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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00957372
Recruitment Status : Completed
First Posted : August 12, 2009
Results First Posted : August 5, 2013
Last Update Posted : July 2, 2014
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Partial Epilepsy
Interventions Drug: eslicarbazepine acetate
Drug: placebo (Part I)
Drug: ESL - Open-label Extension (Part II)
Enrollment 253
Recruitment Details

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

Pre-assignment Details 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
Arm/Group Title ESL 1200mg Daily ESL 800mg Daily Placebo Open-label Extension (Part II)
Hide Arm/Group Description

ESL 1200mg daily

eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily

ESL 800mg daily

eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily

placebo

placebo : once daily placebo comparator

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.
Period Title: PART I
Started 80 85 88 0
Safety Population 80 85 87 0
Intention-to-Treat Population 77 84 84 0
Per-Protocol Population 35 47 51 0
Randomized But Not Treated 0 0 1 0
Completed 80 85 87 0
Not Completed 0 0 1 0
Reason Not Completed
Lost to Follow-up             0             0             1             0
Period Title: PART II
Started 0 0 0 194
Safety Population 0 0 0 194
Intention-to-treat (ITT) Population 0 0 0 191
Per-Protocol Population 0 0 0 108
Completed 0 0 0 150
Not Completed 0 0 0 44
Reason Not Completed
Withdrawal by Subject             0             0             0             8
Physician Decision             0             0             0             1
Pregnancy             0             0             0             1
Not Know             0             0             0             20
Adverse Event             0             0             0             10
Patient non-compliance             0             0             0             4
Arm/Group Title ESL 1200mg Daily ESL 800mg Daily Placebo Total
Hide Arm/Group Description

ESL 1200mg daily

eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily

ESL 800mg daily

eslicarbazepine acetate : oral tablet, 800 mg or 1200 mg once daily

placebo

placebo : once daily placebo comparator

Total of all reporting groups
Overall Number of Baseline Participants 80 85 88 253
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 80 participants 85 participants 88 participants 253 participants
<=18 years 2 2 2 6
Between 18 and 65 years 76 82 83 241
>=65 years 2 1 3 6
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 85 participants 88 participants 253 participants
Female
45
  56.3%
50
  58.8%
45
  51.1%
140
  55.3%
Male
35
  43.8%
35
  41.2%
43
  48.9%
113
  44.7%
1.Primary Outcome
Title Seizure Frequency
Hide Description 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
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo ESL 800 mg ESL 1200 mg
Hide Arm/Group Description:
Placebo tablets matching the 400 and 600 mg active substance tablets were supplied.
400 mg active substance tablets were supplied
400 and 600 mg active substance tablets were supplied
Overall Number of Participants Analyzed 84 84 77
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ln (Seizures) per 4 weeks
7.3
(6.3 to 8.5)
5.7
(4.9 to 6.7)
5.5
(4.6 to 6.5)
2.Primary Outcome
Title PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
Hide Description 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.
Time Frame 1-year
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TEAE TEAE With Onset Within the First 4 Weeks of Part II TEAE With Onset After the First 4 Weeks of Part II Treatment-related Treatment-emergent Adverse Event TEAE Leading to Discontinuation From the Study Treatment Emergent Serious Adverse Event TEAE Leading to Death
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 194 194 194 194 194 194 194
Measure Type: Number
Unit of Measure: participants
112 40 94 66 9 11 2
Time Frame Overall study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo ESL 800 mg ESL 1200 mg Open-label Extension (Part II)
Hide Arm/Group Description Placebo tablets matching the 400 and 600 mg active substance tablets were supplied 400 mg active substance tablets were supplied 400 and 600 mg active substance tablets were supplied 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.
All-Cause Mortality
Placebo ESL 800 mg ESL 1200 mg Open-label Extension (Part II)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo ESL 800 mg ESL 1200 mg Open-label Extension (Part II)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/87 (0.00%)      0/85 (0.00%)      1/80 (1.25%)      11/194 (5.67%)    
Hepatobiliary disorders         
SUSPECTED HEPATITIS  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Infections and infestations         
INFECTION URINARY HYPONATREMIA  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Injury, poisoning and procedural complications         
THIRD GRADE BURN ON RIGHT ARM  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
POLYTRAUMA  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
POST PROCEDURAL HEMATOMA DUE TO HYSTERECTOMY COMPLICATIONS  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
CRANIAL TRAUMA - POLYCONTUSION  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Musculoskeletal and connective tissue disorders         
RHEUMATOID NODULES  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
ASTROCYTOMA REFERS TO TUMORAL RELAPSE  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Nervous system disorders         
CEREBELLAR SYNDROME  1  0/87 (0.00%)  0 0/85 (0.00%)  0 1/80 (1.25%)  1 1/194 (0.52%)  1
EPILEPTIC STATUS  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
TRANSITORY ISQUEMIC ATTACK  1  0/87 (0.00%)  0 0/85 (0.00%)  0 0/80 (0.00%)  0 1/194 (0.52%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo ESL 800 mg ESL 1200 mg Open-label Extension (Part II)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/87 (35.63%)      41/85 (48.24%)      57/80 (71.25%)      80/194 (41.24%)    
Gastrointestinal disorders         
Nausea  1  1/87 (1.15%)  1 5/85 (5.88%)  5 8/80 (10.00%)  8 0/194 (0.00%)  0
Vomiting  1  3/87 (3.45%)  3 4/85 (4.71%)  4 6/80 (7.50%)  6 11/194 (5.67%)  11
Nervous system disorders         
Dizziness  1  9/87 (10.34%)  9 16/85 (18.82%)  16 24/80 (30.00%)  24 33/194 (17.01%)  33
Somnolence  1  8/87 (9.20%)  8 11/85 (12.94%)  11 11/80 (13.75%)  11 19/194 (9.79%)  19
Headache  1  10/87 (11.49%)  10 5/85 (5.88%)  5 8/80 (10.00%)  8 17/194 (8.76%)  17
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Clinical Research Section
Organization: Bial - Portela & Cª, S.A.
Phone: + 351 22 986 61 00
EMail: clinical.trials@bial.com
Layout table for additonal information
Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT00957372    
Other Study ID Numbers: BIA-2093-303
First Submitted: August 10, 2009
First Posted: August 12, 2009
Results First Submitted: March 26, 2013
Results First Posted: August 5, 2013
Last Update Posted: July 2, 2014