A Study to Evaluate the Relative Bioavailability of Different Strengths of STI-1558 Capsules and the Effect of Strong CYP3A4 Inhibitor (Itraconazole) and Inducer (Rifampin) on the Pharmacokinetics of STI-1558 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- STI-1558
- Conditions
- COVID-19 Pneumonia
- Sponsor
- Zhejiang ACEA Pharmaceutical Co. Ltd.
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Comparison of AUC from time 0 extrapolated to infinity(AUC0-inf ) profiles of two different oral strength of STI-1558 to determine the Relative Bioavailability
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label study. This study includes 2 parts, in which part 1 is a relative BA study, Part 2 is a DDI study. Part 1 and Part 2 could be performed in parallel.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are fully informed of the study and are willing to participate in the study and sign the informed consent document prior to any procedure.
- •Healthy male and female subjects, aged 18 to 45 years (both inclusive).
- •Body mass index (BMI) is between 19 and 24 kg/m2 (both inclusive), and body weight of female subjects ≥ 45 kg, body weight of male subjects ≥ 50 kg.
- •Health status is good, the medical history, vital signs, physical examination, 12- lead ECG, laboratory tests (hematology, blood glucose, blood biochemistry, urinalysis, coagulation test), thyroid function (TSH, FT3, FT4) and serum virology test results are normal or abnormal with no clinical significance (NCS) during the screening period.
- •Female subjects of child-bearing potential must agree to use highly effective contraceptive methods from the screening period to 30 days after the last dose of the study drug, (See Appendix 2 Contraceptive Methods).
- •Male subjects considered fertile must agree to not plan to father a child, not donate sperm, and take effective contraceptive methods from the screening period to 30 days after the last dose of the study drug, (See Appendix 2 Contraceptive Methods).
- •Subjects who are able to communicate well with PI, as well as understand and adhere to the requirements of this study.
Exclusion Criteria
- •Difficulties in venous blood collection or history of dizziness when encountering blood or needles.
- •Known or suspected pregnancy, or breastfeeding.
- •Has a clinically relevant intolerance or allergy to drugs, or are known or suspected to have hypersensitivity to any ingredient in the STI-
- •Only for Part 2: Known or suspected hypersensitivity to any ingredient in formulations of itraconazole and/or rifampicin (See the product label for the relevant information).
- •Has received an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month or 5 times half-life (whichever is longer) before the first dose of study drug.
- •Has a history of gastrointestinal (such as duodenal ulcer, alimentary tract hemorrhage, etc.), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs as determined by the Principal Investigator (PI, or designee).
- •Has a medical history of other significant diseases (including but not limited to respiratory, circulatory, digestive, hematological, endocrinological, immunological, dermatological, mental and nervous systems, facial diseases and other related diseases).
- •Has a major surgery within 3 months before the first dose of the study drug or plans to undergo surgery during the study.
- •Has a history of febrile illness within 14 days before the first dose of the study drug.
- •Has values above the 1.5 × upper limits of normal (ULN) at screening or Day -1 for the following laboratory measures: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or total bilirubin.
Arms & Interventions
Part 1: TR
Subjects will take a single dose of test product 200mg/capsule on Day 1 of the study, then reference product 100mg/capsule on Day 8 of the study.
Intervention: STI-1558
Part 1: RT
Subjects will take a single dose of reference product 100mg/capsule on Day 1 of the study, then test product 200mg/capsule on Day 8 of the study.
Intervention: STI-1558
Part 1: Group 1
Subjects will take a single dose of STI-1558 200mg/capsule on Day 1. Starting from Day 4, subjects will orally take 200mg of itraconazole, q.d, for 6 consecutive days (Day 4 to Day 9). The 5th dose (Day 8) of itraconazole will be co-administered with STI-1558 (200 mg/capsule × 3 capsules) to subjects.
Intervention: STI-1558
Part 1: Group 1
Subjects will take a single dose of STI-1558 200mg/capsule on Day 1. Starting from Day 4, subjects will orally take 200mg of itraconazole, q.d, for 6 consecutive days (Day 4 to Day 9). The 5th dose (Day 8) of itraconazole will be co-administered with STI-1558 (200 mg/capsule × 3 capsules) to subjects.
