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

Epilepsy Clinical Trial

— PBPK  

Official title:

Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05450978
• Other study ID #: STUDY21090138
• Secondary ID: R01HD105305
• Status: Recruiting
• Start date: July 20, 2022
• Est. completion date: May 21, 2026

Study information

• Verified date: January 2024
• Source: University of Pittsburgh
• Contact: Nikhil Khongbantabam, BS
• Phone: 4125924018
• Email: nik66[@]pitt.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 LTG and LEV 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 (WWE). 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 21, 2026
• Est. primary completion date: May 21, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 45 Years

Eligibility

Inclusion Criteria:

• Women planning pregnancy within the next 6 months.
• Women currently being treated with lamotrigine (LTG) or levetiracetam (LEV) for a diagnosis of epilepsy

Exclusion Criteria:

• History of psychogenic non-epileptic spells
• History of other major medical illnesses including renal or hepatic disease, progressive cerebral disease,
• Inability to maintain a seizure and medication daily diary
• 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 or levetiracetam).

Related Conditions & MeSH terms

• Epilepsy
• Pregnancy Related

Intervention

Drug:
• Lamotrigine
Anti-seizure concentrations
• Levetiracetam
Anti-seizure concentrations

Locations

Country	Name	City	State
United States	Kaufmann Medical Building	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Page B. Pennell, MD	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Birnbaum AK, Meador KJ, Karanam A, Brown C, May RC, Gerard EE, Gedzelman ER, Penovich PE, Kalayjian LA, Cavitt J, Pack AM, Miller JW, Stowe ZN, Pennell PB; MONEAD Investigator Group. Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy. JAMA Neurol. 2020 Apr 1;77(4):441-450. doi: 10.1001/jamaneurol.2019.4443. — View Citation

Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, Gedzelman E, Cavitt J, Hwang S, Pack AM, Sam M, Miller JW, Wilson SH, Brown C, Birnbaum AK, Meador KJ; MONEAD Study Group. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556. doi: 10.1056/NEJMoa2008663. — View Citation

Pennell PB, Karanam A, Meador KJ, Gerard E, Kalayjian L, Penovich P, Matthews A, McElrath TM, Birnbaum AK; MONEAD Study Group. Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study. JAMA Neurol. 2022 Apr 1;79(4):370-379. doi: 10.1001/jamaneurol.2021.5487. — View Citation

Outcome

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