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

Contraception Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03307863
• Other study ID #: 2.140.103
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2017
• Est. completion date: November 30, 2020

Study information

• Verified date: August 2019
• Source: University of Sao Paulo
• Contact: Carolina S Vieira, MD
• Phone: +5536022818
• Email: carol.sales[@]usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: November 30, 2020
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Contraception
• Drug Interactions
• Epilepsy

Intervention

Drug:
• Carbamazepine-Implant
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
• Topiramate-Implant
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
• Implant
Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acceptability	A questionnaire will be used to measure acceptability to etonogestrel implant by WWE	At 24 weeks of implant placement
Other	Satisfaction	A questionnaire will be applied to measure satisfaction of WWE with etonogestrel implant	At 24 weeks of implant placement
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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