An Open-Label, Parallel, Single-dose, Phase I Clinical Study to Evaluate the Pharmacokinetics and Safety of Orelabrutinib Tablets in Subjects With Varying Degrees of Hepatic Impairment

Beijing InnoCare Pharma Tech Co., Ltd.4 sites in 1 country34 target enrollmentMarch 17, 2023

ConditionsHepatic Impairment

InterventionsOrelabrutinib Tablets

DrugsOrelabrutinib Tablets

Overview

Phase: Phase 1
Intervention: Orelabrutinib Tablets
Conditions: Hepatic Impairment
Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Enrollment: 34
Locations: 4
Primary Endpoint: Area under the concentration-time curve from time 0 to infinity (AUC0-t) (Blood)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an Open-Label, Parallel, Single-dose, Phase I Clinical Study to Evaluate the Pharmacokinetics and Safety of Orelabrutinib Tablets in Subjects with Varying Degrees of Hepatic Impairment

Registry

clinicaltrials.gov

Start Date

March 17, 2023

End Date

December 30, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Beijing InnoCare Pharma Tech Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The subject understands and has provided the informed consent form (ICF);
•Male and female between 18 and 79 years old (inclusive) at the time of signing the ICF;
•Male with weight not less than 50 kg and female not less than 45 kg. Body mass index (BMI): 18-32 kg/m2 (inclusive);
•The subject is suitable to participate in the study as evaluated by the investigator based on physical examination, vital signs, laboratory tests, and 12-lead ECG;
•Within 2 weeks before the study medication, the subject took no prohibited drug (see Appendix 4 for the contraindicated drugs), including any prescription drug, OTC drug, Chinese herbal medicine, or dietary supplement;
•The subject is willing to take effective contraception voluntarily from the screening to 3 months after the dosing of study drug;
•The following criteria apply to the subjects with hepatic impairment:
•Patients with chronic hepatic impairment resulted from viral hepatitis, alcoholic liver disease, autoimmune hepatitis, or other causes. Patients with chronic hepatic impairment are defined as patients with a history of hepatic impairment and stable liver functions for ≥ 1 month based on clinical manifestations. For patients with viral hepatitis, it is imperative to exclude active hepatitis C (if the patient was tested HCV antibody positive, at least 2 tests within 3 months indicating HCV-RNA negative are required) and active hepatitis B (HBV-DNA level should be less than 100 IU/mL with concurrent antiviral treatment); or patients with hepatic cirrhosis confirmed by liver biopsy or other medical imaging (including laparoscopy, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography); or patients with diagnosed hepatic cirrhosis complicated with portal hypertension (allow receiving related portal hypotensives treatments, e.g., carvedilol). Patients who meet any of the above conditions can participate in this study.
•Hepatic impairment of Class A or Class B or Class C based on Child-Pugh system (no albumin should be used within 14 days); and resulted from prior primary liver disease;
•Coagulation functions: INR≤2.5 without intervention of coagulants (2-week washout); hematology: neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 70 g/L, platelet count ≥30 × 109/L; hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN);

Exclusion Criteria

•Drug-induced liver injury;
•Acute hepatic impairment due to various causes;
•Any of the following circumstances: liver transplant recipients; acute or exacerbating hepatic impairment due to various causes; liver failure, complicated with grade 3/4 hepatic encephalopathy; active lesions of hepatic cancer; esophageal and gastric varices hemorrhage; serious/advanced peritoneal or pleural effusion requiring puncture drainage and albumin supplementation; situations deemed not suitable to participate in the study including hepatorenal syndrome;
•Diseases influencing bile excretion within 3 months before the screening, including cholestatic liver disease or biliary tract infection;
•Subjects having portal hypertension with esophageal and gastric varices bleeding within 3 months or subjects having received portal-systemic shunt procedure within half a year, including transjugular intrahepatic portosystemic shunt (TIPS);
•History of significant allergy or intolerance to any drug, food, or other substance;
•Patients with abnormal test value which is clinical significance at screening or before enrollment, that influence the evaluation of safety, including physical examination, vital signs, routine laboratory tests (hematology, blood biochemistry, coagulation function, and urinalysis), 12-lead ECG, and chest CT;
•Any history of serious disease or tother conditions that may influence the study findings, including but not limited to disorders of nervous, cardiovascular, hematologic and lymphatic, immune, renal, gastrointestinal, respiratory, endocrine systems;
•History of surgery that may influence drug absorption, distribution, metabolism, or excretion (e.g., gastroduodenectomy), or proposed possible surgery or scheduled hospitalization during the study;
•Clinical manifestations of bacterial, viral, parasitic, or fungal infection requiring treatment, and coronavirus infection or nucleic acid test positive at screening (excluding hepatitis B) or history of serious active infection within 1 month before the screening;

Arms & Interventions

Orelabrutinib Tablets

Subjects take Single dose of 50 mg orelabrutinib tablet under fasting state

Intervention: Orelabrutinib Tablets

Outcomes

Primary Outcomes

Area under the concentration-time curve from time 0 to infinity (AUC0-t) (Blood)

Time Frame: Blood samples for pharmacokinetics will be taken on Day 1 at pre dose , at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.

Area under the concentration-time curve from time 0 to infinity (AUC0-∞) (Blood)

Time Frame: Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.

Maximum concentration(Cmax) (Blood)

Time Frame: Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.

Secondary Outcomes

Apparent clearance (CL/F) (Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.)
Apparent Volume of Distribution (Vz/F) (Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.)
Area under the unbound drug concentration-time curve (AUCunb) (Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48hours post dose.)
AEs(Through study completion, an average of 1 year)
Time to maximum concentration（Tmax）(Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.)
Half-Life (T1/2) (Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.)
Unbound maximum concentration (Cmax, unb) (Blood)(Blood samples for pharmacokinetics will be taken on Day 1 at pre dose, at 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours post dose.)
SAEs(Through study completion, an average of 1 year)