Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier:
NCT01653262
First received: July 26, 2012
Last updated: July 5, 2016
Last verified: July 2016

July 26, 2012
July 5, 2016
July 2012
November 2013   (final data collection date for primary outcome measure)
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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]

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

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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01653262 on ClinicalTrials.gov Archive Site
  • 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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]

    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Visit 2 (Week 0) to Visit 6 (Week 12) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]

    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 [ 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 ] [ Designated as safety issue: No ]

    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.

  • 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 [ 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]

    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 [ 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 ] [ Designated as safety issue: No ]
  • Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period [ Time Frame: From Visit 2 (Week 0) to Visit 6 (Week 12) ] [ Designated as safety issue: No ]
  • Incidence of Treatment Emergent Adverse Events During the Study Period [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
  • Withdrawal Due to an Adverse Event (AE) During the Study Period [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
  • Occurrence of Serious Adverse Events During the Study Period [ Time Frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit ] [ Designated as safety issue: No ]
  • Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy [ 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 ] [ Designated as safety issue: No ]
    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).
  • Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy [ 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 ] [ Designated as safety issue: No ]
    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).
Not Provided
Not Provided
 
Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)
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
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.
Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Epilepsy
Drug: Brivaracetam
Experimental: Brivaracetam

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: Drug: Brivaracetam
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
November 2013
November 2013   (final data collection date for primary outcome measure)

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
Both
16 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France,   Germany,   Spain,   United Kingdom
Italy
 
NCT01653262
N01395, 2011-005177-23
No
Not Provided
Not Provided
UCB Pharma SA
UCB Pharma SA
Not Provided
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
UCB Pharma
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP