Effect of Anti-epileptic Drugs on Etonogestrel-releasing Implant Pharmacokinetics in Women With Epilepsy

Study Overview
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Brief Summary
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Data on the interaction between the etonogestrel (ENG) implant and antiepileptic drug (AED) regimen are scarce. We will evaluated the effect of 2 AED regimens (1 including carbamazepine and the other topiramate) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in women with epilepsy.

Official Title
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Effect of Anti-epileptic Drugs on Etonogestrel-releasing Implant Pharmacokinetics in Women With Epilepsy

Conditions
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Contraception, Drug Interactions

Intervention / Treatment
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* Drug: Carbamazepine-Implant
* Drug: Topiramate-Implant
* Drug: Implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women 18- 45 years old; with regular menstrual cycles; with BMI between 18 and 29.9 (kg/m2); who has selected the ENG implant as a contraceptive method; Using a stable antiepileptic drug regimen including carbamazepine or topiramate for ate least 3 months (only for women with epilepsy). Exclusion Criteria: use of short-acting hormonal contraceptives in the month prior to enrollment; use of depomedroxyprogesterone acetate in the 6 months prior to enrollment; women with conditions classified as category 3 and/or 4 for etonogestrel implant use according to the World Health Organization Medical Eligibility Criteria for contraceptive use; drug or alcohol addiction; use of other drugs metabolized by CYP3A4 30 days prior to enrollment; non adherence to antiepileptic drug regimen (only for women with epilepsy); illiteracy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: It is a non-randomized clinical trial (controlled clinical trial)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbamazepine-Implant<br>Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted | Drug: Carbamazepine-Implant<br>* Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted<br>|
| Experimental: Topiramate-Implant<br>Women with epilepsy using topiramate for at least 3 months will have an etonogestrel-releasing implant inserted | Drug: Topiramate-Implant<br>* Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted<br>|
| Active Comparator: Implant<br>Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted | Drug: Implant<br>* Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using carbamazepine | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for area under the curve evaluation of ENG (AUC, 0-24 weeks). The plasma ENG AUC will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using carbamazepine | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmax of ENG. The plasma ENG Cmax will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using carbamazepine | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmin of ENG. The plasma ENG Cmin will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using carbamazepine | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of Tmax of ENG. The Tmax of ENG will be compared to that of women without epilepsy and without carbamazepine use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding pattern associated with etonogestrel implant use | Bleeding pattern (frequency, duration and number of bleeding/spotting days) associated with etonogestrel implant use will be evaluated in WWE using carbamazepine or topiramate and in women without epilepsy and without antiepileptic drug use | Daily for 24 weeks | 
| Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using topiramate | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for area under the curve evaluation of ENG (AUC, 0-24 weeks). The plasma ENG AUC will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using topiramate | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmax of ENG. The plasma ENG Cmax will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using topiramate | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of plasma Cmin of ENG. The plasma ENG Cmin will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using topiramate | Blood will be collected prior to ENG implant insertion and each 15 days for 24 weeks after implant placement for evaluation of Tmax of ENG. The Tmax of ENG will be compared to that of women without epilepsy and without topiramate use prior to ENG implant insertion and each 15 days for 24 weeks after implant placement. | Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement | 
| Area under the plasma concentration versus time curve (AUC) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of carbamazepine | Prior to implant placement and at 24 weeks of implant use | 
| Plasma maximum concentration (Cmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of carbamazepine | Prior to implant placement and at 24 weeks of implant use | 
| Plasma minimum concentration (Cmin) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of carbamazepine | Prior to implant placement and at 24 weeks of implant use | 
| Time to maximum concentration (Tmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of carbamazepine | Prior to implant placement and at 24 weeks of implant use | 
| Area under the plasma concentration versus time curve (AUC) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of topiramate | Prior to implant placement and at 24 weeks of implant use | 
| Plasma maximum concentration (Cmax) of topiramate in women with epilepsy (WWE) | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of topiramate | Prior to implant placement and at 24 weeks of implant use | 
| Plasma minimum concentration (Cmin) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of topiramate | Prior to implant placement and at 24 weeks of implant use | 
| Time to maximum concentration (Tmax) of topiramate in women with epilepsy (WWE) before and after ENG implant placement | Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of topiramate | Prior to implant placement and at 24 weeks of implant use | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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etonogestrel implant, anti-epileptic drugs, pharmacokinetics