A Food Effect Study of Apatinib Mesylate in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective of the study was to assess the effect of high-fat and low-fat meal on the pharmacokinetics of apatinib mesylate in Chinese adult healthy subjects. The secondary objective of the study was to assess the safety of apatinib mesylate administered in adult healthy subjects.

Official Title
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A Randomized, Open-label, Single Dose, Three-period, Six-sequences, Crossover Study of High-fat and Low-fat Meal Effect on the Pharmacokinetics of Apatinib Mesylate in Chinese Healthy Adult Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Apatinib Mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-45 years of age, male or female, each gender should be more than 1/4 of the whole sample size. The weight of male subject ≥50kg, weight of female subject ≥45kg, 19≤BMI≤28kg/m2 In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG; 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 ingredients; Drinking 14 units of alcohol per week within 6 months prior dosing(1 unit = 360 mL of beer, or 150mL of wine) ; Take any prescription or traditional Chinese medicines within four weeks prior dosing; take any over-the-counter medication, vitamin products within two weeks before dosing; Take any clinical trial drugs within 3 months prior dosing; Participate in blood donation within 3 months before screening and donate blood volume ≥400mL or blood loss ≥400mL, or receive blood transfusion; or donate blood volume≥200mL or blood loss ≥200mL within 1 month prior dosing. Combined with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or combined with syphilis infection; Anyone who refuse to stop ingest foods or drinks containing caffeine, xanthine or alcohol from 48 hours before dosing to the end of the study; Anyone who refuse to stop ingesting grapefruit or grapefruit-containing products from 7 days before dosing to the end of the study; The investigator believes that the subjects are not eligible to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after fasted, the second dose will be after low-fat meal, the third dose will be after high-fat meal | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|
| Experimental: Arm 2<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after high-fat meal, the second dose will be after fasted, the third dose will be after low-fat meal | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|
| Experimental: Arm 3<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after low-fat meal, the second dose will be after high-fat meal, the third dose will be after fasted | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|
| Experimental: Arm 4<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after fasted, the second dose will be after high-fat meal, the third dose will be after low-fat meal | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|
| Experimental: Arm 5<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after low-fat meal, the second dose will be after fasted, the third dose will be after high-fat meal | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|
| Experimental: Arm 6<br>Drug:apatinib mesylate tablet , 250 mg, 3 discrete single doses separated by 4-days: the first dose will be after high-fat meal, the second dose will be after low-fat meal, the third dose will be after fasted | Drug: Apatinib Mesylate<br>* Single dose of apatinib mesylate after high-fat meal, low fat meal and fast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum Observed Plasma Concentration for apatinib [ Time Frame: Day 1: 0-72 hours; Day5: 0-72 hours;Day9:0-72hours ] | Time Frame: Day 1: 0-72 hours; Day5: 0-72 hours;Day9:0-72hours | 
| AUC0-t | Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for apatinib | Time Frame: Day 1: 0-72 hours; Day5: 0-72 hours;Day9:0-72hours | 
| AUC0-inf | Area Under the Plasma Concentration-time Curve from Time 0 to Infinite Time for apatinib | Time Frame: Day 1: 0-72 hours; Day5: 0-72 hours;Day9:0-72hours |