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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: HSK36273; Drug: Heparin sodium injection

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult males and females, 18 to 45 years of age (inclusive) at Screening.
2. 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.
3. The subject must be willing and able to provide written informed consent

4. Medically healthy without clinically significant abnormalities at Screening and predose on Day 1, including:

   1. Physical examination without any clinically relevant findings.
   2. 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.
   3. 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.
   4. Normal laboratory tests (hematology, biochemistry, urinalysis, coagulation tests (aPTT and PT).
   5. No clinically significant findings in serum chemistry, hematology, coagulation, and urinalysis tests as deemed by the Investigator.
5. 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.
6. Willing and able to comply with all study evaluations and adhere to protocol schedules and constraints.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Positive test results for active HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies (Abs).
5. Hemoglobin or hematocrit clinically significantly less than lower limits of normal at screening.
6. 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.
7. 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.
8. 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.
9. History of Participating in another investigational clinical trial within 90 days before the first administration of the study drug.
10. Poor venous access that would hamper a 5-day infusion.
11. Positive pregnancy test at screening or check-in (Day -1).
12. 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.
13. Any other factors considered by the investigator to be inappropriate for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and severity of treatment emergent adverse events (TEAEs) .	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	Day1 to Day8

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Phase I; healthy; HSK36273; continuous IV
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: HSK36273-101

Drug and device information, study documents

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