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Trial record 1 of 1 for:    NCT01339559
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Brivaracetam Safety and Efficacy Follow-up Study in Subjects With Epilepsy (BRITE™)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01339559
Recruitment Status : Completed
First Posted : April 20, 2011
Results First Posted : June 4, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Drug: Brivaracetam
Enrollment 767
Recruitment Details The study started to enroll patients in May 2011 and concluded in April 2019. 767 participants were included in the Enrolled Set but 1 participant from the United States of America was lost to follow-up and was excluded from the Safety Analysis Set.
Pre-assignment Details Participants Flow refers to the Safety Set (SS).
Arm/Group Title Brivaracetam
Hide Arm/Group Description Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period.
Period Title: Overall Study
Started 766
Completed 368
Not Completed 398
Reason Not Completed
Adverse Event             92
Death             5
Lack of Efficacy             164
Lost to Follow-up             22
Subject choice             89
Protocol Violation             15
Study closure at site             1
Incarcerated             2
Epilepsy surgery             1
Pregnancy planned             2
Left the country             1
Investigator decision             2
Patient didn't wish to continue             1
PI decision             1
Arm/Group Title Brivaracetam
Hide Arm/Group Description Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period.
Overall Number of Baseline Participants 766
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Safety Set which consisted of all participants who took at least 1 dose of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 766 participants
<=18 years
19
   2.5%
Between 18 and 65 years
722
  94.3%
>=65 years
25
   3.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 766 participants
40.0  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 766 participants
Female
396
  51.7%
Male
370
  48.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 766 participants
White
561
  73.2%
African-American
37
   4.8%
Asian
85
  11.1%
Other
77
  10.1%
Missing
6
   0.8%
1.Primary Outcome
Title Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Hide Description Treatment-emergent Adverse Events (TEAEs) were defined as those events which started on or after the date of first dose of investigational medicinal product (IMP), or events in which severity worsened on or after the date of first dose of study medication. The event does not necessarily have a causal relationship with that treatment or usage.
Time Frame From Entry Visit (Month 0) until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all participants who took at least 1 dose of study drug.
Arm/Group Title Brivaracetam (SS)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Safety Set (SS).
Overall Number of Participants Analyzed 766
Measure Type: Number
Unit of Measure: Percentage of participants
83.9
2.Primary Outcome
Title Percentage of Participants Who Withdrew Due to Adverse Events (AEs)
Hide Description An AE is any untoward medical occurrence in a participant or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.
Time Frame From Entry Visit (Month 0) until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all participants who took at least 1 dose of study drug.
Arm/Group Title Brivaracetam (SS)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Safety Set (SS).
Overall Number of Participants Analyzed 766
Measure Type: Number
Unit of Measure: Percentage of participants
11.9
3.Primary Outcome
Title Percentage of Participants With at Least One Serious Adverse Event (SAE)
Hide Description

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

  • Results in death
  • Is life-threatening
  • Requires in patient hospitalization or prolongation of existing hospitalization
  • Is a congenital anomaly or birth defect
  • Is as infection that requires treatment parenteral antibiotics
  • Other important medical events which based on medical or scientific judgement may jeopardize the patients or may require medical or surgical intervention to prevent any of the above.
Time Frame From Entry Visit (Month 0) until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set (SS) consisted of all participants who took at least 1 dose of study drug.
Arm/Group Title Brivaracetam (SS)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Safety Set (SS).
Overall Number of Participants Analyzed 766
Measure Type: Number
Unit of Measure: Percentage of participants
18.4
4.Secondary Outcome
Title Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period
Hide Description The 28 day adjusted seizure frequency was calculated by dividing the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28.
Time Frame From Baseline of the previous study until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Partial Onset Seizure (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.
Arm/Group Title Brivaracetam (POS Efficacy)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Partial Onset Seizure Efficacy Set (POS Efficacy).
Overall Number of Participants Analyzed 749
Median (Inter-Quartile Range)
Unit of Measure: Seizures per 28 days
Baseline
9.7
(5.5 to 23.7)
On Treatment
4.2
(1.4 to 12.7)
5.Secondary Outcome
Title Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period
Hide Description

The percent change from the previous study baselines, in Partial Onset Seizure (POS) (Type I) frequency per 28 days is defined as:

(the value at the previous study baselines) minus (the value at each time-points during the evaluation period) divided by the value at the previous study baselines.

Note: Since N01258 was a safety study, participants were not required to meet seizure frequency requirements during the Baseline Period, and the Baseline Period was short (ie, 7 days). Therefore, participants from N01258 were excluded from efficacy summaries in the variable of percent change in POS frequency.

Time Frame From Baseline of the previous study until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The Partial Onset Seizure (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.

Participants from N01258 were excluded from this analysis.

Arm/Group Title Brivaracetam (POS Efficacy)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Partial Onset Seizure Efficacy Set (POS Efficacy).
Overall Number of Participants Analyzed 675
Median (Inter-Quartile Range)
Unit of Measure: Percent change
52.0
(16.8 to 81.5)
6.Secondary Outcome
Title Responder Rate in POS (Type I) Frequency Over the Evaluation Period
Hide Description

A responder is defined as a subject with a ≥ 50% reduction in seizure frequency from the Baseline Period of the previous study.

