Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy (NCT NCT00957372)
NCT ID: NCT00957372
Last Updated: 2014-07-02
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 results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
253 participants
Primary outcome timeframe
12 weeks
Results posted on
2014-07-02
Participant Flow
Patients were screened at 39 sites in 3 countries. STUDY DATES: PART I: from: 14 Dec 2004 to: 19 Jan 2007 PART II: from 21 June 2005 to 22 January 2008
The duration of Part I was 26 weeks, including the 8-week baseline period. After completing the baseline period, patients were randomized in a 1:1:1 ratio to 1 of the 2 ESL daily dose levels (1200 or 800 mg) or placebo.Part II was a 1-year open-label extension for patients who had completed Part I
Participant milestones
| Measure |
ESL 1200mg Daily
ESL 1200mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
ESL 800mg Daily
ESL 800mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
Placebo
placebo
placebo : once daily placebo comparator
|
Open-label Extension (Part II)
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
|---|---|---|---|---|
|
PART I
STARTED
|
80
|
85
|
88
|
0
|
|
PART I
Safety Population
|
80
|
85
|
87
|
0
|
|
PART I
Intention-to-Treat Population
|
77
|
84
|
84
|
0
|
|
PART I
Per-Protocol Population
|
35
|
47
|
51
|
0
|
|
PART I
Randomized But Not Treated
|
0
|
0
|
1
|
0
|
|
PART I
COMPLETED
|
80
|
85
|
87
|
0
|
|
PART I
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
PART II
STARTED
|
0
|
0
|
0
|
194
|
|
PART II
Safety Population
|
0
|
0
|
0
|
194
|
|
PART II
Intention-to-treat (ITT) Population
|
0
|
0
|
0
|
191
|
|
PART II
Per-Protocol Population
|
0
|
0
|
0
|
108
|
|
PART II
COMPLETED
|
0
|
0
|
0
|
150
|
|
PART II
NOT COMPLETED
|
0
|
0
|
0
|
44
|
Reasons for withdrawal
| Measure |
ESL 1200mg Daily
ESL 1200mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
ESL 800mg Daily
ESL 800mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
Placebo
placebo
placebo : once daily placebo comparator
|
Open-label Extension (Part II)
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
|---|---|---|---|---|
|
PART I
Lost to Follow-up
|
0
|
0
|
1
|
0
|
|
PART II
Withdrawal by Subject
|
0
|
0
|
0
|
8
|
|
PART II
Physician Decision
|
0
|
0
|
0
|
1
|
|
PART II
Pregnancy
|
0
|
0
|
0
|
1
|
|
PART II
Not Know
|
0
|
0
|
0
|
20
|
|
PART II
Adverse Event
|
0
|
0
|
0
|
10
|
|
PART II
Patient non-compliance
|
0
|
0
|
0
|
4
|
Baseline Characteristics
Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy
Baseline characteristics by cohort
| Measure |
ESL 1200mg Daily
n=80 Participants
ESL 1200mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
ESL 800mg Daily
n=85 Participants
ESL 800mg daily
eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily
|
Placebo
n=88 Participants
placebo
placebo : once daily placebo comparator
|
Total
n=253 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<=18 years
|
2 participants
n=99 Participants
|
2 participants
n=107 Participants
|
2 participants
n=206 Participants
|
6 participants
n=7 Participants
|
|
Age, Customized
Between 18 and 65 years
|
76 participants
n=99 Participants
|
82 participants
n=107 Participants
|
83 participants
n=206 Participants
|
241 participants
n=7 Participants
|
|
Age, Customized
>=65 years
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
6 participants
n=7 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
140 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
113 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: The primary efficacy analysis was based on the ITT population.The intent-to-treat (ITT) population included all randomized patients with at least one dose of investigational product and at least one post-baseline seizure frequency assessment
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate
Outcome measures
| Measure |
Placebo
n=84 Participants
Placebo tablets matching the 400 and 600 mg active substance tablets were supplied.
|
ESL 800 mg
n=84 Participants
400 mg active substance tablets were supplied
|
ESL 1200 mg
n=77 Participants
400 and 600 mg active substance tablets were supplied
|
Treatment-related Treatment-emergent Adverse Event
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
TEAE Leading to Discontinuation From the Study
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
Treatment Emergent Serious Adverse Event
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
TEAE Leading to Death
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
|---|---|---|---|---|---|---|---|
|
Seizure Frequency
|
7.3 ln (Seizures) per 4 weeks
Interval 6.3 to 8.5
|
5.7 ln (Seizures) per 4 weeks
Interval 4.9 to 6.7
|
5.5 ln (Seizures) per 4 weeks
Interval 4.6 to 6.5
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 1-yearPopulation: There was no sample size estimate for Part II. Part II was a 1-year open-label extension for patients who had completed Part I and was willing to continue treatment in Part II.
