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Trial record 1 of 1 for:    NCT01653262
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Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)

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ClinicalTrials.gov Identifier: NCT01653262
Recruitment Status : Completed
First Posted : July 30, 2012
Results First Posted : August 15, 2016
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Drug: Brivaracetam
Enrollment 29
Recruitment Details This study started to enroll subjects in July 2012. In Oct 2013, the Sponsor evaluated the study in light of the recruitment rate. Given the unanticipated lack of recruitment during the prior 8 weeks, a decision was made to stop recruitment as of 16 Oct 2013.
Pre-assignment Details Participant Flow refers to the Enrolled Set. In total, 32 subjects were screened and 29 subjects were enrolled instead of 30 subjects as per protocol amendment 2. This difference was considered as insignificant and not affecting the planned analysis.
Arm/Group Title Brivaracetam
Hide Arm/Group Description

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Period Title: Overall Study
Started 29
Completed 26
Not Completed 3
Reason Not Completed
Lack of Efficacy             1
SAE, non-fatal             1
AE, non-serious non-fatal             1
Arm/Group Title Brivaracetam
Hide Arm/Group Description

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Baseline Participants 29
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Enrolled Set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
<=18 years
0
   0.0%
Between 18 and 65 years
29
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants
35.8  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants
Female
14
  48.3%
Male
15
  51.7%
1.Primary Outcome
Title Percentage of Subjects Who Achieved a Clinically Meaningful Reduction of Nonpsychotic Behavioral Side Effects Based on the Investigator's Overall Assessment From Study Entry to the End of the Treatment Period
Hide Description

Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.

The Investigator completed the assessment by answering the following:

"Has there been a clinically meaningful reduction of nonpsychotic behavioral side effects since the start of BRV?"

- Yes/No

Time Frame From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline evaluation of behavioral side effects.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: percentage of subjects
93.1
2.Secondary Outcome
Title Shift in the Maximum Intensity From Baseline to the End of the Treatment Period for Side Effects Primarily Associated With Discontinuation of Levetiracetam (LEV) as Determined by the Investigator
Hide Description Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Time Frame From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline evaluation of behavioral side effects.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: subjects
Improvement 8
Unchanged 2
Worsening 0
Resolved 19
3.Secondary Outcome
Title Change From Study Entry in Nonpsychotic Behavioral Side Effects to the End of the Treatment Period/Early Discontinuation Visit, Measured by Means of the Investigator Global Evaluation of Nonpsychotic Behavioral Side Effects (I-GEBSE) Scale
Hide Description

There are seven levels for the I-GEBSE:

  • Marked improvement
  • Moderate improvement
  • Slight improvement
  • No change
  • Slight worsening
  • Moderate worsening
  • Marked worsening
Time Frame From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline evaluation of behavioral side effects.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: subjects
Marked improvement 10
Moderate improvement 10
Slight improvement 4
No change 2
Slight worsening 1
Moderate worsening 0
Marked worsening 1
Missing 1
4.Secondary Outcome
Title Number of Subjects Who Have a Complete Abatement of Nonpsychotic Behavioral Side Effects for the Last Assessment During the Treatment Period, Based on the Investigator's Overall Assessment
Hide Description Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Time Frame From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline evaluation of behavioral side effects.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: subjects
18
5.Secondary Outcome
Title Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period
Hide Description Nonpsychotic behavioral side effects (NBSE) include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Time Frame From Visit 2 (Week 0) to Visit 6 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline evaluation of behavioral side effects.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: subjects
3
6.Secondary Outcome
Title Incidence of Treatment Emergent Adverse Events During the Study Period
Hide Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment emergent AE is any event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.
Time Frame From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all subjects who received at least 1 dose of Brivaracetam.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: events
67
7.Secondary Outcome
Title Withdrawal Due to an Adverse Event (AE) During the Study Period
Hide Description An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time Frame From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all subjects who received at least 1 dose of Brivaracetam.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: subjects
2
8.Secondary Outcome
Title Occurrence of Serious Adverse Events During the Study Period
Hide Description A serious adverse event is any untoward medical occurrences in a subject administered study treatment, whether or not the event is related to treatment, with at least one of the follow outcomes: death, life-threatening, initial inpatient hospitalization or prolongation of hospitalization, significant or persistent disability/incapacity, congenital anomaly/birth defect, or an important medical event that may jeopardize the subject and require a medical/surgical intervention.
Time Frame From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all subjects who received at least 1 dose of Brivaracetam.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: events
1
9.Secondary Outcome
Title Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy
Hide Description

