Trial Outcomes & Findings for Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy (NCT NCT00957047)
NCT ID: NCT00957047
Last Updated: 2025-03-25
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 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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
395 participants
Primary outcome timeframe
12-week maintenance period
Results posted on
2025-03-25
Participant Flow
STUDY DATES: PART I - From: 01 Sep 2004 To: 19 Dec 2006; PART II - From: 02 February 2005 To: 29 January 2008 Patients were screened at 46 sites in 13 countries for Part I and Patients from 42 sites in 12 countries continued in part II.;
Part I was a 22-week parallel-group, randomized, placebo controlled period. After completing the baseline period, patients were randomized in a 1:1:1:1 ratio to 1 of the 3 ESL dose levels or to placebo. For Part I 400 patients were planned; of 503 patients screened, 395 were randomized. 325 patients who completed Part I were enrolled in Part II.
Participant milestones
| Measure |
Placebo
placebo : once daily placebo comparator
|
ESL 400 mg Once Daily
eslicarbazepine acetate : oral tablets
|
ESL 800 mg Once Daily
eslicarbazepine acetate : oral tablets
|
ESL 1200 mg Once Daily
eslicarbazepine acetate : oral tablets
|
ESL - Part II
All patients in Part II received ESL on an open-label basis, starting at 800 mg once daily.
|
|---|---|---|---|---|---|
|
PART I
STARTED
|
100
|
96
|
101
|
98
|
0
|
|
PART I
Randomized/Safety Population
|
100
|
96
|
101
|
98
|
0
|
|
PART I
Intention-to-treat (ITT) Population
|
100
|
96
|
100
|
97
|
0
|
|
PART I
Per-Protocol Population
|
81
|
70
|
75
|
54
|
0
|
|
PART I
COMPLETED
|
94
|
83
|
80
|
68
|
0
|
|
PART I
NOT COMPLETED
|
6
|
13
|
21
|
30
|
0
|
|
PART II
STARTED
|
0
|
0
|
0
|
0
|
325
|
|
PART II
Terminated Prematurely
|
0
|
0
|
0
|
0
|
102
|
|
PART II
COMPLETED
|
0
|
0
|
0
|
0
|
223
|
|
PART II
NOT COMPLETED
|
0
|
0
|
0
|
0
|
102
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy
Baseline characteristics by cohort
| Measure |
ESL 1200 mg Once Daily
n=98 Participants
eslicarbazepine acetate : oral tablets
|
ESL 400 mg Once Daily
n=96 Participants
eslicarbazepine acetate : oral tablets
|
ESL 800 mg Once Daily
n=101 Participants
eslicarbazepine acetate : oral tablets
|
Placebo
n=100 Participants
placebo : once daily placebo comparator
|
Total
n=395 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=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, Categorical
Between 18 and 65 years
|
98 Participants
n=5 Participants
|
96 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
98 Participants
n=4 Participants
|
393 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
201 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
52 Participants
n=4 Participants
|
194 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12-week maintenance periodPopulation: The primary efficacy analysis was an ANCOVA that assessed reduction in seizure frequency per 4 weeks for the ITT population during the 12-week maintenance period
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the 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.
Outcome measures
| Measure |
ESL 1200 mg Once Daily
n=97 Participants
eslicarbazepine acetate : oral tablets
|
ESL 400 mg Once Daily
n=96 Participants
eslicarbazepine acetate : oral tablets
|
ESL 800 mg Once Daily
n=100 Participants
eslicarbazepine acetate : oral tablets
|
Placebo
n=100 Participants
placebo : once daily placebo comparator
|
TEAE Leading to Discontinuation
|
Serious TEAE
|
TEAE Leading to Death
|
|---|---|---|---|---|---|---|---|
|
PART I - Seizure Frequency
|
7 ln (Seizures) per 4 weeks
Interval 6.0 to 8.1
|
8.7 ln (Seizures) per 4 weeks
Interval 7.7 to 9.9
|
7.1 ln (Seizures) per 4 weeks
Interval 6.2 to 8.2
|
9.8 ln (Seizures) per 4 weeks
Interval 8.7 to 11.1
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 1 yearSafety assessments were based primarily on AEs (Number of patients who experienced at least one AEs), and on whether these were related to the study medication, were serious, led to permanent discontinuation of study participation, or led to death.
