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Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)

Primary Purpose

Epilepsy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Brivaracetam
Sponsored by
UCB Pharma SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Brivaracetam, Levetiracetam, Epilepsy, Nonpsychotic behavior

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject with well-characterized Epilepsy according to the 1989 International League Against Epilepsy (ILAE) classification
  • Subject with Epilepsy who the investigator expects will benefit from Levetiracetam (LEV) but for whom the investigator has decided to discontinue due to nonpsychotic behavioral side effects following the introduction of LEV
  • Subject is currently receiving LEV at the recommended therapeutic dose (dose ranging from 1 g/day to 3 g/day)
  • Subject currently treated with minimum 2 and maximum 3 Anti-Epileptic Drugs (AEDs) including LEV. Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
  • Female subjects without childbearing potential (postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method

Exclusion Criteria:

  • Subject has a lifetime history of suicide attempt (including an actual, interrupted or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1
  • Subject whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries)
  • Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline
  • Subject has history or presence of known psychogenic nonepileptic seizures
  • Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment) which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
  • Subject is pregnant or lactating

Sites / Locations

  • 103
  • 108
  • 109
  • 106
  • 110
  • 102
  • 203
  • 201
  • 303
  • 300
  • 502
  • 603

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brivaracetam

Arm 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.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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
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.
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
There are seven levels for the I-GEBSE: Marked improvement Moderate improvement Slight improvement No change Slight worsening Moderate worsening Marked worsening
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
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.
Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period
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.
Incidence of Treatment Emergent Adverse Events During the Study Period
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.
Withdrawal Due to an Adverse Event (AE) During the Study Period
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.
Occurrence of Serious Adverse Events During the Study Period
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.
Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy
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)
Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy
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.

Full Information

First Posted
July 26, 2012
Last Updated
June 13, 2018
Sponsor
UCB Pharma SA
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1. Study Identification

Unique Protocol Identification Number
NCT01653262
Brief Title
Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)
Official Title
An Open-label, Multicenter, Single-arm Study to Evaluate the Reduction in Nonpsychotic Behavioral Side Effects in Subjects With Epilepsy Switching From Levetiracetam to Brivaracetam Due to Nonpsychotic Behavioral Side Effects Phase 3b
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Pharma SA

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Trial N01395 is to evaluate the reduction of nonpsychotic behavioral side effects in subjects with Epilepsy who switched to BRV 200 mg/day after discontinuing LEV due to such side effects; as well as the efficacy, safety and tolerability of BRV. No statistical hypothesis testing will be performed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Brivaracetam, Levetiracetam, Epilepsy, Nonpsychotic behavior

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brivaracetam
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Brivaracetam
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
Title
Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period
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)
Title
Incidence of Treatment Emergent Adverse Events During the Study Period
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
Title
Withdrawal Due to an Adverse Event (AE) During the Study Period
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
Title
Occurrence of Serious Adverse Events During the Study Period
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
Title
Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy
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
Title
Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject with well-characterized Epilepsy according to the 1989 International League Against Epilepsy (ILAE) classification Subject with Epilepsy who the investigator expects will benefit from Levetiracetam (LEV) but for whom the investigator has decided to discontinue due to nonpsychotic behavioral side effects following the introduction of LEV Subject is currently receiving LEV at the recommended therapeutic dose (dose ranging from 1 g/day to 3 g/day) Subject currently treated with minimum 2 and maximum 3 Anti-Epileptic Drugs (AEDs) including LEV. Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED Female subjects without childbearing potential (postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method Exclusion Criteria: Subject has a lifetime history of suicide attempt (including an actual, interrupted or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1 Subject whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries) Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline Subject has history or presence of known psychogenic nonepileptic seizures Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment) which impair reliable participation in the study or necessitate the use of medication not allowed by protocol Subject is pregnant or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
+1 877 822 9493 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
103
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
108
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
109
City
New York
State/Province
New York
Country
United States
Facility Name
106
City
Akron
State/Province
Ohio
Country
United States
Facility Name
110
City
Dallas
State/Province
Texas
Country
United States
Facility Name
102
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
203
City
Amiens
Country
France
Facility Name
201
City
Paris
Country
France
Facility Name
303
City
Bernau
Country
Germany
Facility Name
300
City
Kehl-Kork
Country
Germany
Facility Name
502
City
Sevilla
Country
Spain
Facility Name
603
City
Salford
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26432008
Citation
Yates SL, Fakhoury T, Liang W, Eckhardt K, Borghs S, D'Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015 Nov;52(Pt A):165-8. doi: 10.1016/j.yebeh.2015.09.005. Epub 2015 Sep 29.
Results Reference
derived

Learn more about this trial

Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)

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