Effect of Fluconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

Healthy Subjects Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04850651
• Other study ID #: HR-BLTN-DDI-06
• Status: Completed
• Phase: Phase 1
• Start date: April 16, 2021
• Est. completion date: May 17, 2021

Study information

• Verified date: October 2021
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 17, 2021
• Est. primary completion date: May 17, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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 .

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Pyrotinib;Fluconazole
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.

Locations

Country	Name	City	State
China	Jinan Central Hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	The Incidence and Severity of Adverse Events (AEs) or Serious Adverse Events (SAEs) in Participants		Baseline up to Day 28