Drug-Drug Interaction of Pyrotinib With a Moderate CYP3A Inducer

A Single-Center, Single-Arm, Open-Label, Fixed-Sequence Phase I Drug-Drug Interaction Clinical Study of the Effect of Efavirenz on Pharmacokinetics of Maleate Pyrotinib in Chinese Healthy Subjects.

This drug-drug interaction (DDI) study had been designed to investigate the effect of a moderate CYP 3A inducer efavirenz on the pharmacokinetics of maleate pyrotinib in Chinese healthy volunteers.

Study Overview

• Status: Unknown
• Conditions: Healthy Subjects, Drug-drug Interaction, Pyrotinib
• Intervention / Treatment: Drug: Pyrotinib Maleate; Drug: Efavirenz

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201203
      • Jiangsu HengRui Medicine Co., Ltd.

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;
• Ability to complete the study as required by the protocol;
• Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
• Body weight ≥ 50 kg for male and female, and body mass index (BMI) within the range of 19 ~ 26 kg /m2 (including 19 and 26);
• In females, documented surgical sterilization, postmenopausal status for at least 1 year (follicle stimulating hormone [FSH] > 40 mIU/mL serum at Screening), or agreement to use an approved form of contraception
• In males, agreement to avoid sperm donation for 6 months days after the dose of pyrotinib
• Liver function test results must be below the upper limit of normal.
• Participants must agree to refrain from donation of whole blood and other blood products from 90 days prior to Screening,

Exclusion Criteria:

• Loss of more than 400 mL blood during the 3 months before the trial (eg, as a blood donor)
• Allergic constitution;
• History of drug use, or drug abuse screening positive;
• Alcoholic or often drinkers;
• A smoker with 5 cigarettes per day for more than 90 days;
• Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy participants), anti-treponema pallidum virus (TP), or antihuman immunodeficiency virus (HIV) Type 1 and Type 2 (all subjects)
• Use of any drugs or substances known to be inhibitors or inducers of CYP3A4/5 within 90 days from the first dose or 5 half-lives, if known, of the drugs or substances, whichever is greater, prior to pyrotinib administration and during the study.
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efavirenz 600 mg + Pyrotinib 400 mg	Drug: Pyrotinib Maleate; single oral dose, 400 mg, fed.; Drug: Efavirenz; single oral dose, 600 mg, fasted, at bedtime.
Active Comparator: Pyrotinib 400 mg	Drug: Pyrotinib Maleate; single oral dose, 400 mg, fed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Summary of Pharmacokinetic parameters Maximum Plasma Concentration (Cmax) for pyrotinib.	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
Summary of Pharmacokinetic parameters Area Under the Plasma Concentration-time Curve from 0 to any time before the last quantifiable concentration (AUC0-t) for pyrotinib.	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
Summary of Pharmacokinetic parameters Area Under the Plasma Concentration-time Curve from 0 to infinite time (AUCinf) for pyrotinib.	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics parameters (Tmax) of pyrotinib;	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
Pharmacokinetics parameters (T1/2) of pyrotinib;	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
Pharmacokinetics parameters (CL) of pyrotinib;	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
Pharmacokinetics parameters (Vd) of pyrotinib;	predose, 1, 2, 3, 4, 4.5, 5, 5.5, 7, 9, 12, 24, 48, 72, 96 h for Day1 and predose, 0.5, 1, 1.75, 2.5, 3.25, 4, 4.75, 5.5, 6.5, 8, 12, 24, 48, 72 h for Day20
The incidence and severity of adverse events/serious adverse events (based on NCI-CTCAE 5.0): Laboratory indicators, 12-lead electrocardiogram (ECG), physical examination, vital signs, etc.	Baseline up to 14 days post last dose, up to approximately 2 month

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): January 28, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz
• Other Study ID Numbers: HR-BLTN-DDI-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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