Placental Passage and Disposition of Drugs: A Physiology-based Approach

Pregnancy Clinical Trial

— PIANO  

Official title:

Placental Passage and Disposition of Drugs: A Physiology-based Approach

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02438631
• Other study ID #: PIANO
• Status: Recruiting
• Start date: February 2015
• Est. completion date: December 2028

Study information

• Verified date: September 2022
• Source: Radboud University Medical Center
• Contact: J van Drongelen
• Email: joris.vandrongelen[@]Radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators aim to integrate the outcomes in physiology-based pharmacokinetic (PBPK) models to put the generated data into context with medical conditions that require maternal or fetal drug therapy (e.g. HIV). These models will be validated with available 'real-life' maternal and fetal PK data, such as data from the PANNA network. PBPK models of drug therapy during pregnancy will provide a powerful tool to 1.) assist in designing rational dosing adjustments, 2.) prevent intervention-based research in pregnant women in the future, and 3.) guide future development of new molecular entities (e.g. preventing heavy investment in drugs with high predicted fetal exposure and potentially toxic effects in utero).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female
• Age > 18
• Signed informed consent
• >38 weeks pregnant

Exclusion Criteria:

• Retained placenta
• HIV infected
• Known hepatitis C infection
• Multiple pregnancy
• Congenital birth defects child
• Sectio EXIT procedure

Related Conditions & MeSH terms

• Pregnancy

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland

Sponsors (5)

Lead Sponsor	Collaborator
Radboud University Medical Center	Janssen Pharmaceuticals, Merck Sharp & Dohme LLC, PENTA Foundation, Top sector Life Sciences & Health

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	placental transfer	1.) An ex-vivo placenta perfusion model will be used to estimate placental passage of drugs	at delivery
Primary	histological profiling	Histological and protein profiling experiments will be conducted to investigate factors that may influence the placental passage and disposition of drugs (e.g. the abundance, localization and inter-individual variation of expression of enzymes and transporters).	at delivery
Primary	in vitro experiments	Furthermore, in vitro experiments will be conducted to estimate the pharmacodynamic effects of drugs on the placental barrier function itself (e.g. whether exposure to drugs can induce/reduce the expression of enzymes and transporters, as has been reported for several organs, such as the liver, intestine and kidney).	at delivery