The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality.
Outcome measures
| Measure |
Placebo
n=194 Participants
Placebo tablets matching the 400 and 600 mg active substance tablets were supplied.
|
ESL 800 mg
n=194 Participants
400 mg active substance tablets were supplied
|
ESL 1200 mg
n=194 Participants
400 and 600 mg active substance tablets were supplied
|
Treatment-related Treatment-emergent Adverse Event
n=194 Participants
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
TEAE Leading to Discontinuation From the Study
n=194 Participants
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
Treatment Emergent Serious Adverse Event
n=194 Participants
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
TEAE Leading to Death
n=194 Participants
Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day.
|
|---|---|---|---|---|---|---|---|
|
PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
|
112 participants
|
40 participants
|
94 participants
|
66 participants
|
9 participants
|
11 participants
|
2 participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths
ESL 800 mg
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
ESL 1200 mg
Serious events: 1 serious events
Other events: 57 other events
Deaths: 0 deaths
Open-label Extension (Part II)
Serious events: 11 serious events
Other events: 80 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=87 participants at risk
Placebo tablets matching the 400 and 600 mg active substance tablets were supplied
|
ESL 800 mg
n=85 participants at risk
400 mg active substance tablets were supplied
|
ESL 1200 mg
n=80 participants at risk
400 and 600 mg active substance tablets were supplied
|
Open-label Extension (Part II)
n=194 participants at risk
ESL dose taken; Starting at 800 mg once daily, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg once daily or up to a maximum of 1200 mg once daily.
|
|---|---|---|---|---|
|
Nervous system disorders
CEREBELLAR SYNDROME
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
1.2%
1/80 • Number of events 1 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID NODULES
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Hepatobiliary disorders
SUSPECTED HEPATITIS
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Infections and infestations
INFECTION URINARY HYPONATREMIA
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ASTROCYTOMA REFERS TO TUMORAL RELAPSE
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Injury, poisoning and procedural complications
THIRD GRADE BURN ON RIGHT ARM
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Nervous system disorders
EPILEPTIC STATUS
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Injury, poisoning and procedural complications
POLYTRAUMA
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL HEMATOMA DUE TO HYSTERECTOMY COMPLICATIONS
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Injury, poisoning and procedural complications
CRANIAL TRAUMA - POLYCONTUSION
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
|
Nervous system disorders
TRANSITORY ISQUEMIC ATTACK
|
0.00%
0/87 • Overall study
|
0.00%
0/85 • Overall study
|
0.00%
0/80 • Overall study
|
0.52%
1/194 • Number of events 1 • Overall study
|
Other adverse events
| Measure |
Placebo
n=87 participants at risk
Placebo tablets matching the 400 and 600 mg active substance tablets were supplied
|
ESL 800 mg
n=85 participants at risk
400 mg active substance tablets were supplied
|
ESL 1200 mg
n=80 participants at risk
400 and 600 mg active substance tablets were supplied
|
Open-label Extension (Part II)
n=194 participants at risk
ESL dose taken; Starting at 800 mg once daily, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg once daily or up to a maximum of 1200 mg once daily.
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
10.3%
9/87 • Number of events 9 • Overall study
|
18.8%
16/85 • Number of events 16 • Overall study
|
30.0%
24/80 • Number of events 24 • Overall study
|
17.0%
33/194 • Number of events 33 • Overall study
|
|
Nervous system disorders
Somnolence
|
9.2%
8/87 • Number of events 8 • Overall study
|
12.9%
11/85 • Number of events 11 • Overall study
|
13.8%
11/80 • Number of events 11 • Overall study
|
9.8%
19/194 • Number of events 19 • Overall study
|
|
Nervous system disorders
Headache
|
11.5%
10/87 • Number of events 10 • Overall study
|
5.9%
5/85 • Number of events 5 • Overall study
|
10.0%
8/80 • Number of events 8 • Overall study
|
8.8%
17/194 • Number of events 17 • Overall study
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/87 • Number of events 1 • Overall study
|
5.9%
5/85 • Number of events 5 • Overall study
|
10.0%
8/80 • Number of events 8 • Overall study
|
0.00%
0/194 • Overall study
|
|
Gastrointestinal disorders
Vomiting
|
3.4%
3/87 • Number of events 3 • Overall study
|
4.7%
4/85 • Number of events 4 • Overall study
|
7.5%
6/80 • Number of events 6 • Overall study
|
5.7%
11/194 • Number of events 11 • Overall study
|
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