Safety and Pharmacokinetics of Fluzoparib in Healthy Subjects and Those With Impaired Liver Function

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and pharmacokinetics of Fluzoparib in subjects with impaired liver function in comparison with healthy subjects ,to develop dose recommendations for patients with hepatic impairment.

Official Title
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A Open, Single-dose, Parallel-control Study to Investigate the Pharmacokinetics of Fluzoparib in Healthy Subjects and Those With Impaired Liver Function.

Conditions
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Hepatic Impairment, Healthy Subjects

Intervention / Treatment
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* Drug: Fluzoparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for subjects with impaired liver function: Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions; Ability to complete the study as required by the protocol; Healthy male or female subjects aged 18 to 65 (including 18 and 45) at the date of signing the informed consent; Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19   29kg /m2 (including 19 and 29); Participants with alcoholic liver disease, autoimmune liver disease, Non-Alcoholic Liver Diseases and inherited metabolic liver disease. Mild Hepatic Impairment group should be stable≥28days ; Moderate Hepatic Impairment group should be stable≥14days. Exclusion Criteria impaired liver function: Allergic constitution; History of drug use, or drug abuse screening positive; Alcoholic or often drinkers; Received any surgery in the previous 6 months before screen phase; A clear medical history of important primary organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal sysem. Abnormal clinical laboratory tests and clinical significance judged by the investigator or other clinical findings showing the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases. Patients with hepatic encephalopathy; Taking any drugs which affects the metabolic enzyme CYP3A within 14 days before the study started, Inclusion Criteria for subjects with normal liver function: Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions; Ability to complete the study as required by the protocol; Healthy male or female subjects aged 18 to 65 (including 18 and 45) at the date of signing the informed consent;The age and gender should match with impaired liver function; Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19   29kg /m2 (including 19 and 29); The body weight should match with impaired liver function. Exclusion Criteria normal liver function: Allergic constitution; History of drug use, or drug abuse screening positive; Alcoholic or often drinkers; Received any surgery in the previous 6 months before screen phase; A clear medical history of important primary organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal sysem. Abnormal clinical laboratory tests and clinical significance judged by the investigator or other clinical findings showing the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases. Taking any drugs which affects the metabolic enzyme CYP3A within 14 days before the study started,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal Hepatic Function<br> | Drug: Fluzoparib<br>* A single oral dose of 50 mg Fluzoparib will be administered.<br>|
| Experimental: Mild Hepatic Impairment<br> | Drug: Fluzoparib<br>* A single oral dose of 50 mg Fluzoparib will be administered.<br>|
| Experimental: Moderate Hepatic Impairment<br> | Drug: Fluzoparib<br>* A single oral dose of 50 mg Fluzoparib will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameters of Fluzoparib: Cmax |  | through study completion, an averange of half year | 
| Pharmacokinetics parameters of Fluzoparib: AUC0-t |  | through study completion, an averange of half year | 
| Pharmacokinetics parameters of Fluzoparib: AUC0-∞(if available) |  | through study completion, an averange of half year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other pharmacokinetics parameters of Fluzoparib: Tmax |  | through study completion, an averange of half year | 
| plasma protein binding rate of Fluzoparib |  | through study completion, an averange of half year | 
| The incidence and severity of adverse events/serious adverse events (based on NCI-CTCAE 5.0) |  | through study completion, an averange of half year | 
| Other pharmacokinetics parameters of Fluzoparib: T1/2 etc. |  | through study completion, an averange of half year |