Clinical trial NCT04850651: Effect of Fluconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-20
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 combination with fluconazole
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Participants has given written informed consent with full understanding of the trial content, process and possible adverse reactions;
2. Ability to complete the study as required by the protocol;
3. Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
4. 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);
5. 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:

1. Allergic constitution or Allergic to a drug ingredient or component;
2. History of drug use, or drug abuse screening positive;
3. Alcoholic or often drinkers;
4. Left ventricular ejection fraction (LVEF) \<50% by echocardiography;
5. 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;
6. 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;
7. Participated in a clinical trial and has received an investigational product within 3 months prior to the first dosing day in the current study;
8. Positive value of HBsAg、HCV-Ab、HIV-Ab、TPPA at screening；
9. Blood loss ≥400mL within 3 months before first dosing;
10. Patients who had a positive blood pregnancy test and were breastfeeding at the time of screening.
11. The investigators determined that other conditions were inappropriate for participation in this clinical trial .

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Pyrotinib
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of Pyrotinib
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-Inf) of Pyrotinib
timeFrame: 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 outcomes:
measure: The Time Take to Reach Cmax (Tmax) of Pyrotinib
timeFrame: 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
measure: Elimination Half Life (t1/2) of Pyrotinib
timeFrame: 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
measure: The Incidence and Severity of Adverse Events (AEs) or Serious Adverse Events (SAEs) in Participants
timeFrame: Baseline up to Day 28
Other outcomes:
Locations:
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
Study officials:
References: