Effect of Montmorillonite Power or Loperamide on the Pharmacokinetics of Pyrotinib in Healthy Subjects

NCT05252546 | Completed Phase 1

• 1 other identifier: HR-BLTN-DDI-07
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the effect of anti-diarrhea drug Montmorillonite Power or Loperamide on the single dose pharmacokinetic parameters of pyrotinib in healthy Chinese subjects. The safety of pyrotinib alone and when co-administered with each drug will also be assessed.

Conditions

HER2-positive Recurrent / Metastatic Breast Cancer

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 pyrotinib

  Day 1 and Day 9

Secondary Outcomes (4)

• PK parameters （Tmax） of pyrotinib

  Day 1 and Day 9

• AEs and SAEs

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

• PK parameters （CL/F） of pyrotinib

  Day 1 and Day 9

• PK parameters （Vz/F） of pyrotinib

  Day 1 and Day 9

Study Arms (1)

pyrotinib alone, then pyrotinib + Montmorillonite Power or Loperamide

EXPERIMENTAL

Sequential treatments of pyrotinib alone followed by pyrotinib + Montmorillonite Power or Loperamide, with a washout period in between.

Drug: pyrotinib tablet; Drug: Montmorillonite Power; Drug: Loperamide

Interventions

pyrotinib tablet DRUG

single oral dose of pyrotinib or co-administered with Montmorillonite Power or Loperamide

pyrotinib alone, then pyrotinib + Montmorillonite Power or Loperamide

Montmorillonite Power DRUG

3 g or one pouch of montmorillonite power 2 hours after pyrotinib administration

pyrotinib alone, then pyrotinib + Montmorillonite Power or Loperamide

Loperamide DRUG

4 mg of loperamide with pyrotinib followed by 2mg every 2 hours for 2 times for a total of 8mg/day

pyrotinib alone, then pyrotinib + Montmorillonite Power or Loperamide

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.
• Healthy male and female subjects aged 18 to 45 years on the day of signing the informed consent form; appropriate proportion of subjects of different genders (no less than 3 of single gender) required in both groups A and B.
• Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19 \~ 26 kg/m2.
• Subjects of childbearing potential and their partners have no birth plan and voluntarily take effective contraception during the course of clinical trial until 3 months after the last dose (Female subjects are also required to use highly effective non-drug contraception starting two weeks before study entry and can use contraceptives after study completion).

You may not qualify if:

• Blood donation no less than 400 mL or have blood transfusion within 3 months of dosing.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound or known allergy to pyrotinib, montmorillonite power, loperamide or the excipients;
• History of drug abuse in the past 5 years, or positive for drug abuse screening;
• History of alcoholism with alcohol consumption over 14 units per week; heavy smoker; and can't abstain from smoking and alcohol during the study
• QTcF \>470 msec for females or \>450 msec for males by 12 lead electrocardiograph;
• Left ventricular ejection fraction (LVEF) \<50% by echocardiography
• Significant history or clinical manifestation of any neurological, cardiovascular, renal, gastrointestinal, pulmonary, respiratory, metabolic and musculoskeletal disorder, as determined by the Investigator (or designee).
• Any surgery within 6 months before screening;
• Intake of hepatotoxic drugs for a long time within 6 months before screening;
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months;
• Subjects who took any drugs that change liver enzymes activity within 28 days before dosing;
• Subjects who took any prescription drugs, over-the-counter drugs or vitamins, health products or herbal medicine within 14 days before dosing;
• Clinically significant abnormalities as determined by the Investigator (or designee) in general physical examination, vital signs, laboratory tests, etc.
• Pregnant or lactating females
• Positive serology test results for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody or human immunodeficiency virus antibody.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Related Publications (1)

• Wang Y, Li D, Zhang T, Xu S, Zhang Y, Zhao K, Li S, Shen K, Li X, Xu P. Evaluation of the pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib in healthy volunteers. Front Pharmacol. 2025 May 12;16:1563556. doi: 10.3389/fphar.2025.1563556. eCollection 2025.

  PMID: 40433999 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Loperamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Model Details: Pyrotinib alone and then combined with Montmorillonite Power or Loperamide

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: February 23, 2022
• Study Start: March 8, 2022
• Primary Completion: August 2, 2022
• Study Completion: August 2, 2022
• Last Updated: December 23, 2022

Record last verified: 2022-12

Locations

CN (1)