A Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Dosed of HSK36273 in Healthy Volunteers

Sponsor

Haisco Pharmaceutical Group Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT05742126

Collaborator

(none)

Enrollment

Location

Arms

5.2

Actual Duration (Months)

10.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a single-center, Phase 1, placebo and positive-controlled, randomized, partial-blind, integrated, sequential ascending dose / multiple ascending dose study.The safety, tolerability, pharmacokinetics and pharmacodynamics of multiple continuous IV infusion ascending doses of HSK36273 in healthy volunteers will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: HSK36273 Drug: Placebo Drug: Heparin sodium injection	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Other

Official Title:

A Randomized, Partial-Blind, Placebo and Positive-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of HSK36273 in Healthy Subjects.

Actual Study Start Date :

Apr 11, 2022

Actual Primary Completion Date :

Sep 12, 2022

Actual Study Completion Date :

Sep 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HSK36273 Multiple continuous IV infusion ascending doses in cohort 1-5	Drug: HSK36273 Multiple continuous IV infusion ascending doses for 5 days
Placebo Comparator: Placebo 5 cohorts with matching placebo to HSK36273	Drug: Placebo Matching placebo
Active Comparator: Heparin sodium injection Cohort 1-2 with matching positive control to HSK36273	Drug: Heparin sodium injection Matching positive control

Arm

Intervention/Treatment

Experimental: HSK36273

Multiple continuous IV infusion ascending doses in cohort 1-5

Drug: HSK36273

Multiple continuous IV infusion ascending doses for 5 days

Placebo Comparator: Placebo

5 cohorts with matching placebo to HSK36273

Drug: Placebo

Matching placebo

Active Comparator: Heparin sodium injection

Cohort 1-2 with matching positive control to HSK36273

Drug: Heparin sodium injection

Matching positive control

Outcome Measures

Primary Outcome Measures

The number and severity of treatment emergent adverse events (TEAEs) . [Day1 to Day8]
To assess the safety and tolerability of multiple of HSK36273 following 24-hour continuous IV infusions administered over 5 consecutive days with ascending doses in healthy subjects

Secondary Outcome Measures

AUC0-24h [within 1 hour before administration until 24 hours after starting administration]
Area under the drug concentration-time curve, from time 0h to 24h
AUC0-144h [within 1 hour before administration until 144 hours after administration]
Area under the drug concentration-time curve, from time 0h to 144h
Css [within 1 hour before administration until 144 hours after administration]
Steady-State Concentration with a the Initiation of Continuous IV 5-day Infusion of HSK36273
Tss [within 1 hour before administration until 144 hours after administration]
Time to Reach a Steady-State Concentration Following a the Initiation of Continuous IV 5-day Infusion of HSK36273
t1/2 [24 hours after administration]
Apparent terminal half-life
CL [24 hours after administration]
Apparent total clearance of drug
Vd [24 hours after administration]
Apparent volume of distribution
Activated Partial Thromboplastin Time (aPTT) [within 1 hour before administration until 144 hours after administration]
Clotting Biomarker Activated Partial Thromboplastin Time During the Course of a Continuous IV 5-day Infusion of HSK36273
Prothrombin Time (PT) [within 1 hour before administration until 144 hours after administration]
Clotting Biomarker Prothrombin During the Course of a Continuous IV 5-day Infusion of HSK36273
Activated Clotting Time (ACT) [within 1 hour before administration until 144 hours after administration]
Clotting Biomarker Activated Clotting Time During the Course of a Continuous IV 5-day Infusion of HSK36273
FXIa [within 1 hour before administration until 144 hours after administration]
Change from baseline in factor XI activity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adult males and females, 18 to 45 years of age (inclusive) at Screening.
Body Mass Index (BMI) ≥ 18.0 and ≤ 28.0 kg/m2 and a weight of at least 45 kg for female and 50 kg for male.
The subject must be willing and able to provide written informed consent
Medically healthy without clinically significant abnormalities at Screening and predose on Day 1, including:
Physical examination without any clinically relevant findings.
Three conventional 12-ECG recordings (the average of the three measurements will be used to determine eligibility) were consistent with normal cardiac conduction and function.
QT interval corrected using the Fridericia method (QTcF) between 350 to 450 msec for male subjects and 350 to 470 msec for female subjects, inclusive.
Normal laboratory tests (hematology, biochemistry, urinalysis, coagulation tests (aPTT and PT).
No clinically significant findings in serum chemistry, hematology, coagulation, and urinalysis tests as deemed by the Investigator.
Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
Willing and able to comply with all study evaluations and adhere to protocol schedules and constraints.

Exclusion Criteria:

History or presence of major diseases of the cardiovascular, respiratory, digestive, urological, hematologic, endocrine, immunologic, skin or nervous system, as well as any acute illness or surgical procedure within the past 3 months as determined by the investigator to be clinically relevant.
History of abnormal bleeding episodes, e.g. nosebleeds, or abnormally heavy periods, or extensive bleeding after injury, surgery or dental work within 3 months prior to screening.
Any clinically Laboratory tests during the screening period were abnormal and clinically significant as judged by the investigator. Liver function test results (i.e., aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma glutamyl transferase[GGT]) and total bilirubin elevated above the ULN.
Positive test results for active HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies (Abs).
Hemoglobin or hematocrit clinically significantly less than lower limits of normal at screening.
History of drug abuse in the 12 months prior to the first administration of the study drug or alcohol abuse in the 3 months prior.
A clinically significant allergic reaction that the investigator believes interferes with the subject's ability to participate in the trial; Known allergies to any of the study drug ingredients, allergy to anticoagulants or antiplatelet drugs or obvious adverse reactions, allergic to two or more drugs or food, allergic to any ingredient in this product and auxiliary materials.
Donate blood or plasma within 3 months prior to the first administration of the study drug, or lose more than 400mL of whole blood, or receive blood transfusion within 1 year prior to the first administration of the study drug.
History of Participating in another investigational clinical trial within 90 days before the first administration of the study drug.
Poor venous access that would hamper a 5-day infusion.
Positive pregnancy test at screening or check-in (Day -1).
Participation in a clinical trial involving the administration of an investigational or marketed drug within 30 days (90 days for biologics), or five (5) half-lives, whichever is longer, prior to the first dosing or concomitant participation in an investigational study involving no drug administration.
Any other factors considered by the investigator to be inappropriate for participation in the trial.