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

Zelgen Biopharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects; Hepatic Insufficiency

Treatments: Drug: Jaktinib Hydrochloride Tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT04993404

ZGJAK021

Details and patient eligibility

About

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).

Enrollment: 24 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

Cohort A：Mild Hepatic Impairment

Experimental group

Description:

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.

Treatment:

Drug: Jaktinib Hydrochloride Tablets

Cohort B：Moderate Hepatic Impairment

Experimental group

Description:

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.

Treatment:

Drug: Jaktinib Hydrochloride Tablets

Cohort C：Normal Hepatic Function

Experimental group

Description:

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.

Treatment:

Drug: Jaktinib Hydrochloride Tablets

Cohort D：Severe Hepatic Impairment

Experimental group

Description:

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.

Treatment:

Drug: Jaktinib Hydrochloride Tablets