Drug-drug Interaction Study of Gefitinb on Apatinib in NSCLC Patients

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study was to assess the effect of gefitinib on the pharmacokinetics of apatinib mesylate in lung cancer patients. The secondary objective of the study was to assess the pharmacokinetics of gefitinib, and to assess the safety of apatinib mesylate and gefitinib administered in lung cancer patients.

Official Title
-----------------
A Multi-center, Open-label, Fixed-sequence Study of Effect of Gefitinib on the Pharmacokinetics of Apatinib Mesylate in Non-squamous, Non-small-cell Lung Cancer Patients

Conditions
-----------------
NSCLC

Intervention / Treatment
-----------------
* Drug: Apatinib Mesylate, Gefitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-75 years of age. ECOG performance status: level 0 1; Anticipated life expectancy ≥ 12 weeks; Lung cancer patients; Major organs in good function; 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; Able to comprehend and willing to sign an informed consent form (ICF) Exclusion Criteria: History of drug allergy, or allergic to apatinib or gefitinib or ingredients; Squamous cancer, small-cell lung cancer; Symptomatic central nervous system (CNS) metastases Hypertension and couldn't be controlled with medicine; Coagulation disorders; Clinical significant bleeding in 3 months prior dosing; Had surgery in four weeks prior dosing; Disease that affect drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction; Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess in 6 months prior dosing; Urine protein ≥++, and urine protein ≥1.0g in 24 hours; Active infection and need antimicrobial treatments; History of psychiatric substance abuse; Take any clinical trial drugs within four weeks prior dosing; Take any drugs that have effect on gastric acid and metabolic enzyme CYP 3A and CYP2D6; Combined with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or combined with syphilis infection; Addicted to alcohol and tobacco; Take grapefruit or grapefruit product, drinks containing caffeine, xanthine and alcohol in 48 hours prior dosing; The investigator believes that the subjects are not eligible to participate in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: All the subjects will administrated with apatinib and gefitinib following the same sequence to assess the effect of gefitinib on the pharmacokinetics of apatinib in NSCLC patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Subjects will be administrated with 500mg apatinib on day 1 and day 12-15, and administrated with gefitinib on day 4-15. | Drug: Apatinib Mesylate, Gefitinib<br>* Subjects will be administrated with 500mg apatinib on day 1 and day 12-15, and administrated with gefitinib on day 4-15.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum Observed Plasma Concentration for apatinib | 0-24 hours | 
| AUC0-τ | Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 hours | 0-24 hours |