Pharmacokinetics Of Jaktinib In Subjects With Hepatic Impairment And Normal Hepatic Function

Study To Evaluate The Pharmacokinetics Of Jaktinib Hydrochloride Tablets In Subjects With Hepatic Impairment And Normal Hepatic Function

This multi-center, open-label, parallel-controlled, single-dose Phase 1 study is being conducted to directly characterize the pharmacokinetic (PK) profiles and safety of Jaktinib following administration of a single oral dose in subjects with varying degrees of hepatic impairment compared to healthy matched control subjects with normal hepatic function(matched by age, weight, and sex).

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Healthy Subjects
• Intervention / Treatment: Drug: Jaktinib Hydrochloride Tablets

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital Of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to comprehend and willing to sign an informed consent form. Ability to comply with trial and follow-up procedures.
• Age 18-79 years at the time of signing the ICF, either male or female.
• Male subjects body weight at least 50 kg, and female subjects body weight at least 45 kg. Body mass index (BMI) between 18 and 32 kg/m2 to participate.
• After physical examination, vital signs, laboratory examinations, 12-lead electrocardiogram examination, the investigator determined that it is suitable to participate in this study.
• Subjects are willing to take effective contraceptive measures from screening to 3 months after administration.

Additional Inclusion Criteria for Hepatic Impaired Subjects Only:

• Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment(Requires no use of albumin within 14 days), And it is dysfunction caused by previous primary liver disease.
• Any examination such as B-ultrasound, CT, MRI, FibroScan or liver biopsy confirms the presence of cirrhosis.

Additional Inclusion Criteria for Healthy Subjects Only:

• Have not taken any medicine within 2 weeks before administration; or have stable medication for at least 4 weeks before administration for the treatment of other comorbid diseases.

Exclusion Criteria:

• Drug-induced liver injury.
• Acute liver damage caused by various reasons.
• Patients with liver failure, or combined with dominant hepatic encephalopathy, liver cancer, etc., which the investigator believes are not suitable for participating in the study.
• Patients with a history of massive bleeding from esophageal varices without band ligation, sclerosing agent and TIPS treatment
• Subjects with suspected allergies to Jaktinib or its excipient.
• History of blood donation of 400 mL or more of blood within 3 months prior to screening.
• Drug dependency, a positive urine drug screen.
• Subjects with any significant clinical and laboratory abnormalities which may affect the safety evaluation.
• Subjects suffering from arrhythmia and requiring treatment, or QTcB > 480ms at screening.
• Subjects with clinical symptoms of active bacterial, viral, parasitic or fungal infections requiring treatment at screening.
• Subjects with known human immunodeficiency virus (HIV),
• Subjects with epilepsy or patients who have received psychotropic drug or sedatives during screening.
• Subjects who had experienced malignant tumors within the past 5 years (except for adequately treated local basal cell carcinoma of the skin and cervical carcinoma in situ that have been cured).
• Subjects who have participated in another clinical trial of a new drug or medical instrument within 3 months before screening.
• Females who are breastfeeding or pregnant at Screening.

Exclusion Criteria for Healthy Subjects Only:

• Subjects with hepatitis B surface antigen positive or HCV-RNA positive.
• Patients with a history of liver dysfunction, or physical examination and laboratory examination at screening indicate that there is or may have liver dysfunction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A：Mild Hepatic Impairment; Participants with mild hepatic impairment (Child-Pugh Class A, score of 5 to 6, inclusive) will be administered a single dose of Jaktinib Hydrochloride Tablets.	Drug: Jaktinib Hydrochloride Tablets; A single oral dose of 100 mg Jaktinib Hydrochloride Tablets will be administered.; Other Names: Jaktinib
Experimental: Cohort B：Moderate Hepatic Impairment; Participants with moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9, inclusive) will be administered a single dose of Jaktinib Hydrochloride Tablets.	Drug: Jaktinib Hydrochloride Tablets; A single oral dose of 100 mg Jaktinib Hydrochloride Tablets will be administered.; Other Names: Jaktinib
Experimental: Cohort C：Normal Hepatic Function; Participants with normal hepatic function matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, sex, body mass index) will be administered a single oral dose of Jaktinib Hydrochloride Tablets.	Drug: Jaktinib Hydrochloride Tablets; A single oral dose of 100 mg Jaktinib Hydrochloride Tablets will be administered.; Other Names: Jaktinib
Experimental: Cohort D：Severe Hepatic Impairment; Participants with severe hepatic impairment (Child-Pugh Class C, score of 10 to 11, inclusive) will be administered a single dose of Jaktinib Hydrochloride Tablets.	Drug: Jaktinib Hydrochloride Tablets; A single oral dose of 100 mg Jaktinib Hydrochloride Tablets will be administered.; Other Names: Jaktinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]of Jaktinib and its metabolites（ZG0244 and ZG0245）	AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)	From day 1 to day 3
Maximum Observed Plasma Concentration (Cmax) of Jaktinib and its metabolites（ZG0244 and ZG0245）	To evaluate Maximum Observed Plasma Concentration (Cmax) of Jaktinib and its metabolites（ZG0244 and ZG0245）	From day 1 to day 3
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of Jaktinib and its metabolites（ZG0244 and ZG0245）	The AUC (0-infinity) is the area under the plasma Jaktinib and its metabolites（ZG0244 and ZG0245）concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z)	From day 1 to day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) and Serious AEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening up to follow-up (7 days after dose administration)

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Principal Investigator: liyan Miao, PhD, The First Affiliated Hospital Of Soochow University; Principal Investigator: Weifeng Zhao, PhD, The First Affiliated Hospital Of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Actual): September 19, 2022
• Study Completion (Actual): September 19, 2022

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: ZGJAK021

Drug and device information, study documents

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