Women With Epilepsy: a Pilot Study of PK and PD Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users

Epilepsy Clinical Trial

— WESAIL  

Official title:

Women With Epilepsy: a Pilot Study of Pharmacokinetic and Pharmacodynamic Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02362373
• Other study ID #: AAAI0750
• Status: Completed
• Phase: Phase 4
• First received: February 9, 2015
• Last updated: December 14, 2015
• Start date: August 2011
• Est. completion date: January 2014

Study information

• Verified date: December 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators will conduct a prospective, seven-month pilot study to explore pharmacokinetic (PK) and pharmacodynamic (PD) effects among women with epilepsy using the levonorgestrel intrauterine system (LNG IUS) for contraception. The investigators will enroll twenty women with well-controlled epilepsy maintained on stable anti-epileptic drugs (AED) therapy seeking the LNG IUS for contraception. The primary outcomes are AED levels and seizures before and after LNG IUS placement. Secondary outcomes include LNG levels, evidence of ovulation three weeks after insertion (serum progesterone >3ng/ml), bleeding and spotting, endometrial thickness, continuation, satisfaction and adverse events (removals, expulsions, side effects). The investigators will conduct a baseline month assessment, insertion visit, and follow-up visits at 21 days, three months and six months.

Description:

Study Procedures This pilot study consists of five study visits. Once preliminary eligibility is determined through a telephone screening interview, the first visit is scheduled.

Visit 1 Enrollment/Baseline

• Review Eligibility

• Informed Consent

• Collect Baseline Information

• Vital Signs

• Pregnancy Test

• Complete Physical Exam including Pelvic exam,

• Chlamydia testing, and a Pap test if needed as per ASCCP (American Society for Colposcopy and Cervical Pathology) guidelines

• Receive diary to record any bleeding or spotting

• Receive condoms, if needed, for use until IUS insertion

• Sign release for contact of primary neurologist or epileptologist

• Study MD to contact participant's neurologist to notify of trial participation, and verify type and dose of AEDs

Visit 2 Insertion/4-6 Weeks from Baseline

• Vital Signs

• Pregnancy Test

• Phlebotomy for hormone and AED levels

• Transvaginal ultrasound

• IUS Insertion

• Review and collect completed diary

• Receive new diary

Visit 3/ Follow up 3 Weeks post IUS Insertion

• Vital Signs

• Phlebotomy for hormone and AED levels

• Transvaginal Ultrasound

• Review and collect completed diary

• Receive new diary

Visit 4/Follow up 3 Months post IUS Insertion

• Vital Signs

• Phlebotomy for hormone and AED levels

• Transvaginal ultrasound

• Review and collect completed diary

• Receive new diary

• Acceptability Questionnaire

Visit 5/ Exit 6 Months post IUS insertion

• Vital Signs

• Phlebotomy for hormone and AED levels

• Transvaginal Ultrasound

• Review and collect final completed diary

• Acceptability Questionnaire

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Age18-45 years

2. Regular menstrual cycle of length 21-35 days

3. Willing to use IUS for contraception

4. Willing to use non-hormonal contraception for one month before insertion

5. Stable AED therapy for at least two months

6. Well-controlled epilepsy (2 or fewer seizures, other than simple partial, per month)

7. Working telephone

8. English Speaking

Exclusion Criteria:

1. Current pregnancy or pregnancy in the previous two months

2. Breastfeeding with amenorrhea

3. Hepatic p450 enzyme inducing medications other than AEDs (griseofulvin, rifampin, St. John's Wort, bosentan)

4. Depomedroxyprogesterone acetate within previous six months

5. Congenital or acquired uterine anomaly, including myomas, that distort the uterine cavity

6. Acute pelvic infection or a history pelvic infection without subsequent intrauterine pregnancy

7. Postpartum endometritis or infected abortion in the last three months

8. Genital bleeding of unknown etiology

9. Untreated lower genital tract infection (cervical or vaginal)

10. Acute liver disease or liver tumor, benign or malignant

11. HIV infection or partner with HIV infection

12. Increased susceptibility to pelvic infection

13. A previously inserted intrauterine device (IUD) that has not been removed

14. Hypersensitivity to any component of the LNG IUS

15. Known or suspected carcinoma of the breast

16. Current abnormal cervical cytology other than ASCUS or a history of abnormal cervical cytology other than ASCUS without appropriate follow-up demonstrating no evidence of disease

17. History of genital tract malignancy

18. Current use of anti-coagulants

19. Current alcoholism or drug abuse

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Contraception
• Epilepsy

Intervention

Drug:
• levonorgestrel IUS
placement of levonorgestrel intrauterine system

Locations

Country	Name	City	State
United States	Columbia University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level	The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of lamotrigine after IUD insertion.	from baseline to 6 months after LNG IUS insertion	Yes
Primary	Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Level	The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of levetiracetam after IUD insertion.	from baseline to 6 months after LNG IUS insertion	Yes
Primary	Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Level	The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of oxcarbazepine after IUD insertion.	from baseline to 6 months after LNG IUS insertion	Yes
Secondary	Change in Seizure Frequency	Number of participants with increased, unchanged or decreased mean monthly seizure frequency.	baseline to 6 months	No
Secondary	Number of Participants Continuing With IUD	Women continuing the IUD for contraception at 6 months	6 months	No