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

NCT ID: NCT01405508

Last Updated: 2018-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2012-07-31

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

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Brivaracetam infusion

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

100 mg twice daily (BID) for 7 days during Run-In Period

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

Group Type: EXPERIMENTAL

Brivaracetam tablets

Intervention Type: DRUG

100 mg, intake twice daily (BID) for 7 days during Run-In Period

Brivaracetam infusion

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Brivaracetam bolus

Intervention Type: DRUG

10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period

Placebo

Intervention Type: OTHER

100 mg twice daily (BID) for 7 days during Run-In Period

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

Group Type: EXPERIMENTAL

Brivaracetam tablets

Intervention Type: DRUG

100 mg, intake twice daily (BID) for 7 days during Run-In Period

Brivaracetam bolus

Intervention Type: DRUG

10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period

Interventions

Brivaracetam tablets

100 mg, intake twice daily (BID) for 7 days during Run-In Period

Intervention Type: DRUG

Brivaracetam bolus

10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period

Intervention Type: 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

Intervention Type: DRUG

Placebo

100 mg twice daily (BID) for 7 days during Run-In Period

Intervention Type: OTHER

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UCB Clinical Trial Call Center

Role: STUDY_DIRECTOR

+1 877 822 9493 (UCB)

Locations

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

777

Dallas, Texas, United States

036

Charlottesville, Virginia, United States

917

Brno, , Czechia

915

Hradec Králové, , Czechia

916

Kroměříž, , Czechia

913

Ostrava Poruba, , Czechia

332

Bielefeld, , Germany

903

Bonn, , Germany

795

Katowice, , Poland

479

Poznan, , Poland

794

Warsaw, , Poland

Countries

United States; Czechia; Germany; Poland

References

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.

Reference Type: DERIVED

PMID: 33780735 (View on PubMed)

Other Identifiers

2008-004714-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N01258

Identifier Type: -

Identifier Source: org_study_id