Effect of Fluconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Pyrotinib；Fluconazole

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pyrotinib/Fluconazole; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Actual): May 17, 2021
• Study Completion (Actual): May 17, 2021

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: HR-BLTN-DDI-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No