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

NCT04993404 | Completed Phase 1

• 1 other identifier: ZGJAK021
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Hepatic Insufficiency; Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Participants with Adverse Events (AEs) and Serious AEs

  Screening up to follow-up (7 days after dose administration)

Study Arms (4)

Cohort A：Mild Hepatic Impairment

EXPERIMENTAL

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

Cohort B：Moderate Hepatic Impairment

EXPERIMENTAL

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

Cohort C：Normal Hepatic Function

EXPERIMENTAL

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

Cohort D：Severe Hepatic Impairment

EXPERIMENTAL

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

Interventions

Jaktinib Hydrochloride Tablets DRUG

A single oral dose of 100 mg Jaktinib Hydrochloride Tablets will be administered.

Also known as: Jaktinib

Cohort A：Mild Hepatic Impairment; Cohort B：Moderate Hepatic Impairment; Cohort C：Normal Hepatic Function; Cohort D：Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

Related Publications (1)

• Zhao M, Zhang H, Ma S, Gong S, Wei C, Miao L, Zhao W. Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial. Drug Metab Pharmacokinet. 2024 Dec;59:101030. doi: 10.1016/j.dmpk.2024.101030. Epub 2024 Jul 20.

  PMID: 39442386 DERIVED

MeSH Terms

Conditions

Hepatic Insufficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Liyan Miao, PhD

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

• Weifeng Zhao, PhD

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: August 6, 2021
• Study Start: August 27, 2021
• Primary Completion: September 19, 2022
• Study Completion: September 19, 2022
• Last Updated: January 11, 2024

Record last verified: 2024-01

Locations

CN (1)