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

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.

Study Overview

• Status: Suspended
• Conditions: Contraception; Drug Interactions
• Intervention / Treatment: Drug: Carbamazepine-Implant; Drug: Topiramate-Implant; Drug: Implant

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirão Preto, Sao Paulo, Brazil, 14049-900
      • Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability	A questionnaire will be used to measure acceptability to etonogestrel implant by WWE	At 24 weeks of implant placement
Satisfaction	A questionnaire will be applied to measure satisfaction of WWE with etonogestrel implant	At 24 weeks of implant placement

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Carolina S Vieira, MD, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetics; anti-epileptic drugs; etonogestrel implant
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Sodium Channel Blockers; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Anticonvulsants; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Topiramate; Carbamazepine
• Other Study ID Numbers: 2.140.103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No