A Study To Test The Effect Of Apatinib On P450 Enzymes

A Single-center, Open-Label, Drug Interaction Study to Determine the Effects of Apatinib on the Metabolism of CYP3A4/5 and CYP2C9 Probe Drugs in Patients With Solid Tumors

Status

UNKNOWN

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03245307

Enrollment

Registered

2017-08-10

Start date

2017-08-22

Completion date

2018-09-30

Last updated

2018-02-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cytochrome P450 Interaction

Brief summary

Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the presence and absence of Apatinib. The probes used included Nifedipine (CYP3A specific), warfarin (CYP2C9 specific).

Detailed description

This open-label study consists of a drug interaction phase that (part A) and a drug-continuation phase (part B). Patients will receive CYP450-probe drugs, and PK assessments will be performed before apatinib-administration and aſter once-daily administration of apatinib for 5 days (the predicted time point when steady-state plasma apatinib concentrations will have been achieved).

Interventions

DRUGApatinib

Apatinib at a dosage of 750mg will be administered daily from day 9 of phase A

DRUGNifedipine GTIS

Nifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A

DRUGWarfarin Potassium

Nifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Histologically or cytologically confirmed diagnosis of advanced solid tumors. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate bone marrow, renal, lung, and liver function. * A female subject must not be pregnant and will agree not to become pregnant during the trial

Exclusion criteria

* Primary carcinoma of liver * Any major surgery, chemotherapy, hormone therapy, investigational drugs, or radiotherapy within the last 28 days. * Poorly controlled hypertension. * A prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities, and corrected QT (QTc) prolongation defined as a QTc interval greater than or equal to 450 msec(male) or 470 msec(female). * Arterial or venous thrombi (including cerebrovascular accident). * Current use of therapeutic anticoagulation (low molecular weight heparin, oral anticoagulant agents). * Active brain metastases. * A history of bleeding problems.

Design outcomes

Primary

Measure	Time frame	Description
Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine	1 year	AUC0\ t of warfarin and nifedipine in the absence or in presence of apatinib will be defined

Secondary

Measure	Time frame	Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Day 1 to 21 ( Phase A）	to assess safety and tolerability of apatinib combined with warfarin or nifedipine in patients with advanced solid tumors. The vital signs, ECG, laboratory values and adverse events (AE and SAE) were judged according to NCI-CTCAE V4.0 criteria

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026