Outcome measures
| Measure |
ESL 1200 mg Once Daily
n=325 Participants
eslicarbazepine acetate : oral tablets
|
ESL 400 mg Once Daily
n=325 Participants
eslicarbazepine acetate : oral tablets
|
ESL 800 mg Once Daily
n=325 Participants
eslicarbazepine acetate : oral tablets
|
Placebo
n=325 Participants
placebo : once daily placebo comparator
|
TEAE Leading to Discontinuation
n=325 Participants
|
Serious TEAE
n=325 Participants
|
TEAE Leading to Death
n=325 Participants
|
|---|---|---|---|---|---|---|---|
|
PART II - Nº of Treatment-Emergent Adverse Events (TEAE)
|
270 participants
|
151 participants
|
240 participants
|
194 participants
|
37 participants
|
28 participants
|
3 participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 59 other events
Deaths: 0 deaths
ESL 400 mg
Serious events: 4 serious events
Other events: 75 other events
Deaths: 0 deaths
ESL 800 mg
Serious events: 6 serious events
Other events: 84 other events
Deaths: 0 deaths
ESL 1200 mg
Serious events: 2 serious events
Other events: 78 other events
Deaths: 0 deaths
ESL PART II
Serious events: 28 serious events
Other events: 270 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=100 participants at risk
Tablets; oral route
|
ESL 400 mg
n=96 participants at risk
Tablets; oral route
|
ESL 800 mg
n=101 participants at risk
Tablets; oral route
|
ESL 1200 mg
n=98 participants at risk
Tablets; oral route
|
ESL PART II
n=325 participants at risk
All patients in Part II received ESL
|
|---|---|---|---|---|---|
|
Psychiatric disorders
Acute psychosis
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Psychiatric disorders
Aggression
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Gastrointestinal disorders
Appendix disorder
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
—
0/0
|
—
0/0
|
—
0/0
|
—
0/0
|
0.31%
1/325
|
|
General disorders
Asthenia
|
0.00%
0/100
|
—
0/0
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Convulsion
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.92%
3/325
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
2.0%
2/101 • Number of events 2
|
1.0%
1/98 • Number of events 1
|
0.31%
1/325
|
|
Psychiatric disorders
Depression
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
0.00%
0/98
|
0.00%
0/325
|
|
Eye disorders
Diplopia
|
0.00%
0/100
|
2.1%
2/96 • Number of events 2
|
0.00%
0/101
|
0.00%
0/98
|
0.00%
0/325
|
|
Nervous system disorders
Dizziness
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
1.0%
1/98 • Number of events 1
|
0.00%
0/325
|
|
General disorders
Drowning
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.31%
1/325
|
|
Gastrointestinal disorders
Dyskinesia oesophageal
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Reproductive system and breast disorders
Endometriosis
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.00%
0/325
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Follicle centre lymphoma, follicular grade I, II, III
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.00%
0/325
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
0.00%
0/98
|
0.00%
0/325
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Injury, poisoning and procedural complications
Hepatic rupture
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.00%
0/325
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Insulinoma
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/100
|
0.00%
0/96
|
—
0/0
|
0.00%
0/98
|
0.31%
1/325
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Investigations
Monocyte count decreased
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
0.00%
0/98
|
0.00%
0/325
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Reproductive system and breast disorders
Ovarian mass
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Infections and infestations
Pneumonia
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
0.00%
0/98
|
0.62%
2/325
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/100
|
0.00%
0/96
|
0.99%
1/101 • Number of events 1
|
0.00%
0/98
|
0.00%
0/325
|
|
Psychiatric disorders
Schizoaffective disorder
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Somnolence
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.62%
2/325
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.62%
2/325
|
|
General disorders
Sudden death
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
|
Nervous system disorders
Vasculitis cerebral
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
0.00%
0/101
|
0.00%
0/98
|
0.00%
0/325
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/100
|
1.0%
1/96 • Number of events 1
|
2.0%
2/101 • Number of events 2
|
1.0%
1/98 • Number of events 1
|
0.00%
0/325
|
|
Investigations
White blood cell count decreased
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
0.31%
1/325
|
Other adverse events
| Measure |
Placebo
n=100 participants at risk
Tablets; oral route
|
ESL 400 mg
n=96 participants at risk
Tablets; oral route
|
ESL 800 mg
n=101 participants at risk
Tablets; oral route
|
ESL 1200 mg
n=98 participants at risk
Tablets; oral route
|
ESL PART II
n=325 participants at risk
All patients in Part II received ESL
|
|---|---|---|---|---|---|
|
Nervous system disorders
Coordination abnormal
|
5.0%
5/100 • Number of events 5
|
5.2%
5/96 • Number of events 5
|
12.9%
13/101 • Number of events 13
|
11.2%
11/98 • Number of events 11
|
8.6%
28/325
|
|
Eye disorders
Diplopia
|
4.0%
4/100 • Number of events 4
|
8.3%
8/96 • Number of events 8
|
14.9%
15/101 • Number of events 15
|
10.2%
10/98 • Number of events 10
|
8.6%
28/325
|
|
Nervous system disorders
Dizziness
|
10.0%
10/100 • Number of events 10
|
22.9%
22/96 • Number of events 22
|
29.7%
30/101 • Number of events 30
|
43.9%
43/98 • Number of events 43
|
26.5%
86/325
|
|
General disorders
Fatigue
|
5.0%
5/100 • Number of events 5
|
4.2%
4/96 • Number of events 4
|
5.0%
5/101 • Number of events 5
|
7.1%
7/98 • Number of events 7
|
0.00%
0/325
|
|
Nervous system disorders
Headache
|
9.0%
9/100 • Number of events 9
|
12.5%
12/96 • Number of events 12
|
14.9%
15/101 • Number of events 15
|
19.4%
19/98 • Number of events 19
|
15.7%
51/325
|
|
Gastrointestinal disorders
Nausea
|
4.0%
4/100 • Number of events 4
|
8.3%
8/96 • Number of events 8
|
11.9%
12/101 • Number of events 12
|
15.3%
15/98 • Number of events 15
|
6.5%
21/325
|
|
Nervous system disorders
Somnolence
|
17.0%
17/100 • Number of events 17
|
15.6%
15/96 • Number of events 15
|
16.8%
17/101 • Number of events 17
|
21.4%
21/98 • Number of events 21
|
12.0%
39/325
|
|
Eye disorders
Vision blurred
|
2.0%
2/100 • Number of events 2
|
7.3%
7/96 • Number of events 7
|
7.9%
8/101 • Number of events 8
|
7.1%
7/98 • Number of events 7
|
5.2%
17/325
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
3/100 • Number of events 3
|
4.2%
4/96 • Number of events 4
|
12.9%
13/101 • Number of events 13
|
10.2%
10/98 • Number of events 10
|
6.8%
22/325
|
|
Investigations
Blood pressure diastolic decreased
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
8.6%
28/325
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
6.2%
20/325
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
5.5%
18/325
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/100
|
0.00%
0/96
|
0.00%
0/101
|
0.00%
0/98
|
5.2%
17/325
|
Additional Information
Head of Clinical Research Section
Bial - Portela & Cª, S.A.
Phone: + 351 22 986 61 00
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER