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

Phase 3

Completed

• Conditions: Epilepsy
• Interventions: Drug: Brivaracetam

• Registration Number: NCT01653262
• Lead Sponsor: UCB Pharma SA

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-26
• Study First Submitted QC: 2012-07-26
• Study First Posted: 2012-07-30
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Disposition First Submitted: 2013-12-20
• Disposition First Submitted QC: 2013-12-20
• Disposition First Posted: 2014-01-28
• Results First Submitted: 2016-03-14
• Status Verified: 2016-07
• Results First Submitted QC: 2016-07-05
• Results First Posted: 2016-08-15
• Last Update Submitted: 2018-06-13
• Last Update Posted: 2018-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Brivaracetam	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.

Primary Outcome Measures

Name	Time	Method
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	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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

Name	Time	Method
Incidence of Treatment Emergent Adverse Events During the Study Period	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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.
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	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	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.
Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy	From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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	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 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.
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	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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 Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period	From Visit 2 (Week 0) to Visit 6 (Week 12)	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.
Occurrence of Serious Adverse Events During the Study Period	From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit	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.
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	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	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.

Trial Locations

Locations (12)

108; 🇺🇸 Lexington, Kentucky, United States

103; 🇺🇸 Little Rock, Arkansas, United States

109; 🇺🇸 New York, New York, United States

106; 🇺🇸 Akron, Ohio, United States

110; 🇺🇸 Dallas, Texas, United States

102; 🇺🇸 Salt Lake City, Utah, United States

203; 🇫🇷 Amiens, France

303; 🇩🇪 Bernau, Germany

201; 🇫🇷 Paris, France

300; 🇩🇪 Kehl-Kork, Germany

502; 🇪🇸 Sevilla, Spain

603; 🇬🇧 Salford, United Kingdom