Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease in Adolescents and Adults - Full Text View

Purpose

The study will compare the efficacy and safety of brivaracetam with placebo in patients with Unverricht-Lundborg disease.

Condition	Intervention	Phase
Unverricht-Lundborg Disease	Drug: Brivaracetam 25 mg Drug: Brivaracetam 50 mg Other: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Study to Evaluate the Efficacy and Safety of Brivaracetam Used as Adjunctive Treatment for 12 Weeks in Adolescent and Adult Patients (≥16 Years) With Genetically Ascertained Unverricht-Lundborg Disease

Resource links provided by NLM:

Genetics Home Reference related topics: PRICKLE1-related progressive myoclonus epilepsy with ataxia Unverricht-Lundborg disease pyridoxal 5'-phosphate-dependent epilepsy

Drug Information available for: Brivaracetam

Genetic and Rare Diseases Information Center resources: Myoclonus Epilepsy Progressive Myoclonic Epilepsy Unverricht-Lundborg Disease

U.S. FDA Resources

Further study details as provided by UCB Pharma:

Primary Outcome Measures:

Percent reduction from baseline on the Action Myoclonus score (Unified Myoclonus Rating Scale (UMRS) Section 4) at the end of the Treatment Period [ Time Frame: End of treatment period (Week 14 or early discontinuation visit) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent reduction from baseline on the functional disability score (UMRS Section 5) at the end of the Treatment Period [ Time Frame: End of treatment period (week 14 or early discontinuation visit) ] [ Designated as safety issue: No ]
Percent reduction from baseline on the stimulus sensitivity score (UMRS Section 3) at the end of the Treatment Period [ Time Frame: End of treatment period (week 14 or early discontinuation visit) ] [ Designated as safety issue: No ]
Percent reduction from baseline on the myoclonus patient questionnaire (UMRS Section 1) at the end of the Treatment Period [ Time Frame: End of treatment period (week 14 or early discontinuation visit) ] [ Designated as safety issue: No ]
Global Evaluation Scale by Investigator (I-GES) at the end of the Treatment Period [ Time Frame: End of treatment period (week 14 or early discontinuation visit) ] [ Designated as safety issue: No ]


Enrollment:	50
Study Start Date:	November 2006
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo	Other: Placebo Active Substance: Placebo Pharmaceutical Form: Tablet Concentration: 25 mg and 50 mg Route of Administration: Oral use
Experimental: Brivaracetam 50 mg/day BRV 50 mg/day	Drug: Brivaracetam 25 mg Active Substance: Brivaracetam Pharmaceutical Form: Tablet Concentration: 25 mg Route of Administration: Oral use Other Name: ucb34714 Drug: Brivaracetam 50 mg Active Substance: Brivaracetam Pharmaceutical Form: Tablet Concentration: 50 mg Route of Administration: Oral use Other Name: ucb34714
Experimental: Brivaracetam 150 mg/day BRV 150 mg/day	Drug: Brivaracetam 25 mg Active Substance: Brivaracetam Pharmaceutical Form: Tablet Concentration: 25 mg Route of Administration: Oral use Other Name: ucb34714 Drug: Brivaracetam 50 mg Active Substance: Brivaracetam Pharmaceutical Form: Tablet Concentration: 50 mg Route of Administration: Oral use Other Name: ucb34714

Eligibility


Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with diagnosed Unverricht-Lundborg disease (ULD) ascertained by appropriate genetic testing for a homozygous or compound heterozygous mutation in the Cystatin B (CSTB) gene
Subjects with moderate to severe myoclonus documented by an Action Myoclonus sum score of ≥ 30 (evaluation by investigator)
Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator
Subjects currently being or having been treated with valproate up to the maximum recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator

Exclusion Criteria:

Subjects currently on felbamate or having been on felbamate within less than 18 months prior to Visit 1
Subjects currently treated with phenytoin or having been on phenytoin in the last month prior to Visit 1
Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual fields examination report available including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman)
Subject taking any drug with possible central nervous system (CNS) effects
Subjects taking any drug that may significantly influence the metabolism of BRV (CYP2C or CYP3A potent inducers/inhibitors)
Known clinically significant acute or chronic illness or illness which may impair reliable participation in the trial, necessitate the use of medication not allowed by protocol or represent a safety risk in the Investigator's opinion
Subjects with history of severe adverse hematological reaction to any drug
Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT value of more than three times the upper limit of the reference range
History of suicide attempt during the last 5 years
Subject with suicidal ideations within the last year or at risk of suicide attempt unless cleared by written confirmation from a psychiatrist and approved by the UCB physician
Ongoing psychiatric disorder other than mild controlled disorder

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357669

Locations


Finland

Kuopio, Finland

Tampere, Finland
France

Marseille, France

Montpellier Cedex 5, France
Italy

Bologna, Italy

Messina, Italy

Milano, Italy

Napoli, Italy
Netherlands

Heemstede, Netherlands

Heeze, Netherlands
Réunion

St Pierre Cedex, Réunion
Sweden

Goteborg, Sweden
Tunisia

Tunis, Tunisia

Sponsors and Collaborators

UCB Pharma SA

Investigators


Study Director:	UCB Clinical Trial Call Center	+1 877 822 9493 (UCB)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kälviäinen R, Genton P, Andermann E, Andermann F, Magaudda A, Frucht SJ, Schlit AF, Gerard D, de la Loge C, von Rosenstiel P. Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 2016 Feb;57(2):210-21. doi: 10.1111/epi.13275. Epub 2015 Dec 15.


Responsible Party:	UCB Pharma SA
ClinicalTrials.gov Identifier:	NCT00357669 History of Changes
Other Study ID Numbers:	N01187 2006-000169-12
Study First Received:	July 25, 2006
Last Updated:	May 15, 2015
Health Authority:	European Union: European Medicines Agency

Keywords provided by UCB Pharma:


Unverricht-Lundborg disease Baltic myoclonus progressive myoclonic epilepsies myoclonus brivaracetam

Additional relevant MeSH terms:


Unverricht-Lundborg Syndrome Myoclonic Epilepsies, Progressive Epilepsies, Myoclonic Epilepsy Brain Diseases	Central Nervous System Diseases Nervous System Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 28, 2016