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Trial record 1 of 2 for:    NCT01405508
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Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy

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ClinicalTrials.gov Identifier: NCT01405508
Recruitment Status : Completed
First Posted : July 29, 2011
Results First Posted : April 13, 2016
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
UCB Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: Brivaracetam tablets
Drug: Brivaracetam bolus
Drug: Brivaracetam infusion
Other: Placebo
Enrollment 105
Recruitment Details

This study started to recruit patients in August 2011 and concluded in July 2012.

105 subjects were randomized to 4 different treatment groups.

Pre-assignment Details Participant Flow refers to the Randomized Set (RS).
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Hide Arm/Group Description

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

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

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

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

Period Title: Overall Study
Started 26 26 27 26
Completed 25 25 27 26
Not Completed 1 1 0 0
Reason Not Completed
AE, non-serious non-fatal             1             1             0             0
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion Total Title
Hide Arm/Group Description

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

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

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

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

[Not Specified]
Overall Number of Baseline Participants 26 26 27 26 105
Hide Baseline Analysis Population Description
Baseline Characetristics refer to the Safety Population consisting of all subjects who took at least 1 dose of study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 26 participants 27 participants 26 participants 105 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
 100.0%
25
  96.2%
27
 100.0%
25
  96.2%
103
  98.1%
>=65 years
0
   0.0%
1
   3.8%
0
   0.0%
1
   3.8%
2
   1.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 26 participants 27 participants 26 participants 105 participants
40.6  (12.2) 39.5  (14.4) 42.0  (9.2) 44.4  (12.6) 41.6  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 26 participants 27 participants 26 participants 105 participants
Female
12
  46.2%
10
  38.5%
17
  63.0%
17
  65.4%
56
  53.3%
Male
14
  53.8%
16
  61.5%
10
  37.0%
9
  34.6%
49
  46.7%
1.Primary Outcome
Title Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Hide Description 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.
Time Frame 40 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisting of all subjects who took at least 1 dose of study drug.
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Hide Arm/Group Description:

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

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

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

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

Overall Number of Participants Analyzed 26 26 27 26
Measure Type: Number
Unit of Measure: Participants
20 19 21 20
2.Secondary Outcome
Title Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Hide Description 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.
Time Frame 40 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisting of all subjects who took at least 1 dose of study drug.
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Hide Arm/Group Description:

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

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

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

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

Overall Number of Participants Analyzed 26 26 27 26
Measure Type: Number
Unit of Measure: Participants
1 1 0 0
3.Secondary Outcome
Title Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
Hide Description 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.
Time Frame 4.5-day Evaluation Period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population consisting of all subjects who took at least 1 dose of study drug.
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Hide Arm/Group Description:

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

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

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

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

Overall Number of Participants Analyzed 26 26 27 26
Measure Type: Number
Unit of Measure: Participants
1 3 4 3
Time Frame Adverse Events were collected from Baseline over Run-In (Day 1) and Evaluation Period (Day 8 to Day 12) to the Safety Visit or Early Discontinuation Visit (up to 54 days).
Adverse Event Reporting Description Adverse Events refer to the Safety Population consisting of all subjects who took at least 1 dose of study drug.
 
Arm/Group Title Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Hide Arm/Group Description

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

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

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

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

All-Cause Mortality
Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/26 (0.00%)      0/26 (0.00%)      0/27 (0.00%)      0/26 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Tablets / Brivaracetam Bolus Placebo Tablets / Brivaracetam Infusion Brivaracetam (BRV) Tablets / BRV Bolus Brivaracetam (BRV) Tablets / BRV Infusion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/26 (65.38%)      15/26 (57.69%)      15/27 (55.56%)      14/26 (53.85%)    
Cardiac disorders         
Postural orthostatic tachycardia syndrome * 1  2/26 (7.69%)  2 0/26 (0.00%)  0 1/27 (3.70%)  1 0/26 (0.00%)  0
Ear and labyrinth disorders         
Vertigo * 1  1/26 (3.85%)  1 1/26 (3.85%)  1 2/27 (7.41%)  2 1/26 (3.85%)  1
Gastrointestinal disorders         
Dyspepsia * 1  1/26 (3.85%)  1 0/26 (0.00%)  0 2/27 (7.41%)  2 0/26 (0.00%)  0
General disorders         
Fatigue * 1  1/26 (3.85%)  1 2/26 (7.69%)  4 3/27 (11.11%)  4 0/26 (0.00%)  0
Infusion site pain * 1  0/26 (0.00%)  0 3/26 (11.54%)  3 2/27 (7.41%)  2 0/26 (0.00%)  0
Injection site erythema * 1  0/26 (0.00%)  0 0/26 (0.00%)  0 2/27 (7.41%)  2 0/26 (0.00%)  0
Injection site pain * 1  0/26 (0.00%)  0 0/26 (0.00%)  0 2/27 (7.41%)  2 0/26 (0.00%)  0
Nervous system disorders         
Somnolence * 1  8/26 (30.77%)  8 7/26 (26.92%)  7 7/27 (25.93%)  9 9/26 (34.62%)  10
Dizziness * 1  4/26 (15.38%)  4 4/26 (15.38%)  4 3/27 (11.11%)  3 4/26 (15.38%)  4
Headache * 1  2/26 (7.69%)  2 1/26 (3.85%)  1 2/27 (7.41%)  3 2/26 (7.69%)  2
Dysgeusia * 1  2/26 (7.69%)  2 0/26 (0.00%)  0 2/27 (7.41%)  2 0/26 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough * 1  0/26 (0.00%)  0 2/26 (7.69%)  2 0/27 (0.00%)  0 0/26 (0.00%)  0
Skin and subcutaneous tissue disorders         
Rash * 1  3/26 (11.54%)  3 1/26 (3.85%)  1 0/27 (0.00%)  0 0/26 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: UCB (Study Director)
Organization: UCB Cares
Phone: +1 887 822 9493
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT01405508     History of Changes
Other Study ID Numbers: N01258
2008-004714-27 ( EudraCT Number )
First Submitted: July 27, 2011
First Posted: July 29, 2011
Results First Submitted: March 14, 2016
Results First Posted: April 13, 2016
Last Update Posted: July 11, 2018