Intervention: Itraconazole
Part 1: Group 2
Subjects will take a single dose of STI-1558 200mg/capsule on Day 1. Starting from Day 4, subjects will orally take 600mg of rifampin, q.d, for 9 consecutive days (Day 4 to Day 12). The 8th dose (Day 11) of rifampin will be co-administered with STI-1558 (200 mg/capsule × 3 capsules) to subjects.
Intervention: STI-1558
Part 1: Group 2
Subjects will take a single dose of STI-1558 200mg/capsule on Day 1. Starting from Day 4, subjects will orally take 600mg of rifampin, q.d, for 9 consecutive days (Day 4 to Day 12). The 8th dose (Day 11) of rifampin will be co-administered with STI-1558 (200 mg/capsule × 3 capsules) to subjects.
Intervention: Rifampin
Outcomes
Primary Outcomes
Comparison of AUC from time 0 extrapolated to infinity(AUC0-inf ) profiles of two different oral strength of STI-1558 to determine the Relative Bioavailability
Time Frame: Up to 2 weeks.
To compare AUC0-inf of a single 600mg dose of two different oral strength of STI-1558（200 mg/capsule × 3 capsules and 100 mg/capsule × 6 capsules）in healthy adult, human subjects under fasting conditions, to establish relative bioavailability.
To determine the effect of repeat doses of a strong CYP3A4 inhibitor (itraconazole) on the PK of STI-1558 by collecting serum at protocol-specified time points: AUC0-t
Time Frame: Up to 3 weeks.
Comparison of Area Under the Curve (AUC) from time 0 to last time point(AUC0-t) profiles of two different oral strength of STI-1558 to determine the Relative Bioavailability
Time Frame: Up to 2 weeks.
To compare AUC0-t of a single 600mg dose of two different oral strength of STI-1558（200 mg/capsule × 3 capsules and 100 mg/capsule × 6 capsules）in healthy adult, human subjects under fasting conditions, to establish relative bioavailability.
To determine the effect of repeat doses of a strong CYP3A4 inhibitor (itraconazole) on the pharmacokinetics(PK) of STI-1558 by collecting serum at protocol-specified time points: Cmax
Time Frame: Up to 3 weeks.
To determine the effect of repeat doses of a strong CYP3A4 inhibitor (itraconazole) on the PK of STI-1558 by collecting serum at protocol-specified time points: AUC0-inf.
Time Frame: Up to 3 weeks.
To determine the effect of repeat doses of a strong CYP3A4 inducer (rifampin) on the PK of STI-1558 by collecting serum at protocol-specified time points: AUC0-t
Time Frame: Up to 3 weeks.
Comparison of maximum observed concentration(Cmax) profiles of two different oral strength of STI-1558 to determine the Relative Bioavailability
Time Frame: Up to 2 weeks.
To compare Cmax of a single 600mg dose of two different oral strength of STI-1558（200 mg/capsule × 3 capsules and 100 mg/capsule × 6 capsules）in healthy adult, human subjects under fasting conditions, to establish relative bioavailability.
To determine the effect of repeat doses of a strong CYP3A4 inducer (rifampin) on the PK of STI-1558 by collecting serum at protocol-specified time points: Cmax
Time Frame: Up to 3 weeks.
To determine the effect of repeat doses of a strong CYP3A4 inducer (rifampin) on the PK of STI-1558 by collecting serum at protocol-specified time points: AUC0-inf
Time Frame: Up to 3 weeks.
Secondary Outcomes
- Cmax of AC1115(an active metabolite of STI-1558)(Up to 2 weeks for part 1 and 3 weeks for part 2.)
- AUC0-t of AC1115(an active metabolite of STI-1558)(Up to 2 weeks for part 1 and 3 weeks for part 2.)
- AUC0-inf of AC1115(an active metabolite of STI-1558)(Up to 2 weeks for part 1 and 3 weeks for part 2.)