Effect of Fluconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the effect of fluconazole on pharmacokinetics of pyrotinib tablet for oral administration in healthy Chinese adult subjects. The secondary objective of the study is to compare the safety of pyrotinib alone and co-administered with fluconazole.

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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Pyrotinib；Fluconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants has given written informed consent with full understanding of the trial content, process and possible adverse reactions; Ability to complete the study as required by the protocol; Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent; Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19   26 kg /m2 (including 19 and 26); Willing to take contraception or male subjects who can guarantee not to donate sperm during the trial and within 6 months after the last dose; female subjects with fertility who did not use contraception for at least 2 weeks before dosing; Exclusion Criteria: Allergic constitution or Allergic to a drug ingredient or component; History of drug use, or drug abuse screening positive; Alcoholic or often drinkers; Left ventricular ejection fraction (LVEF) <50% by echocardiography; 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; Abnormal clinical laboratory tests and clinical significance judged by the investigator or other clinical findings showing the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases; Participated in a clinical trial and has received an investigational product within 3 months prior to the first dosing day in the current study; Positive value of HBsAg、HCV-Ab、HIV-Ab、TPPA at screening； Blood loss ≥400mL within 3 months before first dosing; Patients who had a positive blood pregnancy test and were breastfeeding at the time of screening. The investigators determined that other conditions were inappropriate for participation in this clinical 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
Intervention Model: Single Group Assignment
Interventional Model Description: Pyrotinib alone and then combination with fluconazole
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib/Fluconazole<br>Durg: Pyrotinib Durg: Pyrotinib/Fluconazole Participants received a single oral dose of pyrotinib 80 milligram (mg) on day1 and day9. Participants received a loading dose of fluconazole 400 mg on day6 followed by single dose of fluconazole 200 mg for oral administration from D7 to D18. | Drug: Pyrotinib；Fluconazole<br>* Drug: Pyrotinib Participants received a single oral dose of Pyrotinib tablet on the morning of day1 in treatment period 1. Drug: Pyrotinib/Fluconazole In treatment period 2, Participants received a single oral dose of pyrotinib tablet on the morning of day9, and received a loading dose of fluconazole capsule on day6 followed by single dose of fluconazole for oral administration from D7 to D18.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Pyrotinib |  | Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 168 (Combined with Fluconazole), 240 (Combined with Fluconazole) Hours Post-dose | 
| Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of Pyrotinib |  | Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 168 (Combined with Fluconazole), 240 (Combined with Fluconazole) Hours Post-dose | 
| Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-Inf) of Pyrotinib | AUC0-inf was defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 168 (Combined with Fluconazole), 240 (Combined with Fluconazole) Hours Post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Time Take to Reach Cmax (Tmax) of Pyrotinib |  | Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 168 (Combined with Fluconazole), 240 (Combined with Fluconazole) Hours Post-dose | 
| Elimination Half Life (t1/2) of Pyrotinib | Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. | Pre-dose, and 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 168 (Combined with Fluconazole), 240 (Combined with Fluconazole) Hours Post-dose | 
| The Incidence and Severity of Adverse Events (AEs) or Serious Adverse Events (SAEs) in Participants |  | Baseline up to Day 28 |