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

NCT00357669 | Completed Phase 3

• 2 other identifiers: N011872006-000169-12
• Study Type: interventional
• Target: 50
• Locations: 7 countries
• Sites: 13

Brief Summary

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

Conditions

Unverricht-Lundborg Disease

Keywords

Unverricht-Lundborg disease; Baltic myoclonus; progressive myoclonic epilepsies; myoclonus; brivaracetam

Outcome Measures

Primary Outcomes (1)

• Percent reduction from baseline on the Action Myoclonus score (Unified Myoclonus Rating Scale (UMRS) Section 4) at the end of the Treatment Period

  End of treatment period (Week 14 or early discontinuation visit)

Secondary Outcomes (4)

• Percent reduction from baseline on the functional disability score (UMRS Section 5) at the end of the Treatment Period

  End of treatment period (week 14 or early discontinuation visit)

• Percent reduction from baseline on the stimulus sensitivity score (UMRS Section 3) at the end of the Treatment Period

  End of treatment period (week 14 or early discontinuation visit)

• Percent reduction from baseline on the myoclonus patient questionnaire (UMRS Section 1) at the end of the Treatment Period

  End of treatment period (week 14 or early discontinuation visit)

• Global Evaluation Scale by Investigator (I-GES) at the end of the Treatment Period

  End of treatment period (week 14 or early discontinuation visit)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Other: Placebo

Brivaracetam 50 mg/day

EXPERIMENTAL

BRV 50 mg/day

Drug: Brivaracetam 25 mg; Drug: Brivaracetam 50 mg

Brivaracetam 150 mg/day

EXPERIMENTAL

BRV 150 mg/day

Drug: Brivaracetam 25 mg; Drug: Brivaracetam 50 mg

Interventions

Brivaracetam 25 mg DRUG

* Active Substance: Brivaracetam * Pharmaceutical Form: Tablet * Concentration: 25 mg * Route of Administration: Oral use

Also known as: ucb34714

Brivaracetam 150 mg/day; Brivaracetam 50 mg/day

Brivaracetam 50 mg DRUG

* Active Substance: Brivaracetam * Pharmaceutical Form: Tablet * Concentration: 50 mg * Route of Administration: Oral use

Also known as: ucb34714

Brivaracetam 150 mg/day; Brivaracetam 50 mg/day

Placebo OTHER

* Active Substance: Placebo Pharmaceutical Form: Tablet * Concentration: 25 mg and 50 mg * Route of Administration: Oral use

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Pharma SA: lead

Study Sites (13)

Unknown Facility

Kuopio, Finland

Location

Unknown Facility

Tampere, Finland

Location

Unknown Facility

Marseille, France

Location

Unknown Facility

Montpellier, France

Location

Unknown Facility

Bologna, Italy

Location

Unknown Facility

Messina, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Napoli, Italy

Location

Unknown Facility

Heemstede, Netherlands

Location

Unknown Facility

Heeze, Netherlands

Location

Unknown Facility

Saint Pierre Cedex, Reunion

Location

Unknown Facility

Gothenburg, Sweden

Location

Unknown Facility

Tunis, Tunisia

Location

Related Publications (2)

• 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.

  PMID: 33461041 DERIVED

• 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.

  PMID: 26666500 DERIVED

MeSH Terms

Conditions

Unverricht-Lundborg Syndrome; Myoclonic Epilepsies, Progressive; Myoclonus

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2006
• First Posted: July 27, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: May 18, 2015

Record last verified: 2015-05

Locations

TU (1); RE (1); SE (1); FI (2); FR (2); IT (4); NL (2)