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

A Multi-center, Non-randomized, Open-label, Parallel Study to Evaluate the Pharmacokinetics of Apatinib Mesylate in Subjects With Impaired Renal Function and Healthy Subjects

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.

Study Overview

• Status: Unknown
• Conditions: Subjects With Impaired Renal Function and Healthy Subjects
• Intervention / Treatment: Drug: Apatinib Mesylate

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mild renal impairment	Drug: Apatinib Mesylate; All the subjects will be administrated with 250mg apatinib on day 1
Experimental: moderate remal impairment	Drug: Apatinib Mesylate; All the subjects will be administrated with 250mg apatinib on day 1
Active Comparator: normal renal impairment	Drug: Apatinib Mesylate; All the subjects will be administrated with 250mg apatinib on day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration	0-96 hours
AUC0-t	Area under the plasma concentration versus time curve from zero to 96h	0-96 hours
AUC0-∞	Area under the plasma concentration versus time curve from zero to infinity	0-96 hours

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 5, 2020
• Primary Completion (Anticipated): January 15, 2021
• Study Completion (Anticipated): April 30, 2021

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: HR-APTN-I-011

Drug and device information, study documents

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