Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures (NCT NCT00957684)

Last Updated: 2025-03-12

Results Overview

The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the intention-to-treat (ITT) population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.to a "frequency per 4 weeks" basis

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

402 participants

Primary outcome timeframe

12-week maintenance period

Results posted on

2025-03-12

Participant Flow

Study initiation date: 15/July/2004(first visit of the first patient) Study Part I completion date: 09/November/2005(last Part I visit of the last patient) Study Part II initiation date: 11 JAN 2005 (first Part II visit of the first patient) Study Part II completion date: 04 JAN 2007 (last Part II visit of the last patient)

After completing the baseline period, patients were randomised in a 1:1:1:1 ratio to 1 of the 3 Eslicarbazepine acetate (ESL) dose levels or to placebo. Part II was a 1-year open-label extension for patients who had completed Part I

Participant milestones

Participant milestones
Measure	ESL 1200 mg Once Daily eslicarbazepine acetate : once-daily oral tablet	ESL 800 mg Once Daily eslicarbazepine acetate : once-daily oral tablet	ESL 400 mg Once Daily eslicarbazepine acetate : once-daily oral tablet	Placebo placebo : once daily placebo comparator	ESL - Part II During Part II of the study all patients received ESL, including those who had been treated with placebo during Part I. The duration of treatment during Part II was one year for all patients completing the study.
PART I STARTED	102	98	100	102	0
PART I Randomised (Safety Population)	102	98	100	102	0
PART I Intention-to-treat (ITT) Population	98	98	99	102	0
PART I Per-protocol (PP)Population	72	86	94	91	0
PART I COMPLETED	71	85	90	84	0
PART I NOT COMPLETED	31	13	10	18	0
PART II STARTED	0	0	0	0	314
PART II Patients Entered Part II	0	0	0	0	314
PART II COMPLETED	0	0	0	0	239
PART II NOT COMPLETED	0	0	0	0	75

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ESL 1200 mg n=102 Participants 400-mg + 800-mg; once daily administration by oral route	ESL 800 mg n=98 Participants 800-mg; once daily administration by oral route	ESL 400 mg n=100 Participants 400-mg; once daily administration by oral route	Placebo n=102 Participants Placebo tablets; once daily administration by oral route	Total n=402 Participants Total of all reporting groups
Age, Customized <=18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Age, Customized Between 18 and 70 years	102 participants n=5 Participants	96 participants n=7 Participants	99 participants n=5 Participants	102 participants n=4 Participants	399 participants n=21 Participants
Age, Customized >70 years	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	44 Participants n=7 Participants	49 Participants n=5 Participants	54 Participants n=4 Participants	204 Participants n=21 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	54 Participants n=7 Participants	51 Participants n=5 Participants	48 Participants n=4 Participants	198 Participants n=21 Participants

PRIMARY outcome

Timeframe: 12-week maintenance period

Population: The primary efficacy analysis was based on the ITT population.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Placebo tablets matching the 400-mg and 800-mg active substance tablets were supplied; once daily administration by oral route.	ESL 400 mg n=99 Participants ESL was supplied in 400-mg tablets; once daily administration by oral route.	ESL 800 mg n=98 Participants ESL was supplied in 800-mg tablets; once daily administration by oral route.	ESL 1200 mg n=98 Participants ESL was supplied in 400-mg and 800-mg tablets; once daily administration by oral route.
Part I: Seizure Frequency	7.64 ln (Seizures) per 4 weeks 95% Confidence Interval 0.0563 • Interval 6.78 to 8.58	6.73 ln (Seizures) per 4 weeks 95% Confidence Interval 0.0563 • Interval 5.93 to 7.6	5.66 ln (Seizures) per 4 weeks 95% Confidence Interval 0.0558 • Interval 4.92 to 6.45	5.35 ln (Seizures) per 4 weeks Interval 4.63 to 6.12

Adverse Events

ESL 1200 mg Once Daily

Serious events: 3 serious events

Other events: 62 other events

Deaths: 0 deaths

ESL 400 mg Once Daily

Serious events: 9 serious events

Other events: 27 other events

Deaths: 0 deaths

ESL 800 mg Once Daily

Serious events: 4 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ESL 1200 mg Once Daily n=102 participants at risk eslicarbazepine acetate : once-daily oral tablet	ESL 400 mg Once Daily n=100 participants at risk eslicarbazepine acetate : once-daily oral tablet	ESL 800 mg Once Daily n=98 participants at risk eslicarbazepine acetate : once-daily oral tablet	Placebo n=102 participants at risk placebo : once daily placebo comparator
Nervous system disorders Dizziness	13.7% 14/102 • Number of events 14 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	4.0% 4/100 • Number of events 4 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	14.3% 14/98 • Number of events 14 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/102 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Nervous system disorders Headache	10.8% 11/102 • Number of events 11 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	5.0% 5/100 • Number of events 5 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	9.2% 9/98 • Number of events 9 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	5.9% 6/102 • Number of events 6 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Nervous system disorders Somnolence	9.8% 10/102 • Number of events 10 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	6.0% 6/100 • Number of events 6 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	9.2% 9/98 • Number of events 9 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/102 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Eye disorders Diplopia	10.8% 11/102 • Number of events 11 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/100 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	7.1% 7/98 • Number of events 7 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	0.00% 0/102 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Gastrointestinal disorders Nausea	4.9% 5/102 • Number of events 5 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/100 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	4.1% 4/98 • Number of events 4 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	0.98% 1/102 • Number of events 1 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Ear and labyrinth disorders Vertigo	5.9% 6/102 • Number of events 6 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/100 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/98 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	0.98% 1/102 • Number of events 1 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Infections and infestations Influenza	3.9% 4/102 • Number of events 4 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	3.0% 3/100 • Number of events 3 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	4.1% 4/98 • Number of events 4 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	0.00% 0/102 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).
Nervous system disorders Complex partial seizures	2.9% 3/102 • Number of events 3 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	3.0% 3/100 • Number of events 3 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	1.0% 1/98 • Number of events 1 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).	2.0% 2/102 • Number of events 2 • 26-week Safety endpoints included Adverse events (AEs), clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram, and blood trough levels of concomitant Anti-epileptic drug (AEDs).

Additional Information

Head of Clinical Research Section

BIAL - Portela & Ca, SA

Phone: 351 22 986 6100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER