Drug Excretion in Breast Milk

August 2, 2024 updated by: Mary Hebert, University of Washington

Postpartum Activity and Expression of BCRP and OCT1 Drug Transporters in the Mammary Gland

This is a prospective, non-randomized, phase I study design evaluating the in vivo activities and expression of OCT1 and BCRP in mammary gland of lactating women at three time points postpartum.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Each woman will receive a single oral dose of cimetidine 200 mg on each of 3 study days (3-5 weeks, 3-4 months, and 6-8 months postpartum) followed by serial collection of blood, urine and breast milk samples over 12-hours. Cimetidine concentrations will be assay using a validated LC/MS/MS assay. Subjects will be genotyped for OCT1 and BCRP. Mammary epithelial cells will be isolated from breast milk and transporter expression will be quantified. Each woman will serve as her own control.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Mary Hebert, PharmD, FCCP
  • Phone Number: 206-616-5016
  • Email: mhebert@uw.edu

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
          • Mary F Hebert, PharmD
          • Phone Number: 206-616-5016
          • Email: mhebert@uw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria

  1. Healthy postpartum women
  2. 18-50 years of age and their infants
  3. Able to provide written informed consent

Exclusion criteria

  1. Receiving cimetidine within the 3 days prior to each study day. Concomitant administration of cimetidine will confound interpretation of study results.
  2. Hypersensitivity to cimetidine Patients with known allergic reactions to cimetidine will be excluded for safety reasons
  3. Receiving medication known to interact with cimetidine: OCT, BCRP, CYP3A4, CYP2D6, CYP1A2 and CYP2C9 substrates (e.g. amiodarone, clopidogrel, diazepam, ketoconazole, metformin, nifedipine, phenytoin, procainamide, theophylline,tricyclic antidepressants and warfarin) Patients with drug interactions will be excluded for safety reasons.
  4. Receiving BCRP inhibitors/inducers (afatinib, aripipraxole, axitinib, cimetidine, cyclosporine, curcumin/tumeric, delavirdine, efavirenz, elacridar, elvitegravir, etravirine, FTC, 5-fluorouracil, fluvastatin, imatinib, lanzoprazole, lapatinib, lopinavir, maraviroc, nelfinavir, nebicapone, nilotinib, novobiocin, oltipraz, omeprazole, pantoprazole, phenobarbital, promazine, rabeprazole, riboflavin, rifampicin, risperidone, saquinavir, sirolimus, sorafenib, sulfasalazine, sunitinib, tacrolimus, tariquidar, telaprevir, telatinib, teriflunomide, tolcapone, triflunomide, trametinib, trifluoperazine, venlafaxine, zidonuvir), OCT1 inhibitors/inducers (acyclovir, amantadine, amiloride, amitriptyline, bucindolol, carvedilol, chlorpheniramine, chlorpromazine, cimetidine, citalopram, clonidine, clopidogrel, clotrimazole, clozapine, cocaine, corticosterone, cyclosporine, daclatasvir, darunavir, desipramine, dextromethorphan, diltiazem, disopyramide, dronedarone, efavirenz, famotidine, fentanyl, fluvoxamine, formoterol, fuloxetine, griseofulvin, doxazosine, ganciclovir, guanfacine, imipramine, indinavir, isavuconazole, itraconazole, ketoconazole, lamotrigine, lasmiditan, levofloxacin, levomepromazine, lidocaine, maprotiline, methylnicotinamide, morphine, moxifloxacin, nefazodone, nelfinavir, nevirapine, nicotine, nomifensine, ondansetron, oxybutynin, paroxetine, pentamidine, phenoxybenzamine, prazosin, probenecid, procainamide, propafenone, pyrazinamide, quetiapine,quinidine, quinine, reboxetine, remoxidpride, reseripine, rifampicin, ritonavir, salmeterol, saquinavir, tramadol, trimethoprim, trimipramine, verapamil) Inhibitors and inducers of the drug transporters will confound data analysis and interpretation.
  5. Kidney disease could confound data analysis and interpretation. Therefore, patients with known kidney disease with documented renal function impairment will be excluded from the study. Current serum creatinine > 1.2 mg/dL in their medical record will be excluded.
  6. Known liver disease Liver disease will confound data analysis and interpretation. Therefore, patients with known significant liver disease will be excluded from the study. Current ALT exceeding 2-times the upper limit of normal in their medical record will be excluded.
  7. Inability to fast for 4 hours prior to the study. To limit PK variability across study days, subjects will be requested to fast for 4 hours prior to each study day.
  8. Smokers (tobacco or other nicotine containing products Nicotine interacts with OCT1 and will confound data analysis and interpretation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Healthy Lactating Women
Healthy Lactating Women will be studied on 3 study days and serve as their own control.
Drug: Cimetidine 200 MG
Cimetidine will serve as the probe drug
Other Names:
  • Tagamet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mammary clearance of cimetidine
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Cimetidine excretion into breast milk at three postpartum stages
3-5 weeks, 3-4 months and 6-8 months postpartum
Mammary epithelial cell expression of BCRP
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
BCRP protein expression in MECs at three postpartum stages
3-5 weeks, 3-4 months and 6-8 months postpartum
Mammary epithelial cell expression of OCT1
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
OCT1 protein expression in MECs at three postpartum stages
3-5 weeks, 3-4 months and 6-8 months postpartum

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cimetidine relative infant dose and infant concentration
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
cimetidine relative infant dose (RID) and infant concentration
3-5 weeks, 3-4 months and 6-8 months postpartum
Relationship between OCT1 expression and activity
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effect of time postpartum on OCT1 protein expression in MECs and correlation with cimetidine mammary CL
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine CL/F
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine renal CL
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine renal secretion CL
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine mammary CL
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine AUC
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine Cmax
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine Tmax
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine half-life
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine apparent oral volume of distribution
3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effects of time postpartum on cimetidine elimination rate constant
3-5 weeks, 3-4 months and 6-8 months postpartum
Relationship between BCRP expression and activity
Time Frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Effect of time postpartum on BCRP protein expression in MECs and correlation with cimetidine mammary CL
3-5 weeks, 3-4 months and 6-8 months postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Washington

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mary Hebert, PharmD, FCCP, University of Washington

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 4, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00018397
  • R01HD112282 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We are committed to share data with the academic community and researcher-at-large. We will adhere to the NIH Grant Policy on Sharing Research Data and Resources. That is, after final data collection and analysis and after full peer review is performed on our data, the de-identified data generated by this project will be made available when requested by the academic community and researchers-at-large contingent upon Material Transfer Agreements with the University of Washington.

IPD Sharing Time Frame

After peer review and publication of data.

IPD Sharing Access Criteria

We are committed to share data with the academic community and researcher-at-large. We will adhere to the NIH Grant Policy on Sharing Research Data and Resources. That is, after final data collection and analysis and after full peer review is performed on our data, the de-identified data generated by this project will be made available when requested by the academic community and researchers-at-large contingent upon Material Transfer Agreements with the University of Washington.

IPD Sharing Supporting Information Type

  • CSR

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings