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

Primary Purpose

Epilepsy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Brivaracetam tablets
Brivaracetam bolus
Brivaracetam infusion
Placebo
Sponsored by
UCB Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring N01258, Brivaracetam, Epilepsy, IV, intravenous

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 001
  • 775
  • 780
  • 008
  • 778
  • 776
  • 777
  • 036
  • 917
  • 915
  • 916
  • 913
  • 332
  • 903
  • 795
  • 479
  • 794

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo tablets / Brivaracetam bolus

Brivaracetam (BRV) tablets / BRV bolus

Placebo tablets / Brivaracetam infusion

Brivaracetam (BRV) tablets / BRV infusion

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Secondary Outcome Measures

Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Full Information

First Posted
July 27, 2011
Last Updated
June 13, 2018
Sponsor
UCB Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT01405508
Brief Title
Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Pharma

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
Detailed Description
Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
N01258, Brivaracetam, Epilepsy, IV, intravenous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo tablets / Brivaracetam bolus
Arm Type
Experimental
Arm Description
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
Arm Title
Brivaracetam (BRV) tablets / BRV bolus
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo tablets / Brivaracetam infusion
Arm Type
Experimental
Arm Description
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
Arm Title
Brivaracetam (BRV) tablets / BRV infusion
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Brivaracetam tablets
Intervention Description
100 mg, intake twice daily (BID) for 7 days during Run-In Period
Intervention Type
Drug
Intervention Name(s)
Brivaracetam bolus
Intervention Description
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period
Intervention Type
Drug
Intervention Name(s)
Brivaracetam infusion
Intervention Description
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 Period
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
100 mg twice daily (BID) for 7 days during Run-In Period
Primary Outcome Measure Information:
Title
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Description
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
40 days
Secondary Outcome Measure Information:
Title
Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Description
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
40 days
Title
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
Description
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
4.5-day Evaluation Period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
+1 877 822 9493 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
001
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
775
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
780
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
008
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
778
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
776
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
777
City
Dallas
State/Province
Texas
Country
United States
Facility Name
036
City
Charlottesville
State/Province
Virginia
Country
United States
Facility Name
917
City
Brno
Country
Czechia
Facility Name
915
City
Hradec Kralove
Country
Czechia
Facility Name
916
City
Kromeriz
Country
Czechia
Facility Name
913
City
Ostrava Poruba
Country
Czechia
Facility Name
332
City
Bielefeld
Country
Germany
Facility Name
903
City
Bonn
Country
Germany
Facility Name
795
City
Katowice
Country
Poland
Facility Name
479
City
Poznan
Country
Poland
Facility Name
794
City
Warszawa
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
33780735
Citation
Toledo M, Brandt C, Quarato PP, Schulz AL, Cleveland JM, Wagener G, Klein P. Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial. Epilepsy Behav. 2021 May;118:107897. doi: 10.1016/j.yebeh.2021.107897. Epub 2021 Mar 27.
Results Reference
derived

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

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