Clinical trial NCT01405508: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: N01258
Brivaracetam
Epilepsy
IV
intravenous
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 105
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
timeFrame: 40 days
Secondary outcomes:
measure: Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
timeFrame: 40 days
measure: Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
timeFrame: 4.5-day Evaluation Period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 001
state: Arizona
city: Little Rock
country: United States
facility: 775
state: Arkansas
city: Lexington
country: United States
facility: 780
state: Kentucky
city: Bethesda
country: United States
facility: 008
state: Maryland
city: Columbus
country: United States
facility: 778
state: Ohio
city: Nashville
country: United States
facility: 776
state: Tennessee
city: Dallas
country: United States
facility: 777
state: Texas
city: Charlottesville
country: United States
facility: 036
state: Virginia
city: Brno
country: Czechia
facility: 917
city: Hradec Kralove
country: Czechia
facility: 915
city: Kromeriz
country: Czechia
facility: 916
city: Ostrava Poruba
country: Czechia
facility: 913
city: Bielefeld
country: Germany
facility: 332
city: Bonn
country: Germany
facility: 903
city: Katowice
country: Poland
facility: 795
city: Poznan
country: Poland
facility: 479
city: Warszawa
country: Poland
facility: 794
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
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.