Epilepsy in PregnancyEPICEINTENCT04117425
Pharmacokinetic and Placental Transfer of Levetiracetam
A study testing biological collection in people with Epilepsy in Pregnancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Hypotheses: The treatment of epilepsy during pregnancy is difficult because of the risk of anti-epileptic drugs on the one hand and the risk of destabilization of epilepsy in the mother on the other hand. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Epilepsy in Pregnancy
- What is being tested?
- biological collection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- 20 Apr 2022to 16 Aug 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- pregnant Women of childbearing age who are pregnant
- Age ≥18 years
- Women with epilepsy treated with levetiracetam in monotherapy or combination
- affiliated to a social security scheme (or entitled)
Who cannot join
- Women treated with antiepileptics for pathology other than epilepsy
- Women treated with a combination of more than 3 antiepileptics
- Severe anemia
- Renal failure (moderate to severe)
- Hepatic impairment (moderate to severe)
- Alcohol and/or recreational drug use
Show all 10Show fewer
- Trend towards non-compliance with treatment
- Inability to maintain a Crisis Observation Workbook
- Suicidal Ideas
- Uncontrolled thyroid disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Maternal Pharmacokinetic and Placental Transfer of Levetiracetam
Hypotheses: The treatment of epilepsy during pregnancy is difficult because of the risk of anti-epileptic drugs on the one hand and the risk of destabilization of epilepsy in the mother on the other hand. There is limited data on the pharmacokinetics (concentration study) and pharmacodynamics (efficacy and toxicity effects study) of levetiracetam in pregnant women. The few studies focus on few women and show very strong interindividual variability and a tendency to decrease total concentrations.
Main objective: To develop a population pharmacokinetic model of levetiracetam during pregnancy. After the study, this model could be used to propose dose adjustments to maintain stable concentrations in pregnant women throughout pregnancy.
Read more
Secondary objectives:
- Describe placental transfer during childbirth and during a medical termination of pregnancy
- Link the concentration and its variation in the individual to the effects of treatment
Read the detailed description
Methodology: Are included by the neurology service, pregnant women which are already under levetiracetam and / or obstetric gynecology services for her treatment of epilepsy, pregnant women at first consultation. Women are already taking levetiracetam and the drug is not provided by the study40 mother-child couples, as well as 10 women who undergo a medical termination of pregnancy will have to be included in the study, in 7 maternities in Paris.
Women are already taking the drugs, according to the practices of the different services, and the study will not change their prescriptions of these drugs. The women will have a blood sample at 3 visits during pregnancy (11-14 weeks, 24-28 weeks and 35-39 weeks) and at the post-partum consultation. At delivery, a collection of the mother, cord blood and amniotic fluid will be performed. A salivary specimen will be routinely collected at the same time as the mother's plasma sample.
The pharmaco-statistical analysis will be conducted using non-linear mixed-effect modeling programs (Monolix and Nonmem) to calculate the main pharmacokinetic parameters of the mother and fetus and to estimate their variability. This type of modeling makes it possible to take into account individual covariates (weight, gestational age ...) to explain the pharmacokinetic variability between mother - child pairs. The final model will be validated by a simulation technique. The final model will be used to rationalize the changes in antiepileptic doses during pregnancy and to explain the differences in passage, based on individual covariates, then to perform simulations to find out how to modify the administration for treatment to be effective as often as possible.
The secondary endpoints are
- Exposure ratio (area under the concentration-time curve) between the mother and the fetus to describe the transplacental passage of levetiracetam levetiracetam.
- To correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children
- Conditions
- Epilepsy in Pregnancy
- Being tested
- biological collection
- Keywords
- Epilepsy, pharmacokinetic, levetiracetam, placental transfer.
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biological collectionBiological
Blood collection at each trimester of pregnancy, delivery and post partum visit or at medical interruption.
Collection of saliva at each trimester of pregnancy and post partum visit. Collection of cord blood and amniotic fluid at delivery or at medical interruption.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women | Other | 40 Pregnant women and 10 Pregnant women that have a medical interruption of pregnancy who were already treated by levetiracetam.
Blood collection at each trimester of pregnancy, delivery and post partum visit or at medical interruption.
