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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04542382
Recruitment Status : Not yet recruiting
First Posted : September 9, 2020
Last Update Posted : September 17, 2021
Sponsor:
Collaborator:
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Rosuvastatin Drug: Rosuvastatin (Inhibitor arm) Drug: Eltrombopag Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a single center, an open-label, non-randomized, fixed-sequence study.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Identification and Validation of Biomarkers for Breast Cancer Resistance Protein
Estimated Study Start Date : September 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Cresto

Drug: Eltrombopag

Eltrombopag will be administered as follows:

Day 8: single dose of 75 mg Eltrombopag tablet.

Other Name: Promacta




Primary Outcome Measures :
  1. Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers. [ Time Frame: 24 and 72 hours ]
    Mean difference in area under the curve (AUC) between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg

  2. Composite of pharmacokinetics of co-administration of rosuvastatin and eltrombopag in healthy volunteers. [ Time Frame: 24 hour ]
    Mean difference in Cmax between rosuvastatin 10mg + placebo versus rosuvastatin 10mg + eltrombopag 75mg


Secondary Outcome Measures :
  1. Composite of BCRP biomarkers of co-administration of rosuvastatin and eltrombopag in healthy volunteers. [ Time Frame: 24 and 72 hours ]
    Mean difference in BCRP biomarker Cmax between rosuvastatin 10mg + placebo vs rosuvastatin 10mg + eltrombopag 75mg



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04542382


Contacts
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Contact: Kathleen M Giacomini, Ph.D. 41-5476-1936 kathy.giacomini@ucsf.edu
Contact: Sook Wah Yee, Ph.D. 415-514-4363 sookwah.yee@ucsf.edu

Locations
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United States, California
Ucsf Ctsi Crc
San Francisco, California, United States, 94143
Contact: Deborah Zeitschel, RN, MSN, PhN    415-218-4927    crsprotocolservices@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
Food and Drug Administration (FDA)
Investigators
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Principal Investigator: Kathleen M Giacomini, Ph.D. University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04542382    
Other Study ID Numbers: 20-30638
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University of California, San Francisco:
membrane transporter
drug-drug interaction
rosuvastatin
eltrombopag
biomarker
Additional relevant MeSH terms:
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Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors