A Study To Test The Effect Of Apatinib On P450 Enzymes

Cytochrome P450 Interaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03245307
• Other study ID #: HR-APTN-DDI-01
• Status: Recruiting
• Phase: Phase 1
• First received: July 17, 2017
• Last updated: February 6, 2018
• Start date: August 22, 2017
• Est. completion date: September 30, 2018

Study information

• Verified date: July 2017
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cytochrome P450 Interaction

Intervention

Drug:
• Apatinib
Apatinib at a dosage of 750mg will be administered daily from day 9 of phase A
• Nifedipine GTIS
Nifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A
• Warfarin Potassium
Nifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A

Locations

Country	Name	City	State
China	Chinese Medical University First Hospital	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine	AUC0~t of warfarin and nifedipine in the absence or in presence of apatinib will be defined	1 year
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	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	Day 1 to 21 ( Phase A)