"Drugs in Lactation" Analysis Consortium

Terminated

• Conditions: Lactation
• Interventions: Other: No intervention

• Registration Number: NCT02755194
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Some medications taken by the breastfeeding women are excreted into milk, posing a potential risk of toxicity to the infant. The first line of evidence required for toxicity risk assessment is prediction of drug levels in milk. However, pharmacokinetic (PK) information of drug excretion into milk is largely lacking, or limited to data from case reports. This makes it difficult to provide population-level prediction of drug levels in milk. The lack of data on this topic jeopardizes not only maternal adherence to drug therapy during breastfeeding but also establishment of breastfeeding, even if the drug is considered safe during nursing. Clearly, this clinical problem in drug safety is an important women's health issue, affecting both mother and infant. "Drugs in Lactation" Analysis Consortium (DLAC) is a "drug-in-milk" monitoring network, which is designed as a platform for efficient collection of patient milk samples in a real world setting to generate population predictions of drug excretion levels into human milk.

Detailed Description

OVERARCHING GOAL OF DLAC:

To establish a post-marketing "drug-in-milk" monitoring system for nursing women who are prescribed and using medications. Drugs in Lactation Analysis Consortium (DLAC) will provide risk assessment data and tools for toxicity detection in the form of population estimates and variations of drug levels in mother's milk and infant plasma for several common medications in a real world setting.

SPECIFIC OBJECTIVES:

* To generate data on drug levels in breast milk

* To develop a population pharmacokinetic model describing drug levels in milk

* To simulate/predict drug levels in milk in a population, based on the pop PK model

* To develop a physiologically-based pharmacokinetic (PBPK) model describing drug levels in infant serum

* To screen the breastfed infants of mothers on the study drugs for general health condition (medical issues, developmental milestones)

SCOPE AND RATIONALE:

Information on the extent of drug excretion into mother's milk is lacking, mainly due to the following two reasons: 1) nursing women are excluded from drug trials; 2) ethical and practical difficulties in conducting intensive-sampling PK studies in the breastfeeding mothers. Even if data exist, they are based on small numbers of patients, and it is difficult to translate the information into population estimates of drug levels in milk. DLAC is developed as a novel drug safety network using population PK (popPK) modeling approach, which allows population-level PK parameter estimation, modeling and simulation based on a scheme of sparse sampling per individual, systematically collected from a large number of nursing women on medication in real world setting. This approach will provide population risk estimates as probability distribution of reaching certain drug level in milk and plasma. Equipped with a versatile drug analysis core and a popPK modeling and simulation unit, DLAC will be able to generate PK estimates of a population in the context of breastfeeding.

Study Timeline

• Study Start: 2014-09
• Study First Submitted: 2016-04-21
• Study First Submitted QC: 2016-04-26
• Study First Posted: 2016-04-28
• Primary Completion: 2019-09-25
• Study Completion: 2019-09-25
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-19
• Last Update Posted: 2020-10-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 68

Inclusion Criteria

• Age over 18 years old Taking one or more drugs of interest of the study, at steady state

Exclusion Criteria

• Being unable to communicate in English, Colostrum phase (<1 week postpartum)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Breastfeeding women on the study medications	No intervention	The study population consists of lactating/breastfeeding women over the age of 18, who are able to communicate in English and are taking one or more of the study drugs (Infliximab, Adalimumab, Golimumab, Certolizumab, Etanercept, Methotrexate, Ezetimibe, Bupropion, Citalopram, Venlafaxine)

Primary Outcome Measures

Name	Time	Method
Drug levels in breast milk	Through the study completion, an average of 4 years	Robust parameter estimates from pop PK modelling usually require samples from \>30-50 individuals. Therefore, an average of 4 years is considered as the time frame, so that the required numbers of samples for each drug can be collected for population PK analysis and modelling.

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada