Follow-up Trial to Evaluate Long-term Safety and Efficacy of Brivaracetam in Subjects Suffering From Epilepsy

An Open-label, Multicenter, Follow-up Trial to Evaluate Long-term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment at a Flexible Dose up to a Maximum of 200 mg/Day in Subjects Aged 16 Years or Older Suffering From Epilepsy

This trial, evaluating the long-term safety and tolerability of brivaracetam, will give subjects suffering from epilepsy, who may have benefited from brivaracetam, the opportunity to continue the treatment. The study will also evaluate the maintenance of efficacy over time of brivaracetam for subjects with partial onset seizures (POS)/primary generalized seizures (PGS).

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Brivaracetam (ucb 34714)

• Study Type: Interventional
• Enrollment (Actual): 853
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • 509
  • Innsbruck, Austria
    • 507
  • Linz, Austria
    • 510
  • Wien, Austria
    • 508
• Belgium
  • Brugge, Belgium
    • 506
  • Gent, Belgium
    • 513
  • La Louvière, Belgium
    • 974
  • Leuven, Belgium
    • 505
  • Antwerpen
    • Edegem, Antwerpen, Belgium
      • 501
  • Chaleroi
    • Montignies sur Sambre, Chaleroi, Belgium
      • 515
• Canada
  • Quebec, Canada
    • 952
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 951
  • Quebec
    • Montreal, Quebec, Canada
      • 950
• Czechia
  • Beroun, Czechia
    • 545
  • Brno, Czechia
    • 543
  • Brno, Czechia
    • 544
  • Ceske Budejovice, Czechia
    • 546
  • Ostrava Trebovice, Czechia
    • 519
  • Praha 1, Czechia
    • 541
  • Praha 2, Czechia
    • 517
  • Praha 5, Czechia
    • 542
  • Zlin, Czechia
    • 518
• Finland
  • Helsinki, Finland
    • 900
  • Kuopio, Finland
    • 581
  • Oulu, Finland
    • 526
  • Oulu, Finland
    • 582
  • Seinajoki, Finland
    • 527
  • Tampere, Finland
    • 583
  • Tampere, Finland
    • 811
• France
  • Angers Cedex 1, France
    • 632
  • Bethune, France
    • 628
  • Dijon, France
    • 630
  • Lille, France
    • 624
  • Marseille, France
    • 625
  • Montpellier Cedex 5, France
    • 623
  • Nancy, France
    • 635
  • Paris, France
    • 626
  • Paris, France
    • 920
  • Rennes, France
    • 622
  • Roanne, France
    • 528
  • St Pierre Cedex, France
    • 823
  • Strasbourg, France
    • 627
  • Toulouse Cedex 04, France
    • 634
  • Bron
    • Lyon, Bron, France
      • 633
• Germany
  • Bad Berka, Germany
    • 532
  • Berlin, Germany
    • 705
  • Berlin, Germany
    • 708
  • Bernau, Germany
    • 536
  • Bielefeld, Germany
    • 707
  • Bonn, Germany
    • 701
  • Erlangen, Germany
    • 709
  • Frankfurt, Germany
    • 703
  • Freiburg, Germany
    • 711
  • Göttingen, Germany
    • 537
  • Jena, Germany
    • 535
  • Kehl, Germany
    • 710
  • Liegau-Augustusbad, Germany
    • 531
  • Mainz, Germany
    • 533
  • Munchen, Germany
    • 560
  • Munchen, Germany
    • 706
  • Ulm, Germany
    • 704
• Hong Kong
  • Hong Kong, Hong Kong
    • 649
  • Shatin, Hong Kong
    • 650
• Hungary
  • Budapest, Hungary
    • 547
  • Debrecen, Hungary
    • 538
  • Pecs, Hungary
