Clinical trial NCT04479891: Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects
Official title: A Single-centre, Open, Single-dose, Self-control Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pyrotinib alone and then combined with itraconazole
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax of pyrotinib
timeFrame: Day 1 and Day 9
measure: AUC of pyrotinib
timeFrame: Day 1 and Day 9
Secondary outcomes:
measure: Tmax of pyrotinib
timeFrame: Day 1 and Day 9
measure: T1/2 of pyrotinib
timeFrame: Day 1 and Day 9
measure: AEs and SAEs
timeFrame: From the first drug administration to 7 days after the last drug administration
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
Study officials:
References: