A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of SK-09 in Healthy Adult Participants
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 84
- Locations
- 2
- Primary Endpoint
- Safety Evaluation
Study Overview
Brief Summary
This Phase 1 trial consists of three parts: Part 1 is a Single Ascending Dose (SAD) study, Part 2 is a Multiple Ascending Dose (MAD) study. Both parts adopt a randomized, double-blind, placebo-controlled design. Part 3 is a randomized, open-label, single-dose, two-period crossover self-controlled design FE study.
Detailed Description
Part 1 is a randomized, double-blind, placebo-controlled SAD study to evaluate the safety, tolerability, PK, and PD of single oral doses of SK-09 tablets in healthy adult participants.
Part 2 is a randomized, double-blind, placebo-controlled MAD study designed to evaluate the safety, tolerability, PK, and PD of multiple oral doses of SK-09 tablets in healthy adult participants.
Part 3 is a randomized, open-label, single-dose, two-period crossover self-controlled design FE study to evaluate the food effect on safety, tolerability, and PK of single oral doses of SK-09 tablets in healthy adult participants.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy male and female participants aged 18 to 55 years (inclusive) at the time of screening.
- •Weight and BMI for female and male participants:
- •Body weight ≥ 50 kg; Body mass index (BMI) between 18.5 and 29.9 kg/m2 (inclusive)
- •Participants must be in good general health.
- •Capable of understanding and voluntarily providing written informed consent prior to any study-related procedures.
- •Participants must have no plans for conception during the trial and for 3 months after the last dose, and must voluntarily use effective contraception with no plans for sperm or egg donation .
Exclusion Criteria
- •History or current presence of clinically significant Cardiovascular; Respiratory ; Gastrointestinal; Neurological ; Hematologic/immunologic disorders.
- •Chronic GI conditions requiring daily medication; or history of bariatric surgery.
- •Live/attenuated vaccines within 4 weeks prior to dosing or planned during study.
- •Systolic blood pressure < 90 mmHg or ≥ 140 mmHg, or diastolic blood pressure ≥80 mmHg.
- •History of myocardial infarction, angina, coronary artery bypass grafting, angioplasty, stenting, congestive heart failure, uncontrolled hypotension, unexplained arrhythmia, ventricular tachycardia, atrioventricular block, QT prolongation syndrome, or symptoms/family history of QT prolongation syndrome, as assessed by the investigator to be unsuitable for participation.
- •Positive results for hepatitis B surface antigen, syphilis-specific antibodies, hepatitis C antibodies, or HIV antibodies.
- •Major surgery or trauma requiring hospitalization within 6 months.
- •Hypersensitivity to any component of SK-09 or its excipients.
- •Poor venous access or needle phobia impacting study procedures.
- •History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months.
- •Current smokers unwilling to abstain during study.
- •Participants with ANY of the following abnormalities in clinical laboratory tests at screening and confirmed by a single repeat test, if deemed necessary:
- •AST or ALT level ≥ 1.5×ULN;
- •Total bilirubin level ≥ 1.5×ULN (except Gilbert's with direct bilirubin ≤ ULN)
- •Blood loss or donation exceeding 400 mL within 3 months of dosing.
- •Other investigational product within 30 days of dosing or 5 half-lives (whichever longer).
- •Use of any medications, including over-the-counter drugs, herbal medicine, vitamins, and health supplements, within 2 weeks prior to the first dose or 5 half-lives (whichever longer).
- •Positive pregnancy test or breastfeeding.
- •Unprotected sexual activity within 2 weeks prior to the first dose.
- •Any condition that, in the investigator's opinion, may pose a safety risk to the participant, interfere with the study, or prevent the participant from completing the study or complying with its requirements (due to administrative or other reasons).
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Arms & Interventions
SK-09
Part 1 SAD：Six sequential dose groups will be evaluated, with the planned dose levels as follows: 20 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 500 mg.
Part 2 MAD：Three planned dose groups (low100 mg BID, 200 mg BID, and 500mg QD or 300mg BID/medium/high, based on Part 1 SAD results) will be sequentially evaluated.
Part 3 FE：One planned dose group (150 mg ), 12 participants will be randomized 1:1 to two sequences (Seq 1: AB; Seq 2: BA).
Intervention: SK-09 (Drug)
Placebo
Part 1 SAD：Six sequential dose groups will be evaluated, with the planned dose levels as follows: 20 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 500 mg.
Part 2 MAD：Three planned dose groups (low100 mg BID, 200 mg BID, and 500mg QD or 300mg BID/medium/high, based on Part 1 SAD results) will be sequentially evaluated.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Safety Evaluation
Time Frame: up to 8 days post-dosing for SAD ，up to 14 days post-dosing for MAD， up to 14 days first post-dosing for FE.
Number of participants with AE, with abnormal Vital Signs, abnormal Physical Examination findings, abnormal Laboratory Tests results, abnormal 12-lead ECG readings
Safety Evaluation
Time Frame: up to 8 days post-dosing for SAD and up to 20 days post-dosing for MAD
Number of participants with AE, with abnormal Vital Signs, abnormal Physical Examination findings, abnormal Laboratory Tests results, abnormal 12-lead ECG readings
Secondary Outcomes
- PK Evaluation（Cmax）(up to 72 hours post-dosing for SAD and FE，up to 10 days post-dosing for MAD)
- PK Evaluation（Tmax）(up to 72 hours post-dosing for SAD and FE，up to 10 days post-dosing for MAD)
- PK Evaluation（ AUC0-T）(up to 72 hours post-dosing for SAD and FE，up to 10 days post-dosing for MAD)
- PK Evaluation ( AUC0-∞）(up to 72 hours post-dosing for SAD and FE，up to 10 days post-dosing for MAD)
- PK Evaluation（Tmax）(up to 72 hours post-dosing for SAD and up to 16 days post-dosing for MAD)
- PK Evaluation（Cmax）(up to 72 hours post-dosing for SAD and up to 16 days post-dosing for MAD)
- PK Evaluation（ AUC0-T）(up to 72 hours post-dosing for SAD and up to 16 days post-dosing for MAD)
- PK Evaluation ( AUC0-∞）(up to 72 hours post-dosing for SAD and up to 16 days post-dosing for MAD)
- PD evaluation(up to 12 hour post-dosing on Day 1 for SAD and pending for MAD)