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

Primary Purpose

Healthy, COVID-19

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ASC11 tablets
Placebo
RTV tablets
Sponsored by
Ascletis Pharmaceuticals Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy focused on measuring COVID-19, ASC11, 3CL-pro

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

ASC11 tablets

RTV tablets

Placebo

Arm Description

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)

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)

Part 1 and 2: Subjects will be randomized to receive placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
Title -Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Cmax
Maximum concentration
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Tmax
Time to Maximum Observed Plasma Concentration
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
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: T1/2
Elimination half-life
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: CL/F
Apparent total systemic clearance
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Vz/F
Apparent volume of distribution during the terminal elimination phase
Pharmacokinetics (PK) parameter of ASC11 tablets in Urine: CLR
Renal clearance

Full Information

First Posted
January 6, 2023
Last Updated
February 9, 2023
Sponsor
Ascletis Pharmaceuticals Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05718518
Brief Title
Study to Evaluate Safety, Tolerability, PK and the Food Effect on PK of ASC11/RTV Tablets in Healthy Subjects
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 13, 2023 (Actual)
Primary Completion Date
April 4, 2023 (Anticipated)
Study Completion Date
April 10, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascletis Pharmaceuticals Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, COVID-19
Keywords
COVID-19, ASC11, 3CL-pro

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ASC11 tablets
Arm Type
Experimental
Arm Description
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)
Arm Title
RTV tablets
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1 and 2: Subjects will be randomized to receive placebo
Intervention Type
Drug
Intervention Name(s)
ASC11 tablets
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Part 1 and 2: Subjects will be randomized to receive placebo.
Intervention Type
Drug
Intervention Name(s)
RTV tablets
Intervention Description
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)
Primary Outcome Measure Information:
Title
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) of ASC11 relative to placebo
Description
To evaluate the safety and tolerability of ASC11 tablets combined with Ritonavir tablets in healthy subjects given single and multiple dose increments.
Time Frame
From screening through study completion, up to 14 days
Secondary Outcome Measure Information:
Title
Title Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: AUC 0-inf
Description
Area under the concentration-time curve from the time of dosing extrapolated to time infinity
Time Frame
From screening through study completion, up to 14 days
Title
Title -Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Cmax
Description
Maximum concentration
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Tmax
Description
Time to Maximum Observed Plasma Concentration
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: AUC 0-t
Description
Area under the concentration-time curve from the time of dosing to the last measurable concentration
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: T1/2
Description
Elimination half-life
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: CL/F
Description
Apparent total systemic clearance
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets combined with Ritonavir tablets in Plasma: Vz/F
Description
Apparent volume of distribution during the terminal elimination phase
Time Frame
From screening through study completion, up to 14 days
Title
Pharmacokinetics (PK) parameter of ASC11 tablets in Urine: CLR
Description
Renal clearance
Time Frame
From screening through study completion, up to 14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yunqing Qiu
Phone
+8613588189339
Email
qiuyq@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Liu, master
Phone
+8613958054006
Email
lindaliu87@zju.edu.cn
Facility Information:
Facility Name
The First Affiliated Hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunqing Qiu, Master
Phone
+8613588189339
Email
qiuyq@zju.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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