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

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19; Healthy
• Intervention / Treatment: Drug: ASC11 tablets; Drug: RTV tablets; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University school of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASC11 tablets; 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; 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)
Experimental: RTV tablets; 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; 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)
Placebo Comparator: Placebo; Part 1 and 2: Subjects will be randomized to receive placebo	Drug: Placebo; Part 1 and 2: Subjects will be randomized to receive placebo.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ascletis Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2023
• Primary Completion (Actual): April 14, 2023
• Study Completion (Actual): April 14, 2023

Study Registration Dates

• First Submitted: January 6, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Estimated): November 13, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; ASC11; 3CL-pro
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: ASC11-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No