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

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).

Study Overview

• Status: Recruiting
• Conditions: Pregnancy

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: J van Drongelen; Email: joris.vandrongelen@Radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Recruiting
      • Radboud University Medical Centre
      • Contact: Joris M van Drongelen, MD PhD; Email: joris.vandrongelen@Radboudumc.nl
      • Principal Investigator: Joris van Drongelen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
placental transfer	1.) An ex-vivo placenta perfusion model will be used to estimate placental passage of drugs	at delivery
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
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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Merck Sharp & Dohme LLC; Janssen Pharmaceuticals; PENTA Foundation; Top sector Life Sciences & Health
• Investigators: Principal Investigator: J van Drongelen, Radboud university medical center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Anticipated): December 1, 2028
• Study Completion (Anticipated): December 1, 2028

Study Registration Dates

• First Submitted: May 6, 2015
• First Submitted That Met QC Criteria: May 7, 2015
• First Posted (Estimate): May 8, 2015

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: placenta; placental passage
• Other Study ID Numbers: PIANO