Effect of BIA 2-093 on the Pharmacokinetics of a Combined Oral Contraceptive.

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02281448
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

Single centre, two-way crossover, randomised, open-label study in 20 healthy female volunteers.The volunteers received an oral single-dose of a combined contraceptive containing with an oral once daily dose of 1200 mg of BIA 2-093

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: BIA 2-093; Drug: Contraceptives, Oral, Combined	Phase 1

Detailed Description

Single centre, two-way crossover, randomised, open-label study in 20 healthy female volunteers.The volunteers received an oral single-dose of a combined contraceptive containing 30 μg ethinyloestradiol and 150 μg levonorgestrel on two occasions - once as such and once after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 for 15 days separated by a washout period of at least 3 weeks.

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 BIA 2-093 on the Pharmacokinetics of a Combined Oral Contraceptive in Healthy Female Volunteers
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: May 1, 2005
• Actual Study Completion Date: May 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment sequence A oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days followed by washout and 3 days of oral single-dose contraceptive	Drug: BIA 2-093; Drug: Contraceptives, Oral, Combined
Other: Treatment sequence B oral single-dose of a contraceptive for 3 days after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days	Drug: BIA 2-093; Drug: Contraceptives, Oral, Combined

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Plasma BIA 2-194 Concentration [Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.]

   Cmax - Maximum observed plasma BIA 2-194 concentration on days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.

Secondary Outcome Measures

1. Cmax [pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.]

   Cmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)

2. Tmax [pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.]

   Tmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)

3. AUC0-t [pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.]

   AUC0-t (ng.h/mL) following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pre-menopausal female;

• Able and willing to give written informed consent;

• Aged 18 to 40 years, inclusive;

• Not pregnant or breast-feeding;

• Body mass index (BMI) between 19 and 30 kg/m2, inclusive;

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

• Clinical laboratory tests with clinically acceptable results at screening and admission to the first period;

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

• Negative test for drugs of abuse at screening;

• Non-smoker or smokes less than 10 cigarettes or equivalent per day;

• Agreed to either practice abstinence or use a double-barrier or intra-uterine device from screening until the follow-up visit;

• Negative pregnancy test at screening and admission to the first period.

Exclusion Criteria:

• Had any contra-indication to the use of oral contraceptives;

• Had experienced notable adverse events while on any oral contraceptive;

• Had a history of alcoholism or drug abuse;

• Had a relevant history or presence of respiratory, gastrointestinal, renal, hepatic,haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders;

• Had acute gastrointestinal symptoms at the time of screening or admission to the first period;

• Had a significant infection or inflammatory process at the time of screening or admission to the first period;

• Had a relevant surgical history;

• Had a relevant family history;

• Had a history of relevant drug hypersensitivity (e.g., carbamazepine or oxcarbazepine);

• Had used relevant prescription or over-the-counter medication within 2 weeks ofadmission to the first period;

• Consumed more than 14 units of alcohol a week;

• Had participated in any clinical trial within 3 months prior to screening;

• Had previously received BIA 2-093;

• Had donated or received any blood or blood products within 2 months prior to screening;

• Was unlikely to co-operate with the requirements of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BIAL - Portela & Cª, S.A.	S. Mamede do Coronado		Portugal	4045-457

Sponsors and Collaborators

• Bial - Portela C S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT02281448
• Other Study ID Numbers: BIA-2093-114
• First Posted: Nov 2, 2014
• Last Update Posted: Dec 3, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Epilepsy; Eslicarbazepine acetate; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined

Study Results

Participant Flow

Arm/Group Title	Treatment Sequence A	Treatment Sequence B
Arm/Group Description	oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days followed by washout and 3 days of oral single-dose contraceptive BIA 2-093 Contraceptives, Oral, Combined	oral single-dose of a contraceptive for 3 days after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days BIA 2-093 Contraceptives, Oral, Combined
Period Title: Overall Study
STARTED	10	10
COMPLETED	8	9
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Treatment Sequence A	Treatment Sequence B	Total
Arm/Group Description	oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days followed by washout and 3 days of oral single-dose contraceptive BIA 2-093 Contraceptives, Oral, Combined	oral single-dose of a contraceptive for 3 days after pre-treatment with an oral once daily dose of 1200 mg of BIA 2-093 plus single-dose of a contraceptive for 15 days BIA 2-093 Contraceptives, Oral, Combined	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 100%	10 100%	20 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Plasma BIA 2-194 Concentration
Description	Cmax - Maximum observed plasma BIA 2-194 concentration on days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.
Time Frame	Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cmax (BIA 2-194)
Arm/Group Description	Mean trough (pre-dose) plasma concentrations of BIA 2-194 on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.
Measure Participants	17
Day 1	0.00 (0.00)
Day 2	8443 (1422)
Day 4	10691 (1736)
Day 6	10961 (1737)
Day 8	10175 (996)
Day 10	10332 (1470)
Day 12	10821 (1806)
Day 14	10670 (1447)
Day 15	9978 (1452)

2. Secondary Outcome

Title	Cmax
Description	Cmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time Frame	pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Population
Arm/Group Description	Overall population - 17 subjects
Measure Participants	17
Cmax (ethinyloestradiol) Test	53.4 (17.9)
Cmax (ethinyloestradiol) Reference	66.1 (19.1)
Cmax (Levonorgestrel) Test	3220 (1330)
Cmax (Levonorgestrel) Reference	3720 (1540)

