A Study to Evaluate the Pharmacokinetics of Apatinib in Subjects With Impaired Renal Function

Phase 1

• Conditions: Subjects With Impaired Renal Function and Healthy Subjects
• Interventions: Drug: Apatinib Mesylate

• Registration Number: NCT04414852
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

The primary objective of the study is to compare the pharmacokinetics of apatinib in subjects with impaired renal function and healthy subjects, to give dose recommendations for patients with impaired renal function.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-06
• Study First Submitted: 2020-06-01
• Study First Submitted QC: 2020-06-02
• Last Update Submitted: 2020-06-02
• Study First Posted: 2020-06-04
• Last Update Posted: 2020-06-04
• Study Start: 2020-06-05
• Primary Completion: 2021-01-15
• Study Completion: 2021-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

for subjects with impaired renal function

• Able to comprehend and willing to sign an informed consent form (ICF)
• 18-70 years of age.
• 19 kg/m2<BMI <19-28 kg/m2
• eGFR (MDRD equation) for mild impaired renal function: 60-89 mL/min/1.73 m2 eGFR (MDRD equation) for moderate impaired renal function: 30-59 mL/min/1.73 m2
• In good health, except for kidney disease and complications, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG;
• Agree to take approved method of contraception during the clinical trail and 8 weeks after the last dose of apatinib. Female subject should be negative in the pregnancy test;

for healthy subjects:

• Able to comprehend and willing to sign an informed consent form (ICF)
• 18-70 years of age.
• 19 kg/m2<BMI <19-28 kg/m2
• eGFR (MDRD equation) for mild impaired renal function: ≥90mL/min/1.73 m2
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG;
• Agree to take approved method of contraception during the clinical trail and 8 weeks after the last dose of apatinib. Female subject should be negative in the pregnancy test;

Exclusion Criteria

for subjects with renal impairment

• Renal allograft recipients;
• Need hemodialysis during study;
• Uroclepsia or anuria;
• Allergic to apatinib or ingredients;
• History of heart disease in 12 months before study;
• Coagulation disorders;
• Hypertension and could not be controlled with hypotensor;
• With hepatic or archenteric disease;
• Participate in blood donation within 3 months before screening and donate blood volume ≥400mL, or receive blood transfusion, or donate blood volume≥200mL within 1 month prior dosing.
• Take any clinical trial drugs within 3 months prior dosing;
• Take any drugs that have effect on gastric acid and metabolic enzyme CYP 3A in 14 days before dosing;
• Addicted to alcohol and tobacco, drinking 14 units of alcohol per week (1 unit = 285 mL of beer, or 100mL of wine), or take ≥5 cigarettes;
• Positive in urine drug test;
• Combined with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or combined with syphilis infection;
• Anyone who refuse to stop ingesting drinks containing methylxanthine, or grapefruit or grapefruit-containing products from 48 hours before dosing to the end of the study;
• The investigator believes that the subjects are not eligible to participate in this trial.

for healthy subjects:

• Renal allograft recipients;
• Allergic to apatinib or ingredients;
• History of heart disease in 12 months before study;
• Coagulation disorders;
• Hypertension and could not be controlled with hypotensor;
• With hepatic or archenteric disease;
• Participate in blood donation within 3 months before screening and donate blood volume ≥400mL, or receive blood transfusion, or donate blood volume≥200mL within 1 month prior dosing.
• Take any clinical trial drugs within 3 months prior dosing;
• Take any drugs that have effect on gastric acid and metabolic enzyme CYP 3A in 14 days before dosing;
• Addicted to alcohol and tobacco, drinking 14 units of alcohol per week (1 unit =285 mL of beer, or 100mL of wine), or take ≥5 cigarettes;
• Positive in urine drug test;
• Combined with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or combined with syphilis infection;
• Anyone who refuse to stop ingesting drinks containing methylxanthine, or grapefruit or grapefruit-containing products from 48 hours before dosing to the end of the study;
• The investigator believes that the subjects are not eligible to participate in this trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mild renal impairment	Apatinib Mesylate	-
moderate remal impairment	Apatinib Mesylate	-
normal renal impairment	Apatinib Mesylate	-

Primary Outcome Measures

Name	Time	Method
Cmax	0-96 hours	Maximum plasma concentration
AUC0-∞	0-96 hours	Area under the plasma concentration versus time curve from zero to infinity
AUC0-t	0-96 hours	Area under the plasma concentration versus time curve from zero to 96h