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

Phase 4

• Conditions: Contraception; Drug Interactions
• Interventions: Drug: Topiramate-Implant; Drug: Implant; Drug: Carbamazepine-Implant

• Registration Number: NCT03307863
• Lead Sponsor: University of Sao Paulo

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-09-27
• Study First Submitted QC: 2017-10-10
• Study First Posted: 2017-10-12
• Study Start: 2017-11-01
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-03
• Last Update Posted: 2019-08-06
• Primary Completion: 2020-11-30
• Study Completion: 2020-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 69

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).

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Topiramate-Implant	Topiramate-Implant	Women with epilepsy using topiramate for at least 3 months will have an etonogestrel-releasing implant inserted
Implant	Implant	Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted
Carbamazepine-Implant	Carbamazepine-Implant	Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using carbamazepine	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using carbamazepine	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using carbamazepine	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using carbamazepine	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using topiramate	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Plasma maximum concentration (Cmax) of topiramate in women with epilepsy (WWE)	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of topiramate
Plasma minimum concentration (Cmin) of topiramate in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of topiramate
Time to maximum concentration (Tmax) of topiramate in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of topiramate
Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using topiramate	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Area under the plasma concentration versus time curve (AUC) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of carbamazepine
Plasma minimum concentration (Cmin) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of carbamazepine
Time to maximum concentration (Tmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of carbamazepine
Bleeding pattern associated with etonogestrel implant use	Daily for 24 weeks	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
Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using topiramate	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using topiramate	Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement	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.
Plasma maximum concentration (Cmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of carbamazepine
Area under the plasma concentration versus time curve (AUC) of topiramate in women with epilepsy (WWE) before and after ENG implant placement	Prior to implant placement and at 24 weeks of implant use	Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of topiramate

Trial Locations

Locations (1)

Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; 🇧🇷 Ribeirão Preto, Sao Paulo, Brazil