Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

Study Overview
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Brief Summary
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The study will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic parameters of pyrotinib in healthy Chinese subjects. The safety of pyrotinib alone and when co-administered with itraconazole will also be assessed.

Official Title
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A Single-centre, Open, Single-dose, Self-control Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: pyrotinib tablet
* Drug: Itraconazole capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions; Able to complete the study as required by the protocol; Subjects have no birth plan and voluntarily take effective contraception from 2 weeks before administration to 3 months after the last dose, and the pre-drug serum HCG test for fertility-enabled women must be negative; Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19   26 kg/m2 ; No clinically significant abnormalities in general physical examination, vital signs, laboratory tests, etc. Exclusion Criteria: Blood donation no less than 400 mL or have blood transfusion within 3 months of dosing. Allergic constitution or known allergy to pyrotinib, itraconazole or the excipients; History of drug abuse in the past 5 years, or positive for drug abuse screening; Alcoholic or often drinkers with drinking amount more than 14 units a week; a heavy smoker; and can't abstain from smoking and alcohol during the study Left ventricular ejection fraction (LVEF) <50% by echocardiography or QTcF ≥ 470 msec by 12 lead electrocardiograph; A clear medical history of important primary organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal system that are not suitable for subjects to participate in the study, as judged by the investigator; Any surgery within 6 months before screening; Have taken hepatotoxic drugs for a long time within 6 months before screening; Subjects who took any clinical trial drugs within 3 months; Subjects who took any drugs that change liver enzymes activity within 28 days before dosing; or took any prescription drugs, over-the-counter drugs or vitamins, health products or herbal medicine within 14 days before dosing; Hepatitis B surface antigen positive, hepatitis C antibody positive, syphilis antibody positive, HIV antibody positive; Subjects who took any beverage or food containing grapefruit, xanthine, caffeine, or alcohol within 48 hours before dosing; strenuous exercise; or other factors which affect drug absorption, distribution, metabolism, excretion, etc.; Other factors that are not suitable for subjects to participate in the study, as judged by the investigator.

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: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Pyrotinib alone and then combined with itraconazole
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pyrotinib alone, pyrotinib + itraconazole<br>Sequential treatments of pyrotinib alone followed by pyrotinib + itraconazole, with a washout period in between. | Drug: pyrotinib tablet<br>* single oral dose of SHR6390 or co-administered with itraconazole<br>Drug: Itraconazole capsule<br>* 200 mg itraconazole QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of pyrotinib | Maximum concentration (Cmax) of pyrotinib | Day 1 and Day 9 | 
| AUC of pyrotinib | Area under the plasma concentration versus time curve of SHR6390 | Day 1 and Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of pyrotinib | Time of maximum concentration of pyrotinib | Day 1 and Day 9 | 
| T1/2 of pyrotinib | Terminal half-life of pyrotinib | Day 1 and Day 9 | 
| AEs and SAEs | Adverse events and serious adverse events | From the first drug administration to 7 days after the last drug administration |