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

• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

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).

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Brivaracetam tablets; Drug: Brivaracetam bolus; Drug: Brivaracetam infusion; Other: Placebo	Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	105 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	August 2011
Actual Primary Completion Date :	July 2012
Actual Study Completion Date :	July 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) [ Time Frame: 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 :

1. Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) [ Time Frame: 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.
2. 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 ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 70 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
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

Locations

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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
Czechia
917
Brno, Czechia
915
Hradec Kralove, Czechia
916
Kromeriz, Czechia
913
Ostrava Poruba, Czechia
Germany
332
Bielefeld, Germany
903
Bonn, Germany
Poland
795
Katowice, Poland
479
Poznan, Poland
794
Warszawa, Poland

Sponsors and Collaborators

UCB Pharma

Investigators

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Study Director:	UCB Clinical Trial Call Center	+1 877 822 9493 (UCB)

More Information

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Responsible Party:	UCB Pharma
ClinicalTrials.gov Identifier:	NCT01405508 History of Changes
Other Study ID Numbers:	N01258; 2008-004714-27 ( EudraCT Number )
First Posted:	July 29, 2011
Results First Posted:	April 13, 2016
Last Update Posted:	July 11, 2018
Last Verified:	July 2016

Keywords provided by UCB Pharma:

N01258; Brivaracetam; Epilepsy; IV; intravenous

Additional relevant MeSH terms:

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Epilepsy; Brain Diseases; Central Nervous System Diseases	Nervous System Diseases; Brivaracetam; Anticonvulsants