Clinical trial NCT00368251: Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Unverricht-Lundborg Disease
Keywords: Unverricht-Lundborg Disease
Baltic Myoclonus
Progressive Myoclonic Epilepsies
Myoclonus
Brivaracetam
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2006-08-24
Enrollment: 56
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)
timeFrame: From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Secondary outcomes:
measure: Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)
timeFrame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
measure: Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)
timeFrame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
measure: Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)
timeFrame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
measure: Global Evaluation Score (Investigator) at the End of Treatment Period
timeFrame: End of Treatment Period (Week 14 or Early Discontinuation Visit)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: 135
state: California
city: Gainesville
country: United States
facility: 133
state: Florida
city: New York
country: United States
facility: 132
state: New York
city: Charlottesville
country: United States
facility: 131
state: Virginia
city: Vancouver
country: Canada
facility: 151
state: British Columbia
city: Montreal
country: Canada
facility: 150
state: Quebec
city: Quebec
country: Canada
facility: 152
city: Helsinki
country: Finland
facility: 100
city: Bron
country: France
facility: 122
city: Lille
country: France
facility: 121
city: Paris
country: France
facility: 120
city: Tel Aviv
country: Israel
facility: 170
city: Moscow
country: Russian Federation
facility: 141
city: Saint Petersburg
country: Russian Federation
facility: 142
city: Samara
country: Russian Federation
facility: 143
city: Belgrade
country: Serbia
facility: 161
city: Belgrade
country: Serbia
facility: 162
city: La Manouba
country: Tunisia
facility: 180
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C. Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial. Epilepsy Res. 2021 Feb;170:106526. doi: 10.1016/j.eplepsyres.2020.106526. Epub 2020 Dec 4.
citation: Kalviainen 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.