A Study To Test The Effect Of Apatinib On P450 Enzymes

Hengrui Medicine

Status and phase: Unknown; Phase 1

Conditions: Cytochrome P450 Interaction

Treatments: Drug: Warfarin Potassium; Drug: Apatinib; Drug: Nifedipine GTIS

Study type: Interventional

Funder types: Industry

Identifiers

NCT03245307

HR-APTN-DDI-01

Details and patient eligibility

About

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).

Full 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).

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Treament

Experimental group

Description:

In phase A, subjects receiving a single 30 mg oral dose of Nifedipine controlled-release tablets and wash-out for 2 days,a single 3 mg oral dose of warfarin tablets and wash-out for 12 days, then apatinib 750 mg once daily with a single 30 mg oral dose of Nifedipine controlled-release tablets co-administered on day 6 ,a a single 3 mg oral dose of warfarin tablets co-administered on day 9.

Treatment:

Drug: Nifedipine GTIS

Drug: Apatinib

Drug: Warfarin Potassium