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

A Multi-centre, Open-label and Parallel-control Study to Investigate the Pharmacokinetics of Fluzoparib in Healthy Subjects and Those With Impaired Kidney Function

The primary objective is to evaluate pharmacokinetics of Fluzoparib and its main metabolite in subjects with impaired kidney function in comparison with healthy subjects, to develop dose recommendations for patients with renal impairment.

The secondary objective is to evaluate the safety of Fluzoparib in subjects with mild and moderate renal impairment and in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Fluzoparib; Drug: Fluzoparib; Drug: Fluzoparib

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

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • The Second Affiliated Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

-

Inclusion Criteria for subjects with impaired kidney function:

1. Sign the informed consent before the trial, and fully understand the content, process, and possible adverse reactions of the trial;
2. Male or female subjects aged 18 to 70 (including 18 and 70);
3. Body mass index (BMI) ranges from 18 kg/m2 to 28 kg/m2 (including 18 and 28);
4. The glomerular filtration rate should meet the following criteria (GFR, mL/min):Subjects with mild renal impairment (CKD2): 60-89 mL/min (including 60-89);Subjects with moderate renal impairment (CKD3): 30-59 mL/min (including 30-59 ends);
5. Renal function should be stable, and the GFR results should be tested twice before administration (at least 3 days apart) within the same CKD stage.

Inclusion Criteria for subjects with normal kidney function:

1. Sign the informed consent before the trial and fully understand the content, process, and possible adverse reactions of the trial;
2. Male or female subjects aged 18 to 70 (including 18 and 70);
3. Body mass index (BMI) ranges from 18 kg/m2 to 28 kg/m2 (including 18 and 28);
4. Glomerular filtration rate (GFR) ≥90 mL/min.

Exclusion Criteria:

-

Exclusion Criteria for subjects with impaired kidney function:

1. History of kidney transplant;
2. Need Renal dialysis during the study;
3. Urinary incontinence or anuria;
4. Clinically significant heart disease, including but not limited to: congestive heart failure, symptomatic coronary artery disease, myocardial infarction, QTcF≥470 ms (female) or QTcF≥450 ms (male) within 12 months before the start of treatment;
5. Received any investigational drug within 3 months before the study started;
6. Taking any drugs which can affect the metabolic enzyme CYP3A within 14 days before the study started;
7. Smokers and alcoholics, or those screened positive for alcohol;
8. History of drug use, or drug abuse screening positive.

Exclusion Criteria for subjects with normal kidney function:

1. History of kidney transplant;
2. Clinically significant heart disease, including but not limited to: congestive heart failure, symptomatic coronary artery disease, myocardial infarction, QTcF≥470 ms (female) or QTcF≥450 ms (male) within 12 months before the start of treatment;
3. Received any investigational drug within 3 months before the study started;
4. Taking any drugs which can affect the metabolic enzyme CYP3A within 14 days before the study started;
5. Smokers and alcoholics, or those screened positive for alcohol;
6. History of drug use, or drug abuse screening positive.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Drug: Fluzoparib; Normal Renal Function:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Mild Renal Impairment:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Moderate Renal Impairment:A single oral dose of Fluzoparib will be administered.
Experimental: Group B	Drug: Fluzoparib; Normal Renal Function:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Mild Renal Impairment:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Moderate Renal Impairment:A single oral dose of Fluzoparib will be administered.
Experimental: Group C	Drug: Fluzoparib; Normal Renal Function:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Mild Renal Impairment:A single oral dose of Fluzoparib will be administered.; Drug: Fluzoparib; Moderate Renal Impairment:A single oral dose of Fluzoparib will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics parameters of Fluzoparib: Cmax	96 hours post dose
Pharmacokinetics parameters of Fluzoparib: AUC0-t	96 hours post dose
Pharmacokinetics parameters of Fluzoparib: AUC0-∞ (if available)	96 hours post dose
Pharmacokinetics parameters of main metabolite (SHR165202) of Fluzoparib: Cmax	96 hours post dose
Pharmacokinetics parameters of main metabolite (SHR165202) of Fluzoparib: AUC0-t	96 hours post dose
Pharmacokinetics parameters of main metabolite (SHR165202) of Fluzoparib: AUC0-∞ (if available)	96 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Other pharmacokinetics parameters of Fluzoparib: Tmax	96 hours post dose
Other pharmacokinetics parameters of main metabolite (SHR165202) of Fluzoparib: Tmax	96 hours post dose
Plasma protein binding rate of Fluzoparib	Day 01 post dose
Plasma protein binding rate of main metabolite (SHR165202) of Fluzoparib	Day 01 post dose
The incidence and severity of adverse events/serious adverse events (based on NCI-CTCAE 5.0)	19 days

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Actual): December 4, 2023
• Study Completion (Actual): December 5, 2023

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Fluzoparib
• Other Study ID Numbers: SHR3162-I-119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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