Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier:
NCT00368251
First received: August 23, 2006
Last updated: April 9, 2015
Last verified: April 2015
  Purpose

The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht-Lundborg Disease (ULD).


Condition Intervention Phase
Unverricht-Lundborg Disease
Other: Placebo
Drug: BRV 2.5 mg
Drug: BRV 25 mg
Drug: BRV 50 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, 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:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Percent change from Baseline on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4) at the end of the Treatment Period or at Early Discontinuation Visit [ Time Frame: From Baseline to end of Treatment Period (Week 14 or Early Discontinuation Visit) ] [ Designated as safety issue: No ]
    The range for Action Myoclonus Score (centrally read) is 0 (best) - 160 (worst). Percent change from Baseline = 100 X ((Baseline UMRS4 - Treatment UMRS4) / Baseline UMRS4). Baseline is defined as the last non-missing value prior or on Randomization Visit.


Secondary Outcome Measures:
  • Percent change from Baseline on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5) at the end of the Treatment Period or at Early Discontinuation Visit [ Time Frame: Baseline to end of Treatment Period (Week 14 or Early Discontinuation Visit) ] [ Designated as safety issue: No ]
    The range for Functional Disability Score is 0 (best) to 28 (worst). Percent change from Baseline = 100 X ((Baseline UMRS5 - Treatment UMRS5) / Baseline UMRS5). Baseline is defined as the last non-missing value prior or on Randomization Visit.

  • Percent change from Baseline on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3) at the end of the Treatment Period or at Early Discontinuation Visit [ Time Frame: Baseline to end of Treatment Period (Week 14 or Early Discontinuation Visit) ] [ Designated as safety issue: No ]
    The range for Stimulus Sensitivity Score is 0 (best) to 17 (worst). Percent change from Baseline = 100 X ((Baseline UMRS3 - Treatment UMRS3) / Baseline UMRS3). Baseline is defined as the last non-missing value prior or on Randomization Visit.

  • Percent change from Baseline on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1) at the end of the Treatment Period or at Early Discontinuation Visit [ Time Frame: Baseline to end of Treatment Period (Week 14 or Early Discontinuation Visit) ] [ Designated as safety issue: No ]
    The range for Myoclonus Patient Questionnaire is 0 (best) to44 (worst). Percent change from Baseline = 100 X ((Baseline UMRS1 - Treatment UMRS1) / Baseline UMRS1). Baseline is defined as the last non-missing value prior or on Randomization Visit.

  • Global Evaluation Scale (I-GES) at the end of the Treatment Period or at Early Discontinuation Visit [ Time Frame: Baseline to end of Treatment Period (Week 14 or Early Discontinuation Visit) ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: November 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Other: Placebo
Pharmaceutical Form: Tablet, Route of Administration: Oral use,
Experimental: Brivaracetam 5 mg/day
Brivaracetam (BRV) 5 mg/day
Drug: BRV 2.5 mg
Active Substance: Brivaracetam, Pharmaceutical Form: Tablet, Concentration: 2.5 mg, Route of Administration: Oral use
Experimental: Brivaracetam 150 mg/day
Brivaracetam (BRV) 150 mg/day
Drug: BRV 25 mg
Active Substance: Brivaracetam, Pharmaceutical Form: Tablet, Concentration: 25 mg, Route of Administration: Oral use
Drug: BRV 50 mg
Active Substance: Brivaracetam, Pharmaceutical Form: Tablet, Concentration: 50 mg, Route of Administration: Oral use,

  Eligibility

Ages Eligible for Study:   16 Years and older
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 CSTB gene
  • Subjects with moderate to severe myoclonus documented by an Action Myoclonussum 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
  • Male/female subjects from 16 years onwards. Subjects under 18 years may only be included where legally permitted and ethically accepted

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: NCT00368251

Locations
United States, California
135
San Francisco, California, United States
United States, Florida
133
Gainesville, Florida, United States
United States, New York
132
New York, New York, United States
United States, Virginia
131
Charlottesville, Virginia, United States
Canada, British Columbia
151
Vancouver, British Columbia, Canada
Canada, Quebec
150
Montreal, Quebec, Canada
Canada
152
Quebec, Canada
Finland
100
Helsinki, Finland
France
122
Bron, France
121
Lille, France
120
Paris, France
Israel
170
Tel Aviv, Israel
Russian Federation
141
Moscow, Russian Federation
143
Samara, Russian Federation
142
St. Petersburg, Russian Federation
Serbia
161
Belgrade, Serbia
162
Belgrade, Serbia
Tunisia
180
La Manouba, Tunisia
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 Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT00368251     History of Changes
Other Study ID Numbers: N01236, RPCE06C2320, 2006-001536-46
Study First Received: August 23, 2006
Last Updated: April 9, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Finland: Finnish National Agency for Medicines
Israel: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Serbia: Medicines and Medical Devices Agency

Keywords provided by UCB Pharma:
Unverricht-Lundborg Disease
Baltic Myoclonus
Progressive Myoclonic Epilepsies
Myoclonus
Brivaracetam

Additional relevant MeSH terms:
Unverricht-Lundborg Syndrome
Brain Diseases
Central Nervous System Diseases
Epilepsies, Myoclonic
Epilepsy
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Myoclonic Epilepsies, Progressive
Nervous System Diseases
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on May 27, 2015