- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06056583
Drug Excretion in Breast Milk
November 27, 2023 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
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
Interventional
Enrollment (Estimated)
50
Phase
- 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
- Name: Mary Hebert, PharmD, FCCP
- Phone Number: 206-616-5016
- Email: mhebert@uw.edu
Study Locations
-
-
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
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Study participants will include: healthy, lactating or pregnant and planning to breastfeed their infant, between 18-50 years of age, female and their nursing infant 3 weeks-8 months of age.
Exclusion Criteria:
• Age <18 or > 50 years old.
- Smokers
- Following multiple gestation (twins, triplets etc.)
- Allergy to cimetidine
- Pregnancy
Receiving medications that could lead to a drug interaction e.g.
- A: antacids, alprazolam, amphetamines, atazanavir, acalabrutinib, alosetron, amiodarone, amitriptyline, azelastine, amoxapine, alfuzosin,
- B: bisacodyl, bupropion, bosutinib,
- C: citalopram, chloroquine, codeine, clozapine, carmustine, clopidogrel, cyclosporine, carvedilol, cannabis, cefpodoxime, ceftibuten, clomipramine, cefditoren, chlordiazepoxide, chlorpromazine, cholecalciferol, cisapride, clonazepam, clorazepate, clomethiazole, carbamazepine,
- D: dofetilide, dihydrocodeine, duloxetine, delavirdine, dasatinib, domperidone, dothiepin, dilevalol, diltiazem, dutasteride, desipramine, doxepin, diazepam,
- E: escitalopram, epirubicin, eliglustat, estazolam, ethanol (on study day), ergocalciferol,
- F: fezolinetant, fluorouracil, finerenone, fexinidazole, flecainide, fluconazole, flurazepam, fosamprenavir, femoxetine,
- G: gefitinib, glipizide, glyburide, gliclazide, glimepiride,
- H: hydroxychloroquine, halazepam,
- I: infigratinib, imipramine, itraconazole,
- K: ketoconazole,
- L: ledipasvir, lornoxicam, labetalol, lidocaine, levoketoconazole, levomethadyl, lomitapide, loratadine,
- M: meperidine, morphine, mirtazapine, midazolam, metformin, metoclopramide, memantine, metronidazole, moclobemide,
- N: neratinib, nicotine, nebivolol, nisoldipine, nifedipine, nortriptyline, nimodipine, nicardipine, nilotinib, nitrazepam, nilvadipine, nitrendipine,
- O: oxycodone, octreotide, oxymorphone,
- P: posaconazole, piperaquine, pazopanib, pentoxifylline, paroxetine, phenytoin, pramipexole, propranolol, procainamide, phenindione, perfloxacin, praziquantel, protriptyline, prazepam, pontinib,
- Q: quinidine, quazepam, quinine,
- R: rilpivirine, roflumilast, risperidone, risedronate,
- S: succinylcholine, selpercatinib, sirolimus, secretin, sotorasib, sparsentan, sofobuvir, saquinavir, sertraline, sucralfate, sildenafil,
- T: terbinafine, tramadol, theophylline, tacrolimus, tizanidine, tolazoline, trimetrexate, tocainide, tamsulosin, timolol, tacrine, tolbutamide, trimipramine, tamoxifen, trimazosin, tinidazole, triazolam,
- V: vismodegib, verapamil, velpatasvir, venlafaxine, vardenafil,
- W: warfarin,
- Z: zalcitabine, zaleplon, zolmitriptan
- BCRP inhibitors: dasatinib, celecoxib, erlotinib, lopinavir, fostamatinib, docetaxel, barcitinib, imatinib, gefitnib, venetoclax, sunitinib, elacridar, Palbociclib, regorafenib, rucaparib, nilotinib, sorafenib, vemurafenib, afatinib, nelfinavir, paclitaxel, quercetin and alectinib
- BCRP inducers: venlafaxine, and dovitinib
- OCT inhibitors: trimethoprim, ranitidine, codeine, rocuronium, ganciclovir, acyclovir, dinoprostone, progesterone, prazosin, phenoxybenzamine, phenformin, procainamide, nicotine, choline, verapamil, quinine, pancuronium, disopyramide, desipramine, guanidine, probenecid, saquinavir, nelfinavir, chlorpheniramine, indinavir, reserpine, rucaparib, estradiol, pitolisant, choline, quinidine, amantadine, dexchlorpheniramine, doxazosin, efavirenz, nevirapine, clopidogrel, dacomitinib, gilteritinib, palbociclib, linagliptin, nintedanib, dronedarone, lasmiditan, formoterol, guanfacine, salmeterol, levofloxacin, osilodrostat, lurbinectedin, tirbanibulin cyproheptadine, infigratinib, atagepant, asciminib, abrocitinib, pacritinib, olaparib, tepotinib, tafenoquine, propranolol, oxprenolol, metoprolol, quinine, thiamine, norepinephrine, imipramine, grepafloxacine, amantadine, metformin, desipramine, famotidine, probenecid, cisplatin, quinacrine, amiloride, epinephrine, disopyramide, diphenhydramine, imatinib, flurazepam, bupropion, amiodarone, clopidogrel, cocaine, lamotrigine
- OCT inducers: none identified
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 |
Intervention / Treatment |
---|---|
Other: Healthy Lactating Women
Healthy Lactating Women will be studied on 3 study days and serve as their own control.
|
Cimetidine will serve as the probe drug
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
Collaborators
Investigators
- 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 (Estimated)
January 15, 2024
Primary Completion (Estimated)
September 30, 2028
Study Completion (Estimated)
September 30, 2028
Study Registration Dates
First Submitted
September 14, 2023
First Submitted That Met QC Criteria
September 20, 2023
First Posted (Actual)
September 28, 2023
Study Record Updates
Last Update Posted (Actual)
November 28, 2023
Last Update Submitted That Met QC Criteria
November 27, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Gastrointestinal Agents
- Cytochrome P-450 Enzyme Inhibitors
- Anti-Ulcer Agents
- Histamine Antagonists
- Histamine Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Histamine H2 Antagonists
- Cimetidine
Other Study ID 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.
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