcohol or consuming beverages rich in fructose (including but not limited to carbonated soft drinks, 100% fruit/pure juice etc.) or energy drinks during the screening and baseline period may affect blood glucose, lipid profile, or muscle metabolism.
• 6.During the screening and baseline period, drinking coffee, consuming St. John's wort, grapefruit, pomelo, cranberry, or engaging in strenuous exercise may affect drug absorption and metabolism.
• 7.A 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; or who have a history of or currently suffer from clinically confirmed cardiovascular, respiratory, digestive, endocrine, metabolic, neurological, dermatological, ophthalmic, infectious, or mental illnesses or abnormalities as per investigator's discretion;
• 8.Suspected or confirmed allergy to any component of the investigational drug, or a confirmed history of severe allergy;
• 9.Previous surgeries that may affect the results of clinical trials (such as cholecystectomy, partial gastrectomy, etc., but subjects with minor surgeries such as removal of superficial lipomas and appendectomy are acceptable).
• 10.Have taken any prescription medications within 14 days prior to screening, or over-the-counter drugs and herbal remedies (except for vitamins and calcium supplements) within 7 days prior to screening. However, use of paracetamol < 2 g per day for less than 7 days is allowed.
• 11.Those who have lost or donated more than 400 mL of blood within the 1 month prior to screening (excluding physiological blood loss);
• 12.Those who have participated in any clinical trials within the 3 months prior to screening (excluding those who failed the screening);
• 13.Those with a history of alcohol abuse: those who have consumed more than 14 standard alcohol units per week in the past 1 year (1 standard alcohol unit is approximately equivalent to 250 mL of 5% ABV beer; or 100 mL of 12.5% ABV wine; or 30 mL of 42% ABV spirits); or those who do not agree to abstain from alcohol during the trial period;
• 14.Those with a history of smoking: averaging ≥5 cigarettes per day in the 3 months prior to screening; or those who do not agree to abstain from smoking during the trial period;
• 15.Those with a history of drug abuse (if a participant engaged in use 3 years ago and is no longer a user, he/she is permitted to be included) or who tested positive for urine drugs abuse test during the screening and baseline period;
• 16.During the screening and baseline period, the breathalyzer test result was >0 mg/100mL;
• 17.During screening, subjects with clinically significant abnormalities in any of the following: Hepatitis B surface antigen, syphilis-specific antibodies, hepatitis C antibodies, or HIV antigen/antibody.
• 18.Any situation that researchers believe poses a safety risk to the subjects or may interfere with the conduct of this study, or any situation that researchers believe the subjects cannot comply with the relevant requirements of this study.

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 Sydney Pty Ltd — Saint Leonards

Identifiers

NCT: NCT07752472 · PSTC100-01-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