Effect of Itraconazole on the Pharmacokinetics of Pyrotinib in Healthy Subjects

NCT04479891 | Completed Phase 1

• 1 other identifier: HR-BLTN-DDI-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Tmax of pyrotinib

  Day 1 and Day 9

• T1/2 of pyrotinib

  Day 1 and Day 9

• AEs and SAEs

  From the first drug administration to 7 days after the last drug administration

Study Arms (1)

pyrotinib alone, pyrotinib + itraconazole

EXPERIMENTAL

Sequential treatments of pyrotinib alone followed by pyrotinib + itraconazole, with a washout period in between.

Drug: pyrotinib tablet; Drug: Itraconazole capsule

Interventions

pyrotinib tablet DRUG

single oral dose of SHR6390 or co-administered with itraconazole

pyrotinib alone, pyrotinib + itraconazole

Itraconazole capsule DRUG

200 mg itraconazole QD

pyrotinib alone, pyrotinib + itraconazole

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

Location

MeSH Terms

Interventions

pyrotinib; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Pyrotinib alone and then combined with itraconazole

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 21, 2020
• Study Start: September 18, 2019
• Primary Completion: October 11, 2019
• Study Completion: November 30, 2019
• Last Updated: July 21, 2020

Record last verified: 2020-07

Locations

CN (1)