Drug-Drug Interaction of Pyrotinib With a Moderate CYP3A Inducer

NCT04680091 | Unknown Phase 1

• 1 other identifier: HR-BLTN-DDI-05
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects, Drug-drug Interaction, Pyrotinib

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (2)

Efavirenz 600 mg + Pyrotinib 400 mg

EXPERIMENTAL

Drug: Pyrotinib Maleate; Drug: Efavirenz

Pyrotinib 400 mg

ACTIVE COMPARATOR

Drug: Pyrotinib Maleate

Interventions

Pyrotinib Maleate DRUG

single oral dose, 400 mg, fed.

Efavirenz 600 mg + Pyrotinib 400 mg; Pyrotinib 400 mg

Efavirenz DRUG

single oral dose, 600 mg, fasted, at bedtime.

Efavirenz 600 mg + Pyrotinib 400 mg

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;
• 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,

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Jiangsu HengRui Medicine Co., Ltd.

Shanghai, Shanghai Municipality, 201203, China

Location

MeSH Terms

Interventions

efavirenz

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To observe the effect of efavirenz on the pharmacokinetics of pyrotinib and to evaluate the safety of pyrotinib, efavirenz and their coadministration in Chinese healthy subjects. The subjects will take pyrotinib at first single dose, then washout period, and take it at second single dose after multiple administration of efavirenz to get a full induction condition.

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: December 22, 2020
• Study Start: November 12, 2020
• Primary Completion: January 28, 2021
• Study Completion: December 30, 2021
• Last Updated: April 22, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)