    • 539
• Israel
  • Tel Aviv, Israel
    • 970
• Italy
  • Bologna, Italy
    • 830
  • Foggia, Italy
    • 553
  • Messina, Italy
    • 831
  • Milano, Italy
    • 563
  • Milano, Italy
    • 832
  • Napoli, Italy
    • 833
  • Pavia, Italy
    • 554
  • Perugia, Italy
    • 550
  • Roma, Italy
    • 552
  • Roma, Italy
    • 555
  • Roma, Italy
    • 559
  • Siena, Italy
    • 973
• Korea, Republic of
  • Gwangju, Korea, Republic of
    • 655
  • Seoul, Korea, Republic of
    • 652
  • Seoul, Korea, Republic of
    • 653
  • Seoul, Korea, Republic of
    • 654
  • Seoul, Korea, Republic of
    • 656
• Netherlands
  • Breda, Netherlands
    • 566
  • Den Haag, Netherlands
    • 567
  • Heemstede, Netherlands
    • 821
  • Heeze, Netherlands
    • 822
• Norway
  • Fredrikstad, Norway
    • 571
  • Oslo, Norway
    • 568
  • Sandvika, Norway
    • 569
  • Trondheim, Norway
    • 570
• Poland
  • Bialystok, Poland
    • 575
  • Gdansk, Poland
    • 741
  • Grodzisk Mazowiecki, Poland
    • 978
  • Katowice, Poland
    • 748
  • Katowice, Poland
    • 976
  • Kielce, Poland
    • 574
  • Krakow, Poland
    • 975
  • Lodz, Poland
    • 744
  • Lodz, Poland
    • 747
  • Lublin, Poland
    • 742
  • Poznan, Poland
    • 977
  • Szczecin, Poland
    • 746
  • Warsaw, Poland
    • 573
  • Warszawa, Poland
    • 576
  • Warszawa, Poland
    • 577
  • Warszawa, Poland
    • 743
  • Warszawa, Poland
    • 745
• Russian Federation
  • Kazan, Russian Federation
    • 591
  • Moscow, Russian Federation
    • 578
  • Moscow, Russian Federation
    • 579
  • Moscow, Russian Federation
    • 584
  • Moscow, Russian Federation
    • 586
  • Moscow, Russian Federation
    • 588
  • Samara, Russian Federation
    • 943
  • St. Petersburg, Russian Federation
    • 589
  • Yaroslavl, Russian Federation
    • 587
• Serbia
  • Belgrade, Serbia
    • 961
  • Belgrade, Serbia
    • 962
• Singapore
  • Singapore, Singapore
    • 657
• South Africa
  • George, South Africa
    • 648
• Spain
  • Barcelona, Spain
    • 593
  • Madrid, Spain
    • 594
  • Madrid, Spain
    • 783
  • Madrid, Spain
    • 786
  • San Sebastian, Spain
    • 596
  • Vigo, Spain
    • 595
  • Zaragoza, Spain
    • 597
  • Madrid
    • Alcorcón, Madrid, Spain
      • 599
• Sweden
  • Goteborg, Sweden
    • 850
  • Stockholm, Sweden
    • 601
  • Umea, Sweden
    • 604
• Switzerland
  • Biel, Switzerland
    • 605
  • St. Gallen, Switzerland
    • 607
  • Tschugg, Switzerland
    • 606
  • Zurich, Switzerland
    • 608
• Taiwan
  • Taichung, Taiwan
    • 671
  • Taichung, Taiwan
    • 672
  • Tainan, Taiwan
    • 669
  • Taoyuan, Taiwan
    • 660
• Tunisia
  • Manouba, Tunisia
    • 861
  • Tunis, Tunisia
    • 860
• Ukraine
  • Donetsk, Ukraine
    • 638
  • Kharkov, Ukraine
    • 637
  • Kyiv, Ukraine
    • 641
  • Kyiv, Ukraine
    • 642
  • Lviv, Ukraine
    • 639
  • Odessa, Ukraine
    • 643
  • Uzhgorod, Ukraine
    • 640
• United States
  • California
    • San Francisco, California, United States, 94115
      • 935
  • Florida
    • Gainesville, Florida, United States, 32610
      • 933
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • 931