Collection of saliva at each trimester of pregnancy and post partum visit. Collection of cord blood and amniotic fluid at delivery or at medical interruption Receives: Biological: biological collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levetiracetam pharmacokinetics in pregnancy
Levetiracetam concentrations as a function of time
Measured: At delivery
Secondary outcomes (9)
Levetiracetam pharmacokinetics in pregnancy
Levetiracetam concentrations as a function of time
Measured: At inclusion
Levetiracetam pharmacokinetics in pregnancy
Levetiracetam concentrations as a function of time
Measured: Until 17 weeks
Levetiracetam pharmacokinetics in pregnancy
Levetiracetam concentrations as a function of time
Measured: Until 28 weeks
Levetiracetam pharmacokinetics in pregnancy
Levetiracetam concentrations as a function of time
Measured: Until 6 week after delivery
Exposure ratio
area below the concentration curve as a function of time) between the mother and the fetus to describe the transplacental passage of levetiracetam.
Measured: At delivery
Link between levetiracetam concentrations and effects
correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children.
Measured: At inclusion
Link between levetiracetam concentrations and effects
Correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children
Measured: Until 17 weeks
Link between levetiracetam concentrations and effects
Correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children
Measured: Until 28 weeks
Link between levetiracetam concentrations and effects
Correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children.
Measured: Until 6 week after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2019
- Study start20 Apr 2022
- Primary completion16 Aug 2023
- Study completion16 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Epilepsy in PregnancyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Protocol to determine the optimal dose of levetiracetam during pregnancy
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Jean Marc Tréluyer, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04117425
- Sponsor's protocol ID
- K170404J
- Acronym
- EPICEINTE
- Status last verified
- Jun 2026
- First submitted
- 4 Jun 2019
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pennell PB. Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology. 2003 Sep 1;61(6 Suppl 2):S35-42. doi: 10.1212/wnl.61.6_suppl_2.s35.
PubMed 14504308Tomson T, Palm R, Kallen K, Ben-Menachem E, Soderfeldt B, Danielsson B, Johansson R, Luef G, Ohman I. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia. 2007 Jun;48(6):1111-6. doi: 10.1111/j.1528-1167.2007.01032.x. Epub 2007 Mar 22.
PubMed 17381438Westin AA, Reimers A, Helde G, Nakken KO, Brodtkorb E. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure. 2008 Mar;17(2):192-8. doi: 10.1016/j.seizure.2007.11.027. Epub 2008 Jan 3.
PubMed 18180176
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Maternal Pharmacokinetic and Placental Transfer of Levetiracetam
- ClinicalTrials.gov ID
- NCT04117425
- Acronym / sponsor ID
- EPICEINTE / K170404J
- Conditions
- Epilepsy in Pregnancy
- Keywords
- Epilepsy, pharmacokinetic, levetiracetam, placental transfer.
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 20 Apr 2022 (actual)
- Primary completion
- 16 Aug 2023 (actual)
- Study completion
- 16 Aug 2023 (actual)
- First posted
- 7 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypotheses: The treatment of epilepsy during pregnancy is difficult because of the risk of anti-epileptic drugs on the one hand and the risk of destabilization of epilepsy in the mother on the other hand. There is limited data on the pharmacokinetics (concentration study) and pharmacodynamics (efficacy and toxicity effects study) of levetiracetam in pregnant women. The few studies focus on few women and show very strong interindividual variability and a tendency to decrease total concentrations.
Main objective: To develop a population pharmacokinetic model of levetiracetam during pregnancy. After the study, this model could be used to propose dose adjustments to maintain stable concentrations in pregnant women throughout pregnancy.
Secondary objectives:
- Describe placental transfer during childbirth and during a medical termination of pregnancy
- Link the concentration and its variation in the individual to the effects of treatment
Detailed description
Methodology: Are included by the neurology service, pregnant women which are already under levetiracetam and / or obstetric gynecology services for her treatment of epilepsy, pregnant women at first consultation. Women are already taking levetiracetam and the drug is not provided by the study40 mother-child couples, as well as 10 women who undergo a medical termination of pregnancy will have to be included in the study, in 7 maternities in Paris.
