Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding

Recruiting

• Conditions: Epilepsy; Pregnancy Related
• Interventions: Drug: Lamotrigine; Drug: Levetiracetam; Drug: Oxcarbazepine

• Registration Number: NCT05450978
• Lead Sponsor: University of Pittsburgh

Brief Summary

This project focuses on anti-seizure medication (ASM) clearance and physiological factors determining blood concentrations in pregnant adult women with epilepsy and amounts of exposure to their unborn children and nursing infants.

Detailed Description

The goal of this study is to develop modeling of pharmacokinetic changes for Antiseizure medications (ASMs), lamotrigine (LTG), and levetiracetam (LEV) during pregnancy and postpartum that can be used to:

1. Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring.

2. Predict exposure of ASMs in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity.

Hypotheses:

1. Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.

2. Validated model allows the prediction of drug concentration changes at all stages throughout and after pregnancy, which will more accurately predict increased seizures and medication side effects.

Additionally, pilot data will be obtained for oxcarbazepine (OXC) in a small number of participants and contribute to data for ASMs that undergo glucuronidation (LTG).

Study Timeline

• Study First Submitted: 2022-06-22
• Study First Submitted QC: 2022-07-06
• Study First Posted: 2022-07-11
• Study Start: 2022-07-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-18
• Primary Completion: 2027-04-01
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

• Woman with epilepsy between the ages of 18-45 planning pregnancy or in the early first trimester of pregnancy.
• Women with epilepsy ability to maintain a daily medical diary
• Women with epilepsy ability to answer side effect questionnaires
• Women with epilepsy currently being treated with lamotrigine (LTG) or levetiracetam (LEV) or oxcarbazepine (OXC)

Exclusion Criteria

• Women with epilepsy having history of functional seizures.
• Women with epilepsy history of other major medical illnesses including renal or hepatic disease, progressive cerebral disease,
• Women with epilepsy who have inability to maintain a seizure and medication daily diary
• Women with epilepsy with present or recent history of drug or alcohol abuse, or the use of any concomitant medications that interact with the ASM they are taking (lamotrigine, levetiracetam, oxcarbazepine).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Lamotrigine (LTG)	Lamotrigine	Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG)
Levetiracetam (LEV)	Levetiracetam	Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV)
Oxcarbazepine (OXC)	Oxcarbazepine	Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC)

Primary Outcome Measures

Name	Time	Method
Anti-Seizure Medication (ASM) Clearance	Through study completion, an average of 18 months.	ASM Clearance will be calculated from measurements of lamotrigine, oxcarbazepine, and levetiracetam blood concentrations, serum creatinine and 24-hour urine collection (for levetiracetam), glucuronidated metabolite (for lamotrigine), steroid hormones, medication formulation and doses, time since recent doses, and participant weight.

Secondary Outcome Measures

Name	Time	Method
Seizure Frequency	Through study completion, an average of 18 months.	Participants will keep a daily seizure diary throughout their participation in the study. The diary will be reviewed at each study visit.
Anti-seizure Medication (ASM) Side Effects	Through study completion, an average of 18 months	An ASM Side Effect Questionnaire will be administered and a neurologic examination will be performed at each study visit.
Placental passage of Anti-Seizure Medications (ASM)	Through study completion, an average of 18 months	Maternal blood will be drawn and umbilical cord blood will be collected, for measurements of ASM concentrations for lamotrigine, oxcarbazepine, and levetiracetam.

Trial Locations

Locations (1)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States