The POS frequency is standardized to a 28-day duration and changes in POS frequency are measured relative to the reported seizure counts for the 4 weeks prior to Visit 2 (Week 0).

Partial seizures can be classified into one of the following three groups:

  • Simple partial seizures (IA)
  • Complex partial seizures (IB)
  • Partial seizures evolving to secondarily generalized seizures (IC)
Time Frame From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set (EAS) consisted of all subjects who received at least 1 dose of Brivaracetam and had at least 1 post-Baseline day of seizure daily record card (subject diary card).
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 15
Median (Inter-Quartile Range)
Unit of Measure: partial onset seizures
6.0
(2.2 to 17.7)
10.Secondary Outcome
Title Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy
Hide Description

Generalized seizure days are standardized to a 28-day duration and changes in generalized seizure days are measured relative to the reported seizure counts for the 4 weeks prior to Visit 2 (Week 0).

Generalized seizures (Type II) include the following seizure types:

  • Absence (IIA1)
  • Atypical absence (IIA2)
  • Myoclonic (IIB)
  • Clonic (IIC)
  • Tonic (IID)
  • Tonic-clonic (IIE)
  • Atonic (IIF)

A specific effect of BRV on the occurrence of generalized seizures was not assessed.

Time Frame From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Hide Outcome Measure Data
Hide Analysis Population Description
This variable was not analyzed and no results are available.
Arm/Group Title Brivaracetam
Hide Arm/Group Description:

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse Events were collected from Screening Period (Week -1) over the 12-weeks Treatment Period until the Safety Visit (Week 15-18 + max 7 days).
Adverse Event Reporting Description Adverse Events refer to the Safety Set (SS) consisting of all subjects who received at least 1 dose of Brivaracetam.
 
Arm/Group Title Brivaracetam
Hide Arm/Group Description

The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.

Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.

At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks.

All-Cause Mortality
Brivaracetam
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Brivaracetam
Affected / at Risk (%) # Events
Total   1/29 (3.45%)    
Psychiatric disorders   
Suicidal ideation * 1  1/29 (3.45%)  1
Suicide attempt * 1  1/29 (3.45%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brivaracetam
Affected / at Risk (%) # Events
Total   13/29 (44.83%)    
General disorders   
Fatigue * 1  3/29 (10.34%)  3
Infections and infestations   
Nasopharyngitis * 1  2/29 (6.90%)  2
Musculoskeletal and connective tissue disorders   
Back pain * 1  3/29 (10.34%)  4
Nervous system disorders   
Headache * 1  5/29 (17.24%)  7
Dizziness * 1  2/29 (6.90%)  2
Tremor * 1  2/29 (6.90%)  2
Psychiatric disorders   
Depression * 1  2/29 (6.90%)  2
Insomnia * 1  2/29 (6.90%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA15.0
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: UCB (Study Director)
Organization: UCB Clinical Trial Call Center
Phone: +1 887 822 9493
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT01653262    
Other Study ID Numbers: N01395
2011-005177-23 ( EudraCT Number )
First Submitted: July 26, 2012
First Posted: July 30, 2012
Results First Submitted: March 14, 2016
Results First Posted: August 15, 2016
Last Update Posted: July 11, 2018