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

NCT01405508 | Completed Phase 3 Results

• 2 other identifiers: N012582008-004714-27
• Study Type: interventional
• Target: 105
• Locations: 4 countries
• Sites: 17

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).

Conditions

Epilepsy

Keywords

N01258; Brivaracetam; Epilepsy; IV; intravenous

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)

  40 days

• Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.

  4.5-day Evaluation Period

Study Arms (4)

Placebo tablets / Brivaracetam bolus

EXPERIMENTAL

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; Other: Placebo

Brivaracetam (BRV) tablets / BRV bolus

EXPERIMENTAL

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; Drug: Brivaracetam bolus

Placebo tablets / Brivaracetam infusion

EXPERIMENTAL

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; Other: Placebo

Brivaracetam (BRV) tablets / BRV infusion

EXPERIMENTAL

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; Drug: Brivaracetam infusion

Interventions

Brivaracetam tablets DRUG

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

Brivaracetam (BRV) tablets / BRV bolus; Brivaracetam (BRV) tablets / BRV infusion

Brivaracetam bolus DRUG

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

Brivaracetam (BRV) tablets / BRV bolus; Placebo tablets / Brivaracetam bolus

Brivaracetam infusion 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

Brivaracetam (BRV) tablets / BRV infusion; Placebo tablets / Brivaracetam infusion

Placebo OTHER

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

Placebo tablets / Brivaracetam bolus; Placebo tablets / Brivaracetam infusion

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Pharma: lead

Study Sites (17)

001

Phoenix, Arizona, United States

Location

775

Little Rock, Arkansas, United States

Location

780

Lexington, Kentucky, United States

Location

008

Bethesda, Maryland, United States

Location

778

Columbus, Ohio, United States

Location

776

Nashville, Tennessee, United States

Location

777

Dallas, Texas, United States

Location

036

Charlottesville, Virginia, United States

Location

917

Brno, Czechia

Location

915

Hradec Králové, Czechia

Location

916

Kroměříž, Czechia

Location

913

Ostrava Poruba, Czechia

Location

332

Bielefeld, Germany

Location

903

Bonn, Germany

Location

795

Katowice, Poland

Location

479

Poznan, Poland

Location

794

Warsaw, Poland

Location

Related Publications (1)

• 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.

  PMID: 33780735 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: UCB (Study Director)
• Organization: UCB Cares

+1 887 822 9493

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: July 29, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 11, 2018
• Results First Posted: April 13, 2016

Record last verified: 2016-07

Locations

US (8); PL (3); DE (2); CZ (4)