Effect of Repeat Administration of Eslicarbazepine Acetate on the Pharmacokinetics of a Combined Oral Contraceptive

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00898560
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics and tolerability of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).

Condition or Disease	Intervention/Treatment	Phase
Partial Epilepsy	Drug: eslicarbazepine acetate and Microginon®; Drug: Microginon®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Repeated Administration of Eslicarbazepine Acetate (BIA 2-093) 800mg Once-daily on the Pharmacokinetics of a Combined Oral Contraceptive in Healthy Female Subjects
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: Microginon® A single oral dose of a combined oral contraceptive containing 30ug ethinyloestradiol and 150ug levonorgestrel (Microginon ®).	Drug: Microginon®; Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)
Experimental: ESL and Microginon® 15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive.	Drug: eslicarbazepine acetate and Microginon®; eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period; Other Names: ESL BIA 2-093

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Plasma Concentration [15-day]

   To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).

Secondary Outcome Measures

1. AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification [15-day]

   To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).

2. AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity [15-day]

   To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Pre-menopausal female subjects

• Age 18-40 years, inclusive

• Body mass index (BMI) 19-30 kg/m2, inclusive

• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG

• Negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening

• Negative urine pregnancy test at screening and admission to each treatment period.

• Using one of the following methods of contraception: double barrier or intrauterine device

Exclusion Criteria:

• Subjects who have any contra-indication to the use of oral contraceptives

• History or presence of clinically relevant diseases, disorders or surgical history

• History of alcoholism or drug abuse

• Have used medicines within two weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Human Pharmacology Unit (UFH), Section of Clinical Research (SIC), Department of Research & Development (DID), BIAL - Portela & Cª, SA, S. Mamede do Coronado	Porto		Portugal	4745-457

Sponsors and Collaborators

• Bial - Portela C S.A.

Investigators

• Principal Investigator: Manuel Vaz-da-Silva, Bial Portela

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT00898560
• Other Study ID Numbers: BIA-2093-128
• First Posted: May 12, 2009
• Last Update Posted: Dec 12, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Bial - Portela C S.A.: Partial; Epilepsy; Eslicarbazepine acetate; Combined oral contraceptive; Pharmacokinetics; Tolerability
• Additional relevant MeSH terms: Epilepsy; Epilepsies, Partial; Eslicarbazepine acetate

Study Results

Participant Flow

Arm/Group Title	ESL and Microginon®
Arm/Group Description	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
Period Title: Overall Study
STARTED	20
COMPLETED	19
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	ESL and Microginon®
Arm/Group Description	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Plasma Concentration
Description	To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time Frame	15-day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Microginon®	ESL and Microginon®
Arm/Group Description	A single oral dose of a combined oral contraceptive containing 30ug ethinyloestradiol and 150ug levonorgestrel (Microginon ®). Microginon®: Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
Measure Participants	19	19
Cmax (ethinyloestradiol)	82.4 (23.4)	75.0 (26.8)
Cmax (levonogestrel)	4170 (1720)	4340 (1530)

2. Secondary Outcome

Title	AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification
Description	To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time Frame	15-day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Microginon®	ESL and Microginon®
Arm/Group Description	A single oral dose of a combined oral contraceptive containing 30ug ethinyloestradiol and 150ug levonorgestrel (Microginon ®). Microginon®: Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
Measure Participants	19	19
AUC0-t (ethinyloestradiol)	0.665 (0.195)	0.453 (0.167)
AUC0-t (levonogestrel)	37.4 (19.1)	32.0 (12.9)

3. Secondary Outcome

Title	AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
Description	To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel).
Time Frame	15-day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Microginon®	ESL and Microginon®
Arm/Group Description	A single oral dose of a combined oral contraceptive containing 30ug ethinyloestradiol and 150ug levonorgestrel (Microginon ®). Microginon®: Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period
Measure Participants	19	19
AUC0-∞ (ethinyloestradiol)	0.768 (0.223)	0.533 (0.181)
AUC0-∞ (levonorgestrel)	52.1 (22.1)	43.1 (13.3)

Adverse Events

Arm/Group Title	ESL and Microginon®		Microginon®
Arm/Group Description	15-day treatment with ESL 800 mg once daily, with co administration of a single oral dose of Microginin® on Day 14 of the relevant dosing period, to assess impact of ESL on pharmacokinetics of the combined oral contraceptive. eslicarbazepine acetate and Microginon®: eslicarbazepine acetate: once-daily oral dose of 800 mg on days 1- 15 of treatment period. Microginon®: single oral dose on day 14 of treatment period		A single oral dose of a combined oral contraceptive containing 30ug ethinyloestradiol and 150ug levonorgestrel (Microginon ®). Microginon®: Single oral dose of Microginon® (30ug ethinyloestradiol and 150ug levonorgestrel)
All Cause Mortality
	ESL and Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ESL and Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	ESL and Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/20 (90%)		8/20 (40%)
Eye disorders
Xerophthalmia	2/20 (10%)		0/20 (0%)
Gastrointestinal disorders
Constipation	1/20 (5%)		0/20 (0%)
Dry throat	1/20 (5%)		0/20 (0%)
Dyspepsia	1/20 (5%)		0/20 (0%)
Hypoaesthesia oral	2/20 (10%)		0/20 (0%)
Nausea	5/20 (25%)		0/20 (0%)
Paraesthesia oral	5/20 (25%)		0/20 (0%)
Toothache	0/20 (0%)		1/20 (5%)
Vomiting	2/20 (10%)		0/20 (0%)
General disorders
Vessel puncture site haematoma	0/20 (0%)		1/20 (5%)
Infections and infestations
Upper respiratory tract infection	4/20 (20%)		1/20 (5%)
Injury, poisoning and procedural complications
Heat stroke	1/20 (5%)		0/20 (0%)
Investigations
Blood creatine phosphokinase increased	2/20 (10%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/20 (5%)		0/20 (0%)
Joint range of motion decreased	2/20 (10%)		0/20 (0%)
Musculoskeletal pain	1/20 (5%)		0/20 (0%)
Nervous system disorders
Diplopia	1/20 (5%)		0/20 (0%)
Dizziness	5/20 (25%)		0/20 (0%)
Headache	6/20 (30%)		2/20 (10%)
Somnolence	8/20 (40%)		2/20 (10%)
Syncope	1/20 (5%)		0/20 (0%)
Tremor	1/20 (5%)		0/20 (0%)
Psychiatric disorders
Anxiety	1/20 (5%)		0/20 (0%)
Libido increased	1/20 (5%)		0/20 (0%)
Renal and urinary disorders
Dysuria	1/20 (5%)		0/20 (0%)
Reproductive system and breast disorders
Metrorrhagia	0/20 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	1/20 (5%)		0/20 (0%)
Cough	0/20 (0%)		2/20 (10%)
Throat irritation	1/20 (5%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Cheilitis	1/20 (5%)		0/20 (0%)
Rash macular	1/20 (5%)		0/20 (0%)
Social circumstances
Sexual activity increased	1/20 (5%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.