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

Primary Purpose

Contraception, Drug Interactions

Status
Unknown status
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Carbamazepine-Implant
Topiramate-Implant
Implant
Sponsored by
University of Sao Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Contraception focused on measuring etonogestrel implant, anti-epileptic drugs, pharmacokinetics

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina de Ribeirão Preto da Universidade de São PauloRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Carbamazepine-Implant

Topiramate-Implant

Implant

Arm Description

Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted

Women with epilepsy using topiramate for at least 3 months will have an etonogestrel-releasing implant inserted

Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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
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.
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.
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.
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.
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
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
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
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
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
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
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
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

Full Information

First Posted
September 27, 2017
Last Updated
August 3, 2019
Sponsor
University of Sao Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT03307863
Brief Title
Effect of Anti-epileptic Drugs on Etonogestrel-releasing Implant Pharmacokinetics in Women With Epilepsy
Official Title
Effect of Anti-epileptic Drugs on Etonogestrel-releasing Implant Pharmacokinetics in Women With Epilepsy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
November 30, 2020 (Anticipated)
Study Completion Date
November 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Contraception, Drug Interactions
Keywords
etonogestrel implant, anti-epileptic drugs, pharmacokinetics

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
It is a non-randomized clinical trial (controlled clinical trial)
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
69 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Carbamazepine-Implant
Arm Type
Experimental
Arm Description
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
Arm Title
Topiramate-Implant
Arm Type
Experimental
Arm Description
Women with epilepsy using topiramate for at least 3 months will have an etonogestrel-releasing implant inserted
Arm Title
Implant
Arm Type
Active Comparator
Arm Description
Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted
Intervention Type
Drug
Intervention Name(s)
Carbamazepine-Implant
Intervention Description
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
Intervention Type
Drug
Intervention Name(s)
Topiramate-Implant
Intervention Description
Women with epilepsy using carbamazepine for at least 3 months will have an etonogestrel-releasing implant inserted
Intervention Type
Drug
Intervention Name(s)
Implant
Intervention Description
Women without epilepsy and not using an anti-epileptic drug will have an etonogestrel-releasing implant inserted
Primary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using carbamazepine
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using carbamazepine
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using carbamazepine
Description
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 Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using carbamazepine
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Secondary Outcome Measure Information:
Title
Bleeding pattern associated with etonogestrel implant use
Description
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
Time Frame
Daily for 24 weeks
Title
Area under the plasma concentration versus time curve (AUC) of ENG in women with epilepsy (WWE) using topiramate
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Plasma maximum concentration (Cmax) of ENG in women with epilepsy (WWE) using topiramate
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Plasma minimum concentration (Cmin) of ENG in women with epilepsy (WWE) using topiramate
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Time to maximum concentration (Tmax) of ENG in women with epilepsy (WWE) using topiramate
Description
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.
Time Frame
Prior to etonogestrel implant insertion and each 15 days for 24 weeks after implant placement
Title
Area under the plasma concentration versus time curve (AUC) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of carbamazepine
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Plasma maximum concentration (Cmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of carbamazepine
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Plasma minimum concentration (Cmin) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of carbamazepine
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Time to maximum concentration (Tmax) of carbamazepine in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of carbamazepine
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Area under the plasma concentration versus time curve (AUC) of topiramate in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate AUC (0-8 hours) of topiramate
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Plasma maximum concentration (Cmax) of topiramate in women with epilepsy (WWE)
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmax of topiramate
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Plasma minimum concentration (Cmin) of topiramate in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Cmin of topiramate
Time Frame
Prior to implant placement and at 24 weeks of implant use
Title
Time to maximum concentration (Tmax) of topiramate in women with epilepsy (WWE) before and after ENG implant placement
Description
Blood will be collected prior to etonogestrel implant use and at 24 weeks of its placement to evaluate Tmax of topiramate
Time Frame
Prior to implant placement and at 24 weeks of implant use
Other Pre-specified Outcome Measures:
Title
Acceptability
Description
A questionnaire will be used to measure acceptability to etonogestrel implant by WWE
Time Frame
At 24 weeks of implant placement
Title
Satisfaction
Description
A questionnaire will be applied to measure satisfaction of WWE with etonogestrel implant
Time Frame
At 24 weeks of implant placement

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carolina S Vieira, MD
Phone
+5536022818
Email
carol.sales@usp.br
First Name & Middle Initial & Last Name or Official Title & Degree
Leticia S Ferreira, MD
Phone
+553491924258
Email
lelezinhasanchez1@yahoo.com.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carolina S Vieira, MD
Organizational Affiliation
University of Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
City
Ribeirão Preto
State/Province
Sao Paulo
ZIP/Postal Code
14049-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolina S Vieira, MD
Phone
+551636022818
Email
carol.sales@usp.br
First Name & Middle Initial & Last Name & Degree
Leticia S Ferreira, MD
Phone
+553491924258
Email
lelezinhasanchez1@yahoo.com.br
First Name & Middle Initial & Last Name & Degree
Carolina S Vieira, MD

12. IPD Sharing Statement

Learn more about this trial

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

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