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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01405508
• Other study ID #: N01258
• Secondary ID: 2008-004714-27
• Status: Completed
• Phase: Phase 3
• Start date: August 2011
• Est. completion date: July 2012

Study information

• Verified date: July 2016
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy

Intervention

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

Locations

Country	Name	City	State
Czechia	917	Brno
Czechia	915	Hradec Kralove
Czechia	916	Kromeriz
Czechia	913	Ostrava Poruba
Germany	332	Bielefeld
Germany	903	Bonn
Poland	795	Katowice
Poland	479	Poznan
Poland	794	Warszawa
United States	008	Bethesda	Maryland
United States	036	Charlottesville	Virginia
United States	778	Columbus	Ohio
United States	777	Dallas	Texas
United States	780	Lexington	Kentucky
United States	775	Little Rock	Arkansas
United States	776	Nashville	Tennessee
United States	001	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	40 days
Secondary	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.	40 days
Secondary	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.	4.5-day Evaluation Period