Breast Feeding Clinical Trial
— UmbrelLACTOfficial title:
Clinical Lactation Study on the Exposure to Medicines Via Human Milk: an Umbrella Study Protocol
NCT number | NCT06042803 |
Other study ID # | S67204 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | February 1, 2023 |
Est. completion date | May 2025 |
The goal of this observational study is to determine the concentration of medicines in human milk during maternal medicine intake. The main questions it aims to answer are: - What is the concentration of maternal medicines in human milk? - What is the (estimated) intake and exposure in the breastfed infant? Participants will be asked to - fill out a questionnaire regarding medical data of the mother and child - track medication intake for 3 days - collect milk samples during 24 hours - optionally, donate 2 blood samples of the mother and give consent to one blood sample of the child - fill out a questionnaire regarding the general health of the child.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | May 2025 |
Est. primary completion date | March 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - For breastfeeding women - Maternal age: = 18 year - Currently exclusively or partially breastfeeding (/expressing milk) at the time of milk sampling - Using medicines for any indication, with at least 5 half-lives of the medicine taken - Willing to express and collect human milk - Signed informed consent to participate and for processing their personal data - For infants - Gestational age at birth: =24 weeks - Parental signed informed consent to participate and for processing their personal data Exclusion Criteria: - Maternal age <18 years - Mother of twins - Not meeting the inclusion criteria |
Country | Name | City | State |
---|---|---|---|
Belgium | Universitaire Ziekenhuizen KU Leuven | Leuven | Vlaams-Brabant |
Lead Sponsor | Collaborator |
---|---|
Universitaire Ziekenhuizen KU Leuven | BELpREG, Innovative Medicines Initiative |
Belgium,
Anderson PO, Momper JD. Clinical lactation studies and the role of pharmacokinetic modeling and simulation in predicting drug exposures in breastfed infants. J Pharmacokinet Pharmacodyn. 2020 Aug;47(4):295-304. doi: 10.1007/s10928-020-09676-2. Epub 2020 Feb 7. — View Citation
Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016 Jul;100(1):42-52. doi: 10.1002/cpt.377. Epub 2016 May 13. — View Citation
Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z. — View Citation
Byrne JJ, Spong CY. "Is It Safe?" - The Many Unanswered Questions about Medications and Breast-Feeding. N Engl J Med. 2019 Apr 4;380(14):1296-1297. doi: 10.1056/NEJMp1817420. No abstract available. — View Citation
Del Ciampo LA, Del Ciampo IRL. Breastfeeding and the Benefits of Lactation for Women's Health. Rev Bras Ginecol Obstet. 2018 Jun;40(6):354-359. doi: 10.1055/s-0038-1657766. Epub 2018 Jul 6. — View Citation
Garessus EDG, Mielke H, Gundert-Remy U. Exposure of Infants to Isoniazid via Breast Milk After Maternal Drug Intake of Recommended Doses Is Clinically Insignificant Irrespective of Metaboliser Status. A Physiologically-Based Pharmacokinetic (PBPK) Modelling Approach to Estimate Drug Exposure of Infants via Breast-Feeding. Front Pharmacol. 2019 Jan 22;10:5. doi: 10.3389/fphar.2019.00005. eCollection 2019. — View Citation
Jones HM, Mayawala K, Poulin P. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches. AAPS J. 2013 Apr;15(2):377-87. doi: 10.1208/s12248-012-9446-2. Epub 2012 Dec 27. — View Citation
Kimura S, Morimoto K, Okamoto H, Ueda H, Kobayashi D, Kobayashi J, Morimoto Y. Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk. Arch Pharm Res. 2006 May;29(5):424-9. doi: 10.1007/BF02968594. — View Citation
Koshimichi H, Ito K, Hisaka A, Honma M, Suzuki H. Analysis and prediction of drug transfer into human milk taking into consideration secretion and reuptake clearances across the mammary epithelia. Drug Metab Dispos. 2011 Dec;39(12):2370-80. doi: 10.1124/dmd.111.040972. Epub 2011 Sep 22. — View Citation
Maharaj AR, Edginton AN. Physiologically based pharmacokinetic modeling and simulation in pediatric drug development. CPT Pharmacometrics Syst Pharmacol. 2014 Oct 22;3(11):e150. doi: 10.1038/psp.2014.45. — View Citation
McNamara PJ, Burgio D, Yoo SD. Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk. J Pharmacol Exp Ther. 1992 Jun;261(3):918-23. — View Citation
Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol. 2013 Apr 17;2(4):e38. doi: 10.1038/psp.2013.14. No abstract available. — View Citation
Nauwelaerts N, Ceulemans M, Deferm N, Eerdekens A, Lammens B, Armoudjian Y, Van Calsteren K, Allegaert K, de Vries L, Annaert P, Smits A. Case Report: Bosentan and Sildenafil Exposure in Human Milk - A Contribution From the ConcePTION Project. Front Pharmacol. 2022 Jun 15;13:881084. doi: 10.3389/fphar.2022.881084. eCollection 2022. — View Citation
Nauwelaerts N, Deferm N, Smits A, Bernardini C, Lammens B, Gandia P, Panchaud A, Nordeng H, Bacci ML, Forni M, Ventrella D, Van Calsteren K, DeLise A, Huys I, Bouisset-Leonard M, Allegaert K, Annaert P. A comprehensive review on non-clinical methods to study transfer of medication into breast milk - A contribution from the ConcePTION project. Biomed Pharmacother. 2021 Apr;136:111038. doi: 10.1016/j.biopha.2020.111038. Epub 2021 Jan 30. — View Citation
Saha MR, Ryan K, Amir LH. Postpartum women's use of medicines and breastfeeding practices: a systematic review. Int Breastfeed J. 2015 Oct 28;10:28. doi: 10.1186/s13006-015-0053-6. eCollection 2015. — View Citation