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male/female subjects from 16 years (where legally permitted and ethically accepted) or 18 years onwards suffering from epilepsy and having completed a previous study with brivaracetam as adjunctive treatment, which allowed access to this study
• Subjects with POS/PGS: inpatients or outpatients with epilepsy who participated in previous brivaracetam studies / programs which allow access to the present study
• Subjects with ULD: inpatients or outpatients with epilepsy who were treated with brivaracetam in previous studies / programs which allow access to the present study
• Subjects for whom the Investigator believes a reasonable benefit from the long-term administration of brivaracetam may be expected

Exclusion Criteria:

• Severe medical, neurological and psychiatric disorders, or laboratory values which may have an impact on the safety of the subject
• Poor compliance with visit schedule or medication intake in previous brivaracetam study
• Participation in any clinical study of another investigational drug or device during the study
• Pregnant or lactating woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Brivaracetam; Flexible dosing, can up and down titrate as needed.

Drug: Brivaracetam (ucb 34714); 10 mg and 25 mg tablets. Flexible dosing up to 200 mg/day, twice daily. For each subject, the study will last from study entry until either regulatory approval of brivaracetam has been granted by any Health Authority in an indication of adjunctive treatment of partial onset seizures; or until the Sponsor decides to close the study; until a managed access program, named patient program, compassionate use program, or similar type of access program is established as allowed per country-specific requirements in addition to legal and regulatory guidelines, or until the investigational product development is stopped by the Sponsor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	Treatment-emergent adverse events (TEAEs) were defined as those events which started on or after the date of first dose of investigational medicinal product (IMP), or events in which severity worsened on or after the date of first dose of study medication. The event does not necessarily have a causal relationship with that treatment or usage.	From Entry Visit until Last Visit (up to 162 months)
Percentage of Participants Who Withdrew Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.	From Entry Visit until Last Visit (up to 162 months)
Percentage of Participants With at Least One Serious Adverse Event (SAE)	A serious adverse event (SAE) is any untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Is an infection that requires treatment parenteral antibiotics; Other important medical events which based on medical or scientific judgement may jeopardize the patients or may require medical or surgical intervention to prevent any of the above.	From Entry Visit until Last Visit (up to 162 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period	The 28 day adjusted seizure frequency was calculated by dividing the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 [NCT00175929], N01252 [NCT00490035] and N01254 [NCT00504881].	From Entry Visit until Last Visit (up to 162 months)
Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period	The percent change from the previous study baselines, in Partial Onset Seizure (POS) (Type I) frequency per 28 days is defined as: (the value at the previous study baselines) minus (the value at each time-points during the evaluation period) divided by the value at the previous study baselines. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 [NCT00175929], N01252 [NCT00490035] and N01254 [NCT00504881].	From Entry Visit until Last Visit (up to 162 months)
Responder Rate in POS (Type I) Frequency Over the Evaluation Period	A responder is defined as a participant with a ≥ 50% reduction in seizure frequency from the Baseline Period of the previous study. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 [NCT00175929], N01252 [NCT00490035] and N01254 [NCT00504881].	From Entry Visit until Last Visit (up to 162 months)

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Markham A. Brivaracetam: First Global Approval. Drugs. 2016 Mar;76(4):517-22. doi: 10.1007/s40265-016-0555-6.
• Moseley BD, Dimova S, Elmoufti S, Laloyaux C, Asadi-Pooya AA. Long-term efficacy and tolerability of adjunctive brivaracetam in adults with focal to bilateral tonic-clonic (secondary generalized) seizures: Post hoc pooled analysis. Epilepsy Res. 2021 Oct;176:106694. doi: 10.1016/j.eplepsyres.2021.106694. Epub 2021 Jun 24.
• 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.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2005
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): August 17, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Epilepsy; Brivaracetam; long term
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Anticonvulsants; Brivaracetam
• Other Study ID Numbers: N01125; 2004-002140-10 (EudraCT Number)