Clinical trial NCT02755194: "Drugs in Lactation" Analysis Consortium
Official title: "Drugs in Lactation" Analysis Consortium (DLAC)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Lactation
Keywords: pharmacokinetics
Drug-in-milk
breastfeeding
drug safety
population pharmacokinetics
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Lactating women over the age of 18 who are taking one of the drugs of interest of the study

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Drug levels in breast milk
timeFrame: Through the study completion, an average of 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Shinya Ito, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: