A Study To Test The Effect Of Apatinib On P450 Enzymes

NCT03245307 | Unknown Phase 1

• 1 other identifier: HR-APTN-DDI-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Cytochrome P450 Interaction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Day 1 to 21 ( Phase A）

Study Arms (1)

Treament

EXPERIMENTAL

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.

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

Interventions

Apatinib DRUG

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

Treament

Nifedipine GTIS DRUG

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

Also known as: Nifedipine

Treament

Warfarin Potassium DRUG

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

Also known as: warfarin

Treament

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Chinese Medical University First Hospital

Shenyang, Liaoning, China

RECRUITING

MeSH Terms

Interventions

apatinib; Nifedipine; Warfarin

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: August 10, 2017
• Study Start: August 22, 2017
• Primary Completion: April 30, 2018
• Study Completion: September 30, 2018
• Last Updated: February 7, 2018

Record last verified: 2017-07

Locations

CN (1)