Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

A Single-centre, Open, Single-dose, Self-control Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: pyrotinib tablet; Drug: Itraconazole capsule

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

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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 alone, pyrotinib + itraconazole; Sequential treatments of pyrotinib alone followed by pyrotinib + itraconazole, with a washout period in between.	Drug: pyrotinib tablet; single oral dose of SHR6390 or co-administered with itraconazole; Drug: Itraconazole capsule; 200 mg itraconazole QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of pyrotinib	Maximum concentration (Cmax) of pyrotinib	Day 1 and Day 9
AUC of pyrotinib	Area under the plasma concentration versus time curve of SHR6390	Day 1 and Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of pyrotinib	Time of maximum concentration of pyrotinib	Day 1 and Day 9
T1/2 of pyrotinib	Terminal half-life of pyrotinib	Day 1 and Day 9
AEs and SAEs	Adverse events and serious adverse events	From the first drug administration to 7 days after the last drug administration

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2019
• Primary Completion (Actual): October 11, 2019
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

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 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: HR-BLTN-DDI-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No