3. Secondary Outcome

Title	Tmax
Description	Tmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time Frame	pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Population
Arm/Group Description	Overall population - 17 subjects
Measure Participants	17
tmax (ethinyloestradiol) Test	1.67 (0.53)
tmax (ethinyloestradiol) Reference	1.52 (0.21)
tmax (Levonorgestrel) Test	1.28 (0.49)
tmax (Levonorgestrel) Reference	1.21 (0.36)

4. Secondary Outcome

Title	AUC0-t
Description	AUC0-t (ng.h/mL) following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference)
Time Frame	pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Population
Arm/Group Description	Overall population - 17 subjects
Measure Participants	17
AUC0-t (ethinyloestradiol) Test	347 (145)
AUC0-t (ethinyloestradiol) Reference	595 (639)
AUC0-t (Levonorgestrel) Test	24000 (12100)
AUC0-t (Levonorgestrel) Reference	33600 (20000)

Adverse Events

Arm/Group Title	Eslicarbazepine Acetate 1200 mg + Microginon®		Microginon®
Arm/Group Description	Eslicarbazepine acetate 1200 mg + Microginon® (n=19)		Microginon® (n=18)
All Cause Mortality
	Eslicarbazepine Acetate 1200 mg + Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Eslicarbazepine Acetate 1200 mg + Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/20 (0%)
Infections and infestations
Abnormal values of neutrophils and white blood cells	1/20 (5%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Eslicarbazepine Acetate 1200 mg + Microginon®		Microginon®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/19 (100%)		5/18 (27.8%)
Cardiac disorders
Palpitations	3/19 (15.8%)		0/18 (0%)
Eye disorders
Eyelid oedema	1/19 (5.3%)		0/18 (0%)
Gastrointestinal disorders
Abdominal colic	1/19 (5.3%)		0/18 (0%)
Change in bowel habits	1/19 (5.3%)		0/18 (0%)
Constipation	5/19 (26.3%)		1/18 (5.6%)
Dry mouth	1/19 (5.3%)		0/18 (0%)
Dyspepsia	1/19 (5.3%)		0/18 (0%)
Epigastric fullness	1/19 (5.3%)		0/18 (0%)
Gastroenteritis noninfectious	1/19 (5.3%)		0/18 (0%)
Nausea	5/19 (26.3%)		0/18 (0%)
Vomiting	1/19 (5.3%)		0/18 (0%)
Xerostomia	1/19 (5.3%)		0/18 (0%)
General disorders
Flu-like symptoms	1/19 (5.3%)		0/18 (0%)
Increased thirst	3/19 (15.8%)		0/18 (0%)
Thirst	1/19 (5.3%)		0/18 (0%)
Infections and infestations
Escherichia coli cystitis	0/19 (0%)		1/18 (5.6%)
Viral infection	1/19 (5.3%)		0/18 (0%)
Pharyngitis	1/19 (5.3%)		0/18 (0%)
Respiratory tract infection	1/19 (5.3%)		0/18 (0%)
Injury, poisoning and procedural complications
Catheter site ecchymosis	3/19 (15.8%)		0/18 (0%)
Catheter site haematoma	1/19 (5.3%)		0/18 (0%)
Investigations
CPK increased	1/19 (5.3%)		0/18 (0%)
Lymph node palpable	1/19 (5.3%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/19 (5.3%)		0/18 (0%)
Nervous system disorders
Concentration impairment	1/19 (5.3%)		0/18 (0%)
Dizziness	10/19 (52.6%)		0/18 (0%)
Facial paraesthesia	1/19 (5.3%)		0/18 (0%)
Frontal headache	1/19 (5.3%)		0/18 (0%)
Headache	4/19 (21.1%)		1/18 (5.6%)
Incoordination	1/19 (5.3%)		0/18 (0%)
Lightheadedness	1/19 (5.3%)		0/18 (0%)
Paraesthesia lips	3/19 (15.8%)		0/18 (0%)
Paraesthesia tongue	1/19 (5.3%)		0/18 (0%)
Pre-syncope	0/19 (0%)		1/18 (5.6%)
Somnolence	14/19 (73.7%)		0/18 (0%)
Tremor of hands	1/19 (5.3%)		0/18 (0%)
Vasovagal reaction	2/19 (10.5%)		1/18 (5.6%)
Reproductive system and breast disorders
Dysmenorrhea	0/19 (0%)		1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/19 (5.3%)		0/18 (0%)
Cough	2/19 (10.5%)		0/18 (0%)
Dry throat	1/19 (5.3%)		0/18 (0%)
Pain chest	1/19 (5.3%)		0/18 (0%)
Pharyngitis	1/19 (5.3%)		0/18 (0%)
Rhinitis	1/19 (5.3%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Acneiform eruption	1/19 (5.3%)		0/18 (0%)
Erythema facial	1/19 (5.3%)		0/18 (0%)
Erythematous eruption	1/19 (5.3%)		0/18 (0%)
Erythematous rash	2/19 (10.5%)		0/18 (0%)
Generalized macular rash	1/19 (5.3%)		0/18 (0%)
Localized erythema	1/19 (5.3%)		0/18 (0%)
Night sweats	1/19 (5.3%)		0/18 (0%)
Pruritus	1/19 (5.3%)		0/18 (0%)
Scalp pain	0/19 (0%)		1/18 (5.6%)

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.