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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Brivaracetam

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • 203
  • Paris, France
    • 201
• Germany
  • Bernau, Germany
    • 303
  • Kehl-Kork, Germany
    • 300
• Spain
  • Sevilla, Spain
    • 502
• United Kingdom
  • Salford, United Kingdom
    • 603
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
      • 103
  • Kentucky
    • Lexington, Kentucky, United States
      • 108
  • New York
    • New York, New York, United States
      • 109
  • Ohio
    • Akron, Ohio, United States
      • 106
  • Texas
    • Dallas, Texas, United States
      • 110
  • Utah
    • Salt Lake City, Utah, United States
      • 102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Drug: Brivaracetam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
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.	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
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.	From Visit 2 (Week 0) to Visit 6 (Week 12)
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.	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
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.	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
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.	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
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)	From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
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.	From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit

Collaborators and Investigators

• Sponsor: UCB Pharma SA

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: July 26, 2012
• First Submitted That Met QC Criteria: July 26, 2012
• First Posted (Estimate): July 30, 2012

Study Record Updates

• Last Update Posted (Actual): July 11, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Epilepsy; Brivaracetam; Levetiracetam; Nonpsychotic behavior
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Anticonvulsants; Brivaracetam
• Other Study ID Numbers: N01395; 2011-005177-23 (EudraCT Number)