Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT01405508
First received: July 27, 2011
Last updated: August 26, 2014
Last verified: July 2013
  Purpose

This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).


Condition Intervention Phase
Epilepsy
Drug: Brivaracetam tablets
Drug: Brivaracetam bolus
Drug: Brivaracetam infusion
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Four-arm, Randomized Trial Evaluating the Safety and Tolerability of Brivaracetam Intravenous Infusion and Bolus, Administered in BID Regimen as an Adjunctive Antiepileptic Treatment in Subjects From 16 to 70 Years Suffering From Epilepsy

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Number of subjects with at least one treatment-emergent adverse event during the study (maximum 40 days) [ Time Frame: 40 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of subjects who withdrew due to a treatment-emergent adverse event during the study (maximum 40 days) [ Time Frame: 40 days ] [ Designated as safety issue: No ]
  • Number of subjects with at least one injection-related treatment-emergent adverse event (TEAE) during the Evaluation Period. [ Time Frame: 4.5-day Evaluation Period ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: August 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo tablets / Brivatacetam bolus

Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days.

Down-Titration:

  • If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
  • If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration:

Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Drug: Brivaracetam bolus
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Phase
Other: Placebo
100 mg twice daily (BID) for 7 days during Run-In Phase
Experimental: Brivaracetam (BRV) tablets / BRV bolus

Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days.

Down-Titration:

  • If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
  • If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:

Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week

Drug: Brivaracetam tablets
100 mg, intake twice daily (BID) for 7 days during Run-In Phase
Drug: Brivaracetam bolus
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Phase
Experimental: Placebo tablets / Brivaracetam infusion

Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days.

Down-Titration:

  • If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
  • If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:

Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Drug: Brivaracetam infusion
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Phase
Other: Placebo
100 mg twice daily (BID) for 7 days during Run-In Phase
Experimental: Brivaracetam (BRV) tablets / BRV infusion

Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days.

Down-Titration:

  • If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
  • If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:

Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Drug: Brivaracetam tablets
100 mg, intake twice daily (BID) for 7 days during Run-In Phase
Drug: Brivaracetam infusion
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Phase

Detailed Description:

Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative
  • Subjects from 16 to 70 years
  • Subjects with a body weight of >/= 40 kg
  • Female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method
  • Subject/legal representative considered as reliable and capable of adhering to the protocol
  • Subjects with well-characterized focal or generalized epilepsy or epileptic syndrome
  • Subjects with a history of partial-onset seizures whether or not secondarily generalized or primary generalized seizures
  • Subjects being uncontrolled while treated with 1 to 2 permitted concomitant antiepileptic drugs (AEDs)
  • Permitted concomitant antiepileptic drugs (AEDs) and vagus nerve stimulation (VNS) being stable and at optimal dosage for the subject from at least 1 month before Visit 1 and expected to be kept stable during the Run-In and Evaluation Periods

Exclusion Criteria:

  • Mentally impaired subjects unable to understand the study purpose
  • History or presence of status epilepticus during 1 year preceding Visit 1 or Baseline
  • Subjects on felbamate with less than 18 months continuous exposure before Visit 1
  • Subjects currently on vigabatrin
  • Subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before Visit 1 and expected to be kept stable during the trial
  • Subjects taking any drug that may significantly influence the metabolism of Brivaracetam (BRV) except if the dose has been kept stable at least 1 month before Visit 1, and is expected to be kept stable during the trial
  • History of cerebrovascular accident in the last 6 months
  • Subjects suffering from severe cardiovascular disease or peripheral vascular disease
  • Presence of any sign suggesting rapidly progressing brain disorder or brain tumor
  • Any clinical conditions which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
  • Presence of a terminal illness
  • Presence of a serious infection
  • Subjects with a history of sever adverse hematologic reaction to any drug
  • Subjects suffering from severe disturbance of hemostasis
  • Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) values of more than 3 times the upper limit of the reference range
  • Subjects having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated < 50 ml / min, platelets < 100,000 / µL, or neutrophil cells < 1,800 / µL
  • Clinically significant electrocardiogram (ECG) abnormalities according to the Investigator
  • History of suicide attempt
  • In the Investigator's medical judgment, any current suicidal ideation or other serious psychiatric disorders requiring of having required hospitalization or medication
  • Known allergic reaction or intolerance to pyrrolidone derivatives and / or investigational product excipients
  • Known multiple drug allergies or severe drug allergy
  • Pregnant or lactating women
  • Known alcohol or drug addiction or abuse within the last 2 years
  • Subject institutionalized under judicial decision
  • Problems of venous accessibility
  • Subject taking part in another clinical / pharmacological study in the month preceding enrollment (Visit 1)
  • Investigators, coinvestigators, their spouses or children, or any study collaborators
  • Subjects previously treated with Brivaracetam (BRV)
  • Subject previously screened within this study
  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: NCT01405508

Locations
United States, Arizona
001
Phoenix, Arizona, United States
United States, Arkansas
775
Little Rock, Arkansas, United States
United States, Kentucky
780
Lexington, Kentucky, United States
United States, Maryland
008
Bethesda, Maryland, United States
United States, Ohio
778
Columbus, Ohio, United States
United States, Tennessee
776
Nashville, Tennessee, United States
United States, Texas
777
Dallas, Texas, United States
United States, Virginia
036
Charlottesville, Virginia, United States
Czech Republic
917
Brno, Czech Republic
915
Hradec Kralove, Czech Republic
916
Kromeriz, Czech Republic
913
Ostrava Poruba, Czech Republic
Germany
332
Bielefeld, Germany
903
Bonn, Germany
Poland
795
Katowice, Poland
479
Poznan, Poland
794
Warszawa, Poland
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT01405508     History of Changes
Other Study ID Numbers: N01258, 2008-004714-27
Study First Received: July 27, 2011
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Poland: National Institute of Medicines
Czech Republic: State Institute for Drug Control

Keywords provided by UCB Pharma:
N01258
Brivaracetam
Epilepsy
IV
intravenous

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Central Nervous System Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014