Disposition of Eslicarbazepine Acetate and Its Metabolites S-licarbazepine and R-licarbazepine

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02281591
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 4
• Duration (Days): 30
• Patients Per Site Per Month: 32.5

Study Details

Study Description

Brief Summary

Single centre, open-label, randomised study in four parallel groups of healthy volunteers

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: BIA 2-093; Drug: S-licarbazepine; Drug: R-licarbazepine	Phase 1

Detailed Description

Single centre, open-label, randomised study in four parallel groups of healthy volunteers:

Group 1 = 900 mg of eslicarbazepine acetate (ESL, BIA 2-093); Group 2 = 450 mg of S-licarbazepine plus 450 mg of R-licarbazepine; Group 3 = 450 mg of S-licarbazepine; Group 4 = 450 mg of Rlicarbazepine. In each group, the study consisted of a single-dose period (Phase

1. followed by a repeateddose period of 7 days of duration in which the investigational product was administered once daily (Phase B). The repeated-dose phase started 96 h post single-dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Disposition of Eslicarbazepine Acetate and Its Metabolites S-licarbazepine and R-licarbazepine Following Oral Administration in Healthy Volunteers
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jul 1, 2006
• Actual Study Completion Date: Jul 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: eslicarbazepine acetate 900mg of eslicarbazepine acetate (ESL, BIA 2-093)	Drug: BIA 2-093; Tablets containing 900 mg
Active Comparator: S-licarbazepine R-licarbazepine 450 mg of S-licarbazepine plus 450 mg of R-licarbazepine	Drug: S-licarbazepine; capsules containing 225 mg; Drug: R-licarbazepine; capsules containing 225 mg
Active Comparator: S-licarbazepine 450 mg of S-licarbazepine	Drug: S-licarbazepine; capsules containing 225 mg
Active Comparator: R-licarbazepine 450 mg of Rlicarbazepine	Drug: R-licarbazepine; capsules containing 225 mg

Outcome Measures

Primary Outcome Measures

1. Cmax - the Maximum Plasma Concentration [Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.]

2. Tmax - the Time of Occurrence of Cmax [Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.]

3. AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity [Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.]

Secondary Outcome Measures

1. AUC0-t - the Area Under the Plasma Concentration-time Curve to Last Measurable Time Point [Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Male or female subjects aged between 18 and 45 years, inclusive.

• Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.

• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, neurological examination, and 12-lead ECG.

• Subjects who had clinical laboratory tests clinically acceptable at screening and admission.

• Subjects who had negative tests for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab at screening.

• Subjects who were negative for drugs of abuse and alcohol at screening and admission.

• Subjects who were non-smokers or who smoke < 10 cigarettes or equivalent per day.

• Subjects who are able and willing to give written informed consent.

• (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier, intrauterine device or abstinence.

• (If female) She had a negative pregnancy test at screening and admission to Phase A.

Exclusion Criteria:

• Subjects who did not conform to the above inclusion criteria, OR

• Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders.

• Subjects who had a clinically relevant surgical history.

• Subjects who had a clinically relevant family history.

• Subjects who had a history of relevant atopy.

• Subjects who had a history of relevant drug hypersensitivity (especially carbamazepine or oxcarbazepine).

• Subjects who had a history of alcoholism or drug abuse.

• Subjects who consumed more than 14 units of alcohol a week.

• Subjects who had a significant infection or known inflammatory process on screening or admission.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scope International Life Sciences AG,	Hamburg		Germany	D-22525

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: NCT02281591
• Other Study ID Numbers: BIA-2093-115
• First Posted: Nov 2, 2014
• Last Update Posted: Dec 3, 2014
• Last Verified: Nov 1, 2014

• Additional relevant MeSH terms: Epilepsy; Eslicarbazepine acetate

Study Results

Participant Flow

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
Period Title: Overall Study
STARTED	8	8	8	8
COMPLETED	8	8	8	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine	Total
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg	Total of all reporting groups
Overall Participants	8	8	8	8	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	8 100%	8 100%	32 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 50%	4 50%	4 50%	4 50%	16 50%
Male	4 50%	4 50%	4 50%	4 50%	16 50%

