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

Phase 3

Completed

Conditions: Epilepsy

Interventions: Drug: Brivaracetam tablets
Drug: Brivaracetam bolus
Drug: Brivaracetam infusion
Other: Placebo

Registration Number: NCT01405508

Lead Sponsor: UCB Pharma

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 105

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo tablets / Brivaracetam bolus	Placebo	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
Placebo tablets / Brivaracetam infusion	Placebo	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
Brivaracetam (BRV) tablets / BRV bolus	Brivaracetam tablets	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
Brivaracetam (BRV) tablets / BRV infusion	Brivaracetam tablets	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
Placebo tablets / Brivaracetam bolus	Brivaracetam 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
Brivaracetam (BRV) tablets / BRV bolus	Brivaracetam 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
Placebo tablets / Brivaracetam infusion	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
Brivaracetam (BRV) tablets / BRV infusion	Brivaracetam 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

Primary Outcome Measures

Name	Time	Method
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)	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

Name	Time	Method
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.	4.5-day 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.
Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)	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.

Trial Locations

Locations (17): 777
🇺🇸
Dallas, Texas, United States
001
🇺🇸
Phoenix, Arizona, United States
775
🇺🇸
Little Rock, Arkansas, United States
780
🇺🇸
Lexington, Kentucky, United States
008
🇺🇸
Bethesda, Maryland, United States
778
🇺🇸
Columbus, Ohio, United States
776
🇺🇸
Nashville, Tennessee, United States
036
🇺🇸
Charlottesville, Virginia, United States
915
🇨🇿
Hradec Kralove, Czechia
916
🇨🇿
Kromeriz, Czechia
913
🇨🇿
Ostrava Poruba, Czechia
903
🇩🇪
Bonn, Germany
795
🇵🇱
Katowice, Poland
479
🇵🇱
Poznan, Poland
794
🇵🇱
Warszawa, Poland
332
🇩🇪
Bielefeld, Germany
917
🇨🇿
Brno, Czechia