Women are already taking the drugs, according to the practices of the different services, and the study will not change their prescriptions of these drugs. The women will have a blood sample at 3 visits during pregnancy (11-14 weeks, 24-28 weeks and 35-39 weeks) and at the post-partum consultation. At delivery, a collection of the mother, cord blood and amniotic fluid will be performed. A salivary specimen will be routinely collected at the same time as the mother's plasma sample.
The pharmaco-statistical analysis will be conducted using non-linear mixed-effect modeling programs (Monolix and Nonmem) to calculate the main pharmacokinetic parameters of the mother and fetus and to estimate their variability. This type of modeling makes it possible to take into account individual covariates (weight, gestational age ...) to explain the pharmacokinetic variability between mother - child pairs. The final model will be validated by a simulation technique. The final model will be used to rationalize the changes in antiepileptic doses during pregnancy and to explain the differences in passage, based on individual covariates, then to perform simulations to find out how to modify the administration for treatment to be effective as often as possible.
The secondary endpoints are
- Exposure ratio (area under the concentration-time curve) between the mother and the fetus to describe the transplacental passage of levetiracetam levetiracetam.
- To correlate the evolution of the concentrations in the woman (value in the woman whose treatment is balanced before the pregnancy minus the value when she is pregnant) to
- the effectiveness (number of crises that the patient did).
- tolerance: presence or absence of clinical and biological abnormalities occurring in pregnant women and children
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Protocol to determine the optimal dose of levetiracetam during pregnancy
| Arm | Type | Receives |
|---|---|---|
| Pregnant women | Other | Biological: biological collection40 Pregnant women and 10 Pregnant women that have a medical interruption of pregnancy who were already treated by levetiracetam. Blood collection at each trimester of pregnancy, delivery and post partum visit or at medical interruption. Collection of saliva at each trimester of pregnancy and post partum visit. Collection of cord blood and amniotic fluid at delivery or at medical interruption |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- pregnant Women of childbearing age who are pregnant
- Age ≥18 years
- Women with epilepsy treated with levetiracetam in monotherapy or combination
- affiliated to a social security scheme (or entitled)
Key exclusion criteria (10 listed)
- Women treated with antiepileptics for pathology other than epilepsy
- Women treated with a combination of more than 3 antiepileptics
- Severe anemia
- Renal failure (moderate to severe)
- Hepatic impairment (moderate to severe)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| biological collectionBlood collection at each trimester of pregnancy, delivery and post partum visit or at medical interruption. Collection of saliva at each trimester of pregnancy and post partum visit. Collection of cord blood and amniotic fluid at delivery or at medical interruption. | Biological | Pregnant women |
Primary outcome
Levetiracetam pharmacokinetics in pregnancy
Time frame: At delivery
Levetiracetam concentrations as a function of time
9 secondary outcomes
Levetiracetam pharmacokinetics in pregnancy
Time frame: At inclusion
Levetiracetam pharmacokinetics in pregnancy
Time frame: Until 17 weeks
Levetiracetam pharmacokinetics in pregnancy
Time frame: Until 28 weeks
Levetiracetam pharmacokinetics in pregnancy
Time frame: Until 6 week after delivery
Exposure ratio
Time frame: At delivery
Link between levetiracetam concentrations and effects
Time frame: At inclusion
Link between levetiracetam concentrations and effects
Time frame: Until 17 weeks
Link between levetiracetam concentrations and effects
Time frame: Until 28 weeks
Link between levetiracetam concentrations and effects
Time frame: Until 6 week after delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Background: PubMed 14504308Pennell PB. Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology. 2003 Sep 1;61(6 Suppl 2):S35-42. doi: 10.1212/wnl.61.6_suppl_2.s35.
- Background: PubMed 17381438Tomson T, Palm R, Kallen K, Ben-Menachem E, Soderfeldt B, Danielsson B, Johansson R, Luef G, Ohman I. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia. 2007 Jun;48(6):1111-6. doi: 10.1111/j.1528-1167.2007.01032.x. Epub 2007 Mar 22.
- Background: PubMed 18180176Westin AA, Reimers A, Helde G, Nakken KO, Brodtkorb E. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure. 2008 Mar;17(2):192-8. doi: 10.1016/j.seizure.2007.11.027. Epub 2008 Jan 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Marc Tréluyer, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing biological collection in people with Epilepsy in Pregnancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levetiracetam pharmacokinetics in pregnancy (time frame: At delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04117425, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.