Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy - Full Text View

Sponsor:	UCB, Inc.
Information provided by (Responsible Party):	UCB, Inc.
ClinicalTrials.gov Identifier:	NCT01405508

Purpose

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	Intervention	Phase
Epilepsy	Drug: Brivaracetam	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Epilepsy

U.S. FDA Resources

Further study details as provided by UCB, Inc.:

Primary Outcome Measures:

Number of subjects with at least one treatment-emergent adverse event during the study (maximum 40 days) [ Time Frame: 40 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of subjects who withdrew due to a treatment-emergent adverse event during the study (maximum 40 days) [ Time Frame: 40 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	August 2011
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Placebo (PBO) tablets/ Brivatacetam (BRV) bolus	Drug: Brivaracetam Run-In: PBO or BRV tablets administered orally (100 mg/intake bid), according to randomization. Evaluation: BRV administered intravenously (100 mg/administration bid) as a bolus or an infusion according to randomization: Bolus: 10mL (=100mg) of BRV/administration over 2 minutes bid. Infusion: 10mL (=100mg) of BRV/administration diluted in 90mL 0.9% isotonic saline sterile solution for iv administration infused over 15 minutes. 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; 75mg/intake bid for the first week, 50mg/intake bid for the second week, 25mg/intake bid for the third week, and 10mg/intake bid for the fourth week or PBO.
Experimental: BRV tablets/ BRV bolus	Drug: Brivaracetam Run-In: PBO or BRV tablets administered orally (100 mg/intake bid), according to randomization. Evaluation: BRV administered intravenously (100 mg/administration bid) as a bolus or an infusion according to randomization: Bolus: 10mL (=100mg) of BRV/administration over 2 minutes bid. Infusion: 10mL (=100mg) of BRV/administration diluted in 90mL 0.9% isotonic saline sterile solution for iv administration infused over 15 minutes. 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; 75mg/intake bid for the first week, 50mg/intake bid for the second week, 25mg/intake bid for the third week, and 10mg/intake bid for the fourth week or PBO.
Experimental: Placebo tablets/BRV infusion Subjects will receive placebo or BRV tablets for one week followed by BRV iv (bolus or infusion) for 4.5 days	Drug: Brivaracetam Run-In: PBO or BRV tablets administered orally (100 mg/intake bid), according to randomization. Evaluation: BRV administered intravenously (100 mg/administration bid) as a bolus or an infusion according to randomization: Bolus: 10mL (=100mg) of BRV/administration over 2 minutes bid. Infusion: 10mL (=100mg) of BRV/administration diluted in 90mL 0.9% isotonic saline sterile solution for iv administration infused over 15 minutes. 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; 75mg/intake bid for the first week, 50mg/intake bid for the second week, 25mg/intake bid for the third week, and 10mg/intake bid for the fourth week or PBO.
Experimental: BRV tablets/BRV infusion Subjects will receive placebo or BRV tablets for one week followed by BRV iv (bolus or infusion) for 4.5 days.	Drug: Brivaracetam Run-In: PBO or BRV tablets administered orally (100 mg/intake bid), according to randomization. Evaluation: BRV administered intravenously (100 mg/administration bid) as a bolus or an infusion according to randomization: Bolus: 10mL (=100mg) of BRV/administration over 2 minutes bid. Infusion: 10mL (=100mg) of BRV/administration diluted in 90mL 0.9% isotonic saline sterile solution for iv administration infused over 15 minutes. 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; 75mg/intake bid for the first week, 50mg/intake bid for the second week, 25mg/intake bid for the third week, and 10mg/intake bid for the fourth week or PBO.

Detailed Description:

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

Eligibility

Ages Eligible for Study:	16 Years to 70 Years
Genders Eligible for Study:	Both
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 AEDs
Permitted concomitant AEDs and 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 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: ALT, AST, 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 <50mL/min, platelets <100,000/µL, or neutrophil cells <1,800/µL
Clinically significant 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 enrolment (V1)
Investigators, coinvestigators, their spouses or children, or any study collaborators
Subjects previously treated with BRV
Subject previously screened within this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01405508

Contacts

Contact: UCB Clinical Trial Call Center

+1 877 822 9493

Show 24 Study Locations

Sponsors and Collaborators

UCB, Inc.

Investigators

Study Director:

UCB Clinical Trial Call Center

+1 877 822 9493 (UCB)

More Information

No publications provided

Responsible Party:	UCB, Inc.
ClinicalTrials.gov Identifier:	NCT01405508 History of Changes
Other Study ID Numbers:	N01258
Study First Received:	July 27, 2011
Last Updated:	May 11, 2012
Health Authority:	United States: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices Poland: National Institute of Medicines Czech Republic: State Institute for Drug Control

Keywords provided by UCB, Inc.:

N01258
Brivaracetam
Epilepsy
IV
intravenous

Additional relevant MeSH terms:

Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012