* Note: There are 15 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The concentration of maternal medicines in human milk | Quantification of the concentration of medicines in human milk: concentration, milk-to-plasma (M/P) ratio;
The PK parameters of medicines and relevant metabolites in human milk: area under the milk concentration-time curve (AUC), the average concentration (AUC divided by dosing interval), peak and trough milk concentrations (if available, depending on dosing regimen and lactation regimen), and time to reach peak milk concentration. The PK parameters of medicines and relevant metabolites in plasma from lactating women compared to available scientific literature results, such as AUC, peak plasma concentration, time to peak plasma concentration, plasma clearance or apparent oral clearance, apparent volume of distribution and terminal half-life. |
24 hours (sampling day) | |
Secondary | The estimated intake of medicines in the nursing infant via human milk: DID | The daily infant dosage (DID)(mg/d)
= ?(total drug concentration in each milk collection x expressed milk volume in each milk collection) |
24 hours (sampling day) | |
Secondary | The estimated intake of medicines in the nursing infant via human milk: eDID - maxDID | The estimated Daily infant dosage (eDID)(mg/kg/d) and the infant risk (maxDID) expressed as a daily weight normalized dose (mg/kg/d), with 150mL/kg/d and 200mL/kg/d as maximum estimated milk intake, respectively. The calculation of the M/P ratio is based on the AUC on multiple time points, if possible.
= M/P ratio x average plasma concentration x estimated milk intake |
24 hours (sampling day) | |
Secondary | The estimated intake of medicines in the nursing infant via human milk: RID | The relative infant dose (RID)(%)
= [eDID (mg/kg/d)/Maternal Dosage (mg/kg/d)] x 100 |
24 hours (sampling day) | |
Secondary | The estimated intake of medicines in the nursing infant via human milk: RIDtherapeutic | The relative infant therapeutic dose (RIDtherapeutic)(%)
= [estimated daily infant dosage (mg/kg/d)/Daily therapeutic infant dosage (mg/kg/d)] x 100 |
24 hours (sampling day) | |
Secondary | The estimated intake of medicines in the nursing infant via human milk: Css, ave | The average infant medicine concentration at steady state (Css, ave)(ng/mL), if oral bioavailability (F) and drug clearance (CL) are known for the paediatric population
= oral bioavailability (F) x [eDID (mg/kg/d)/Clearance (CL; L/d)]x1000 |
24 hours (sampling day) | |
Secondary | The systemic exposure to medicines in the nursing infant via breastfeeding: infant systemic medicine concentration | The measured infant systemic medicine concentration if the parents give consent for collection of a blood sample from the infant; | 24 hours (sampling day) | |
Secondary | The systemic exposure to medicines in the nursing infant via breastfeeding: infant/maternal plasma ratio | The infant/maternal plasma ratio if a blood sample from the infant is available; | 24 hours (sampling day) | |
Secondary | The systemic exposure to medicines in the nursing infant via breastfeeding | Rate of medicine absorption in infants through human milk (e.g., infant plasma concentration/milk concentration) if a blood sample from the infant is available; | 24 hours (sampling day) | |
Secondary | The general health status (including possible adverse effects) of the nursing infant | The general health status of the infant, reported by maternal questionnaire. | 2 weeks (in case of an acute maternal treatment/condition) or 2 months (in case of an chronic maternal treatment/condition) | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: Concentration-time profile | Evaluation of the predictive performance of PBPK models by assessing whether the observed concentration-time profiles were within the 5th-95th percentile of the population prediction of the PBPK models. | 24 hours | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: M/P ratio | Evaluation of the predictive performance of PBPK models by assessing whether the observed Milk-to-plasma ratio were within the 5th-95th percentile of the population prediction of the PBPK models. | 24 hours | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: Cmax | Evaluation of the predictive performance of PBPK models by assessing whether the observed maximum concentration (Cmax) were within the 5th-95th percentile of the population prediction of the PBPK models. | 24 hours | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: AUC | Evaluation of the predictive performance of PBPK models by assessing whether the observed Area-under-the-curve (AUC) were within the 5th-95th percentile of the population prediction of the PBPK models. | 24 hours | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: DID | Evaluation of the predictive performance of PBPK models by comparing the predicted daily infant dosage (DID) with the calculated DID [The daily infant dosage (DID)(mg/d) = ?(total drug concentration in each milk collection x expressed milk volume in each milk collection), calculated from the concentrations found in the human milk samples]. | 24 hours | |
Secondary | Evaluation of physiologically-based pharmacokinetic (PBPK) models: RID | Evaluation of the predictive performance of PBPK models by comparing the predicted relative infant dose (RID) with the calculated RID [The relative infant dose (RID)(%) = [eDID (mg/kg/d)/Maternal Dosage (mg/kg/d)] x 100]. | 24 hours |
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