Outcome Measures

1. Primary Outcome

Title	Cmax - the Maximum Plasma Concentration
Time Frame	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
Measure Participants	8	8	8	8
Cmax (BIA 2-194)	15809 (3183)	10496 (1432)	10364 (3352)	437 (143)
Cmax (BIA 2-195)	222 (68.4)	8099 (1258)	132 (29.6)	6941 (1054)
Cmax (Oxcarbazepine)	136 (25.1)	261 (53.5)	92.8 (21.8)	101 (28.6)

2. Primary Outcome

Title	Tmax - the Time of Occurrence of Cmax
Time Frame	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
Measure Participants	8	8	8	8
tmax (BIA 2-194)	1.99 (0.916)	1.01 (0.320)	0.965 (0.496)	10.7 (3.69)
tmax (BIA 2-195)	18.6 (4.14)	1.41 (0.320)	11.7 (3.77)	1.22 (0.582)
tmax (Oxcarbazepine)	3.59 (1.61)	1.34 (0.354)	1.36 (1.44)	1.21 (0.641)

3. Primary Outcome

Title	AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
Time Frame	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
Measure Participants	8	8	8	8
AUC0-∞ (BIA 2-194)	271191 (47416)	201409 (37377)	132724 (20175)	11003 (4476)
AUC0-∞ (BIA 2-195)	8816 (2168)	116884 (22425)	5417 (824)	66087 (16072)
AUC0-∞ (Oxcarbazepine)	3181 (1078)	4726 (1163)	2500 (1923)	1073 (793)

4. Secondary Outcome

Title	AUC0-t - the Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
Time Frame	Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eslicarbazepine Acetate	S-licarbazepine R-licarbazepine	S-licarbazepine	R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg	450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg	450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg	450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
Measure Participants	8	8	8	8
AUC0-t (BIA 2-194)	268045 (46861)	198313 (38771)	130147 (19326)	9419 (4707)
AUC0-t (BIA 2-195)	6757 (2211)	114635 (21741)	3074 (1001)	65203 (16161)
AUC0-t (Oxcarbazepine)	1947 (757)	3401 (902)	748 (308)	422 (247)

Adverse Events

Arm/Group Title	Eslicarbazepine Acetate		S-licarbazepine R-licarbazepine		S-licarbazepine		R-licarbazepine
Arm/Group Description	900mg of eslicarbazepine acetate (ESL, BIA 2-093) BIA 2-093: Tablets containing 900 mg		450 mg of S-licarbazepine plus 450 mg of R-licarbazepine S-licarbazepine: capsules containing 225 mg R-licarbazepine: capsules containing 225 mg		450 mg of S-licarbazepine S-licarbazepine: capsules containing 225 mg		450 mg of Rlicarbazepine R-licarbazepine: capsules containing 225 mg
All Cause Mortality
	Eslicarbazepine Acetate		S-licarbazepine R-licarbazepine		S-licarbazepine		R-licarbazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Eslicarbazepine Acetate		S-licarbazepine R-licarbazepine		S-licarbazepine		R-licarbazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Eslicarbazepine Acetate		S-licarbazepine R-licarbazepine		S-licarbazepine		R-licarbazepine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/8 (75%)		8/8 (100%)		4/8 (50%)		5/8 (62.5%)
Eye disorders
Burning sensation in eye	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Visual disturbance	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Dry mouth	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Nausea	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Numbness of tongue	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Oral dryness	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		1/8 (12.5%)
Paraesthesia lips	0/8 (0%)		2/8 (25%)		1/8 (12.5%)		0/8 (0%)
Paraesthesia tongue	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Vomiting	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
General disorders
Feeling hungry	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Tiredness	1/8 (12.5%)		6/8 (75%)		1/8 (12.5%)		2/8 (25%)
Infections and infestations
Vaginal infection	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Injury, poisoning and procedural complications
Accidental injury	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Leg pain	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Nervous system disorders
Acroparaesthesia	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Concentration loss	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Dizziness	2/8 (25%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Head pressure	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Headache	3/8 (37.5%)		3/8 (37.5%)		1/8 (12.5%)		1/8 (12.5%)
Psychiatric disorders
Increased libido	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Blister of fingers, without mention of infection	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Herpes labialis	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Itching	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Bulla dorsum manus	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)
Surgical and medical procedures
Tooth extraction	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.