Study to Evaluate Safety, Tolerability, PK and the Food Effect on PK of ASC11/RTV Tablets in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled phase I clinical study evaluating the safety, tolerability, and pharmacokinetics of ASC11 plus ritonavir tablets in healthy subjects and an open-label, cross-over study evaluating the effect of food on the pharmacokinetics of ASC11 plus ritonavir tablets

Official Title
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A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and PK of ASC11/RTV Tablets and Study to Evaluate the Effects of Food on the PK of ASC11/RTV Tablets in Healthy Subjects

Conditions
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Healthy, COVID-19

Intervention / Treatment
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* Drug: ASC11 tablets
* Drug: Placebo
* Drug: RTV tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects aged 18-60 years (including boundary values) If a woman has no planned pregnancy within 6 months after signing the informed consent, and is willing to use effective contraception (e.g. condom, uterine cap, non-hormonal intrauterine device [IUD]) for at least 3 months from the first administration of the study intervention to the last administration of the study intervention; Or not fertile (e.g. surgical sterilization [bilateral oophorectomy, tubal ligation, or hysterectomy] or natural sterilization [continuous > 12 months without menstruation]) If male, agree to use effective contraception throughout the study intervention and for at least 3 months after the last dose of the study intervention, and do not donate sperm. General good health based on history, physical examination (screening and check-in assessment), vital signs and other screening assessments. Able to understand the research content, comply with the research protocol, and voluntarily sign the informed consent. Exclusion Criteria: Pregnant and lactating women. Patients with acute or chronic diseases, including but not limited to cardiovascular, digestive, respiratory, urinary, nervous, endocrine, immune, musculoskeletal, and skin conditions, were judged by the investigator. Any previous or existing hematological disorders or disorders, major liver disease, family history of bleeding/platelet disease. Previous or existing cancer (other than basal cell carcinoma or squamous cell carcinoma of the skin), or hygrosis. Have an autoimmune disease, immunosuppression, or any form of immune deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASC11 tablets<br>Part 1: Subjects will receive ASC11 tablets on single ascending doses with proposed dose levels of ASC11 tablets: 100mg (cohort 1), 200 mg (cohort 2), 400mg (cohort 3) and 800 mg (cohort 4). Part 2: Subjects will receive ASC11tablets 100 to 300 mg (including 3 cohorts) and ASC11 tablets 300 mg(cohort 4) twice daily (BID) for 5 consecutive days and receive a single dose in the early morning of Day 6. Part 3: Subjects will be randomized to receive ASC11 tablets two single 200 mg or 300 mg doses (fed or fasted) | Drug: ASC11 tablets<br>* Part 1: Subjects will receive ASC11 tablets on single ascending doses with proposed dose levels of ASC11 tablets: 100mg (cohort 1), 200 mg (cohort 2), 400mg (cohort 3) and 800 mg (cohort 4). Part 2: Subjects will receive ASC11tablets 100 to 300 mg (including 3 cohorts) and ASC11 tablets 300 mg(cohort 4) twice daily (BID) for 5 consecutive days and receive a single dose in the early morning of Day 6. Part 3: Subjects will be randomized to receive ASC11 tablets two single 200 mg or 300 mg doses (fed or fasted)<br>|
| Experimental: RTV tablets<br>Part 1: Subjects will receive RTV tablets on 100 mg (cohort 1-4). Part 2: Subjects will receive RTV tablets 100 mg (including 3 cohorts) twice daily (BID) for 5 consecutive days and receive a single dose in the early morning of Day 6. Part 3: Subjects will be randomized to receive two single 100 mg doses (fed or fasted) | Drug: RTV tablets<br>* Part 1: Subjects will receive RTV tablets on 100 mg (cohort 1-4). Part 2: Subjects will receive RTV tablets 100 mg (including 3 cohorts) twice daily (BID) for 5 consecutive days and receive a single dose in the early morning of Day 6. Part 3: Subjects will be randomized to receive two single 100 mg doses (fed or fasted)<br>|
| Placebo Comparator: Placebo<br>Part 1 and 2: Subjects will be randomized to receive placebo | Drug: Placebo<br>* Part 1 and 2: Subjects will be randomized to receive placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) of ASC11 relative to placebo | To evaluate the safety and tolerability of ASC11 tablets combined with Ritonavir tablets in healthy subjects given single and multiple dose increments. | From screening through study completion, up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Title Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: AUC 0-inf | Area under the concentration-time curve from the time of dosing extrapolated to time infinity | From screening through study completion, up to 14 days | 
| Title -Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Cmax | Maximum concentration | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Tmax | Time to Maximum Observed Plasma Concentration | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: AUC 0-t | Area under the concentration-time curve from the time of dosing to the last measurable concentration | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: T1/2 | Elimination half-life | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: CL/F | Apparent total systemic clearance | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Vz/F | Apparent volume of distribution during the terminal elimination phase | From screening through study completion, up to 14 days | 
| Pharmacokinetics (PK) parameter of ASC11 tablets in Urine: CLR | Renal clearance | From screening through study completion, up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, ASC11, 3CL-pro