Identification and Validation of Biomarkers for Breast Cancer Resistance Protein (BCRP) (BCRPmarker)

Identification and Validation of Biomarkers for Breast Cancer Resistance Protein

This is an open-label, non-randomized, fixed-sequence study. Subjects will undergo a rosuvastatin phase and eltrombopag and rosuvastatin phase to identify biomarkers for Breast Cancer Resistance Protein (BCRP).

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Rosuvastatin (Inhibitor arm); Drug: Eltrombopag

Detailed Description

Membrane transporters are critical in the absorption, distribution and elimination of drugs, and are important target sites for drug-drug interactions (DDIs). During drug development, clinical studies characterizing transporter-mediated DDIs are frequently required. There has been enormous interest in identifying and validating serum biomarkers or surrogate probes to be used in predicting in vivo (clinical) DDIs. These biomarkers could complement in vitro studies, reducing false positive and false negative predictions, as well as the cost and time required for clinical development.

In this open-label, non-randomized, fixed-sequence study, subjects will undergo a rosuvastatin phase and eltrombopag and rosuvastatin phase to identify biomarkers for a membrane transporter known as Breast Cancer Resistance Protein (BCRP). The primary goal of this study is to validate and discover BCRP candidate biomarkers in a focused clinical DDI study with healthy volunteers to determine whether they can serve as clinical biomarkers for BCRP-mediated DDIs.

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

Contacts and Locations

• Study Contact: Name: Kathleen M Giacomini, Ph.D.; Phone Number: 41-5476-1936; Email: kathy.giacomini@ucsf.edu
• Study Contact Backup: Name: Sook Wah Yee, Ph.D.; Phone Number: 415-514-4363; Email: sookwah.yee@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Ucsf Ctsi Crc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy as judged by medical examination, medical history and normal biochemical and hematological measures.
• Normal urinalysis and renal function
• Male subjects weighing ≥ 50 kg and female subjects weighing ≥ 45 kg.
• Understand the nature and purpose of the study and provide informed consent.

Exclusion Criteria:

• Subjects who are pregnant, breastfeeding, or unwilling to practice non-hormonal forms of birth control during participation in the study.
• Self-reported drug allergies to rosuvastatin or eltrombopag
• Subjects that have smoked cigarettes, have smoked or ingested THC/marijuana or have used illegal substances (i.e., opiates, cocaine) in the past year.
• Subjects with any disease affecting or impairing the function of the liver, kidney or heart.
• Subjects with any blood or coagulation disorders.
• Subjects with diabetes mellitus, hyperthyroidism, hypothyroidism, cardiovascular disease, glaucoma.
• Subjects with gastrointestinal disease, gastrointestinal disorder, or gastrointestinal surgery.
• Subjects with known infection with HIV, Hepatitis B (HBsAg) or Hepatitis C (no laboratory diagnostics concerning these diseases will be performed within the present study).
• Subjects that are taking prescription (i.e., birth control pills), non-prescription and dietary supplements (i.e., turmeric, quercetin, kaempferol, Gingko biloba) within seven days of receiving the study dose in each phase of the study.
• Subjects with a condition, disease, or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Female subjects undergoing treatment for infertility or hormone replacement therapy.
• Subjects with abnormal laboratory results at screening as judged by the investigator or study physician.
• Participating in another research study while participating in this research study.
• Subjects that ingest grapefruit, grapefruit juice or grapefruit extract within seven days of receiving the study dose in each phase of the study.
• Non-English speaking.
• Subject has any signs or symptoms that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
• Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test (i.e., COVID19 RNA test) performed during the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo and Rosuvastatin; Subjects will be dosed with placebo tablet and Rosuvastatin 10mg tablet	Drug: Rosuvastatin; Rosuvastatin will be administered as follows: Day 1: single dose of 10 mg Rosuvastatin tablet.; Other Names: Crestor
Experimental: Eltrombopag and Rosuvastatin; Subjects will be dosed with Eltrombopag 75mg tablet and Rosuvastatin 10mg tablet	Drug: Rosuvastatin (Inhibitor arm); Rosuvastatin will be administered as follows: Day 8: single dose of 10 mg Rosuvastatin tablet.; Other Names: Cresto; Drug: Eltrombopag; Eltrombopag will be administered as follows: Day 8: single dose of 75 mg Eltrombopag tablet.; Other Names: Promacta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers.	Mean difference in area under the curve (AUC) between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg	24 and 72 hours
Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers.	Mean difference in Cmax between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg	24 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of BCRP biomarkers of co-administration of rosuvastatin and eltrombopag in healthy volunteers.	Mean difference in BCRP biomarker Cmax between rosuvastatin 10mg + placebo vs rosuvastatin 10mg + eltrombopag 75mg	24 and 72 hours

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Kathleen M Giacomini, Ph.D., University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: biomarker; eltrombopag; drug-drug interaction; rosuvastatin; membrane transporter
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 20-30638

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