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

Purpose

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.

Condition	Intervention	Phase
Epilepsy	Drug: Brivaracetam	Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy

Drug Information available for: Levetiracetam

U.S. FDA Resources

Further study details as provided by UCB, Inc.:

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 [ 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 ]

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 [ 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).

Estimated Enrollment:	100
Study Start Date:	July 2012
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653262

Contacts

Contact: UCB Clinical Trial Call Center

+1 877 822 9493

Hide Study Locations

Locations

United States, Arizona
107	Recruiting
Phoenix, Arizona, United States
United States, Arkansas
103	Recruiting
Little Rock, Arkansas, United States
United States, Florida
101	Recruiting
Tampa, Florida, United States
United States, Kentucky
108	Recruiting
Lexington, Kentucky, United States
United States, Maryland
105	Recruiting
Bethesda, Maryland, United States
United States, Minnesota
104	Recruiting
St. Paul, Minnesota, United States
United States, New York
109	Recruiting
New York, New York, United States
United States, Ohio
106	Recruiting
Akron, Ohio, United States
United States, Texas
110	Recruiting
Dallas, Texas, United States
United States, Utah
102	Recruiting
Salt Lake City, Utah, United States
France
203	Recruiting
Amiens, France
200	Recruiting
Bethune, France
202	Recruiting
Lille Cedex, France
201	Recruiting
Paris, France
Germany
304	Recruiting
Berlin, Germany
303	Recruiting
Bernau, Germany
301	Recruiting
Bielefeld, Germany
305	Recruiting
Bonn, Germany
302	Recruiting
Erlangen, Germany
300	Recruiting
Kehl-Kork, Germany
Italy
401	Recruiting
Arezzo, Italy
402	Recruiting
Roma, Italy
403	Recruiting
Roma, Italy
400	Recruiting
Troina, Italy
Spain
500	Recruiting
Madrid, Spain
503	Recruiting
Palma de Mallorca, Spain
502	Recruiting
Sevilla, Spain
United Kingdom
601	Recruiting
London, United Kingdom
603	Recruiting
Salford, United Kingdom
602	Recruiting
Sheffield, United Kingdom
600	Recruiting
Staffordshire, United Kingdom

Sponsors and Collaborators

UCB Pharma SA

Investigators

Study Director:

UCB Clinical Trial Call Center

+1 877 822 9493 (UCB)

More Information

No publications provided

Responsible Party:	UCB, Inc. ( UCB Pharma SA )
ClinicalTrials.gov Identifier:	NCT01653262 History of Changes
Other Study ID Numbers:	N01395, 2011-005177-23
Study First Received:	July 26, 2012
Last Updated:	April 22, 2013
Health Authority:	United States: Food and Drug Administration France: Agence Nationale de Sécurité du Médicament et des produits de santé Germany: Federal Institute for Drugs and Medical Devices Italy: The Italian Medicines Agency Spain: Spanish Agency of Medicines United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by UCB, Inc.:

Brivaracetam
Levetiracetam
Epilepsy
Nonpsychotic behavior

Additional relevant MeSH terms:

Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Etiracetam

Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Nootropic Agents

ClinicalTrials.gov processed this record on June 18, 2013