A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamic Profiles Following Single and Multiple Doses and Food Effect of CS32582 Capsules in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- CS32582 capsule
- Conditions
- Healthy
- Sponsor
- Chipscreen Biosciences, Ltd.
- Enrollment
- 112
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic parameters - Plasma Elimination Half-Life(t1/2)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of CS32582 after single or multiple oral administration, as well as the food effect on the pharmacokinetics in healthy subjects.
Detailed Description
This study consists of 3 parts: single ascending dose (SAD), food effect (FE) and multiple ascending dose (MAD). Both SAD and MAD study are randomized, double-blind, placebo-controlled design. The FE study is a randomized, open-label, two-period, two-crossover design.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy subjects, both male and female.
- •Between18 and 55 years of age (inclusive) at screening visit.
- •BMI between 19.0-26.0 kg/m\^2 (including critical value) at screening visit and baseline visit, male subjects' body weight ≥ 50 kg, female subjects' body weight ≥45 kg.
- •Subject is medically healthy or judged by the investigator to be abnormal but clinically insignificant based on the results of history inquiry, physical examination, vital signs, standard 12-lead electrocardiogram, X-ray, abdominal ultrasound examination, and clinical laboratory tests at the time of screening visit.
- •All subjects and female partners of male agree to use medically recognized effective methods of contraception (including physical contraception, surgical contraception, abstinence, etc.) from the start of signing informed consent form to 3 months after the last dose.
- •Subjects voluntarily participate in the study and sign informed consent form.
Exclusion Criteria
- •History of clinically significant drug allergy or atopic allergic diseases (asthma, urticaria, eczematous dermatitis) or drug allergy to investigational products or similar investigational products.
- •History of cardiovascular system, endocrine system, nervous system, respiratory system, digestive system, liver, kidney, blood and lymphatic system, immune system, psychiatric diseases and metabolic abnormalities.
- •Conditions that may affect the determination of skin adverse events related to the investigational drug, including but not limited to sunburn, excessive tattooing (covering more than 25% of body surface area), or existing acne extending beyond sebum-prone areas (i.e., arms, torso, back, buttocks, and/or genital area).
- •History of myalgia or rhabdomyolysis.
- •History of hereditary hyperbilirubinemia.
- •History of gastrointestinal, hepatic, or renal diseases or surgeries within the past 6 months that could affect drug absorption or metabolism, excluding uncomplicated appendectomy and hernia repair.
- •History of active tuberculosis or positive tuberculosis at the screening visit.
- •History of recurrent bacterial, fungal, or viral infections (≥3 occurrences in the past year, excluding common cold), or active infection requiring treatment at the screening visit, or history of infection within ≤8 weeks before baseline visit requiring intravenous anti-infective drugs and/or hospitalization, or history of infection requiring oral anti-infective drugs ≤2 weeks before baseline visit.
- •Untreated diarrhea at baseline visit or diarrhea symptoms within 7 days before the planned first dose.
- •History of drug abuse.
Arms & Interventions
CS32582 Cohort 1
Subjects receive a single dose of 3 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 3
Subjects receive a single dose of 12 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 1
Subjects receive a single dose of 3 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 2
Subjects receive a single dose of 6 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 2
Subjects receive a single dose of 6 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 3
Subjects receive a single dose of 12 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 4
Subjects receive a single dose of 24 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 4
Subjects receive a single dose of 24 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 5
Subjects receive a single dose of 36 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 5
Subjects receive a single dose of 36 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 6
Subjects receive a single dose of 54 mg CS32582 or matching placebo
Intervention: CS32582 capsule
CS32582 Cohort 6
Subjects receive a single dose of 54 mg CS32582 or matching placebo
Intervention: Placebo capsule
CS32582 Cohort 7
Subjects receive a single dose 12 mg CS32582 in either the fasted or fed state for two periods
Intervention: CS32582 capsule
CS32582 Cohort 8
Subjects receive 3 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: CS32582 capsule
CS32582 Cohort 8
Subjects receive 3 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: Placebo capsule
CS32582 Cohort 9
Subjects receive 6 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: CS32582 capsule
CS32582 Cohort 9
Subjects receive 6 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: Placebo capsule
CS32582 Cohort 10
Subjects receive 12 mg CS32582 or matching placebo for 10 days, once daily from Day 1 to Day 10.
Intervention: CS32582 capsule
CS32582 Cohort 10
Subjects receive 12 mg CS32582 or matching placebo for 10 days, once daily from Day 1 to Day 10.
Intervention: Placebo capsule
CS32582 Cohort 11
Subjects receive 12 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: CS32582 capsule
CS32582 Cohort 11
Subjects receive 12 mg CS32582 or matching placebo for 10 days, twice daily (every 12 h) from Day 1 to Day 9, and once on Day 10.
Intervention: Placebo capsule
Outcomes
Primary Outcomes
Pharmacokinetic parameters - Plasma Elimination Half-Life(t1/2)
Time Frame: From time 0 to 48 hours for single dose. From time 0 to 48 hours after the last dose for multiple doses. From time 0 to 48 hours after each period's dosing for food effect study.
Plasma Elimination Half-Life of CS32582.
Incidence and Severity of Adverse Events (AEs)
Time Frame: From the time of signing the informed consent form to 7 days after the last administration of the drug
To investigate the safety and tolerability by assessment of AEs following administration.
Pharmacokinetic parameters - Peak Plasma Concentration (Cmax)
Time Frame: From time 0 to 48 hours for single dose. From time 0 to 48 hours after the last dose for multiple doses. From time 0 to 48 hours after each period's dosing for food effect study.
Maximum Observed Plasma Concentration of CS32582.
Pharmacokinetic parameters - Area Under the Curve(AUC)
Time Frame: From time 0 to 48 hours for single dose. From time 0 to 48 hours after the last dose for multiple doses. From time 0 to 48 hours after each period's dosing for food effect study.
Area Under the Plasma Concentration-time Curve of CS32582.
Pharmacokinetic parameters - Time of Peak Concentration(Tmax)
Time Frame: From time 0 to 48 hours for single dose. From time 0 to 48 hours after the last dose for multiple doses. From time 0 to 48 hours after each period's dosing for food effect study.
Time to reach maximum observed plasma concentration of CS32582.