Note: Since N01258 was a safety study, participants were not required to meet seizure frequency requirements during the Baseline Period, and the Baseline Period was short (ie, 7 days). Therefore, participants from N01258 were excluded from efficacy summaries in the variable of responder rates in POS frequency.

Time Frame From Baseline of the previous study until the Last Visit (up to 84 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The Partial Onset Seizure (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.

Participants from N01258 were excluded from this analysis.

Arm/Group Title Brivaracetam (POS Efficacy)
Hide Arm/Group Description:
Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Partial Onset Seizure Efficacy Set (POS Efficacy).
Overall Number of Participants Analyzed 675
Measure Type: Number
Unit of Measure: Percentage of participants
51.7
Time Frame From Entry Visit (Month 0) until the Last Visit (up to 84 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Brivaracetam (SS)
Hide Arm/Group Description Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down-Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period. Participants formed the Safety Set (SS).
All-Cause Mortality
Brivaracetam (SS)
Affected / at Risk (%)
Total   5/766 (0.65%)    
Hide Serious Adverse Events
Brivaracetam (SS)
Affected / at Risk (%) # Events
Total   140/766 (18.28%)    
Blood and lymphatic system disorders   
Haemorrhagic anaemia * 1  1/766 (0.13%)  1
Hypoplastic anaemia * 1  1/766 (0.13%)  1
Iron deficiency anaemia * 1  1/766 (0.13%)  1
Microcytic anaemia * 1  1/766 (0.13%)  1
Cardiac disorders   
Cardiac arrest * 1  2/766 (0.26%)  2
Cardiac failure * 1  2/766 (0.26%)  2
Myocardial infarction * 1  2/766 (0.26%)  2
Angina pectoris * 1  1/766 (0.13%)  1
Cardio-respiratory arrest * 1  1/766 (0.13%)  1
Coronary artery stenosis * 1  1/766 (0.13%)  1
Congenital, familial and genetic disorders   
Sickle cell anaemia * 1  1/766 (0.13%)  1
Endocrine disorders   
Goitre * 1  1/766 (0.13%)  1
Eye disorders   
Diplopia * 1  1/766 (0.13%)  1
Gastrointestinal disorders   
Abdominal pain * 1  2/766 (0.26%)  2
Inguinal hernia * 1  2/766 (0.26%)  2
Vomiting * 1  2/766 (0.26%)  2
Dysphagia * 1  1/766 (0.13%)  1
Gastritis * 1  1/766 (0.13%)  1
Oesophageal perforation * 1  1/766 (0.13%)  1
Pancreatitis * 1  1/766 (0.13%)  1
Pancreatitis acute * 1  1/766 (0.13%)  1
Small intestinal obstruction * 1  1/766 (0.13%)  1
General disorders   
Pyrexia * 1  2/766 (0.26%)  2
Asthenia * 1  1/766 (0.13%)  1
Device malfunction * 1  1/766 (0.13%)  2
Non-cardiac chest pain * 1  1/766 (0.13%)  1
Hepatobiliary disorders   
Cholelithiasis * 1  3/766 (0.39%)  3
Cholecystitis chronic * 1  1/766 (0.13%)  1
Infections and infestations   
Pneumonia * 1  5/766 (0.65%)  5
Sepsis * 1  2/766 (0.26%)  2
Appendicitis * 1  1/766 (0.13%)  1
Appendicitis perforated * 1  1/766 (0.13%)  1
Diverticulitis * 1  1/766 (0.13%)  1
Gastroenteritis escherichia coli * 1  1/766 (0.13%)  1
Infected cyst * 1  1/766 (0.13%)  1
Infection * 1  1/766 (0.13%)  1
Osteomyelitis * 1  1/766 (0.13%)  1
Otitis media chronic * 1  1/766 (0.13%)  1
Perineal abscess * 1  1/766 (0.13%)  1
Pharyngitis bacterial * 1  1/766 (0.13%)  1
Typhoid fever * 1  1/766 (0.13%)  1
Urinary tract infection * 1  1/766 (0.13%)  1
Wound infection * 1  1/766 (0.13%)  1
Injury, poisoning and procedural complications   
Toxicity to various agents * 1  3/766 (0.39%)  4
Accidental overdose * 1  2/766 (0.26%)  2
Brain contusion * 1  2/766 (0.26%)  2
Contusion * 1  2/766 (0.26%)  2
Fall * 1  2/766 (0.26%)  2
Head injury * 1  2/766 (0.26%)  2
Joint dislocation * 1  2/766 (0.26%)  2
Road traffic accident * 1  2/766 (0.26%)  2
Cervical vertebral fracture * 1  1/766 (0.13%)  1
Concussion * 1  1/766 (0.13%)  1
Craniocerebral injury * 1  1/766 (0.13%)  1
Eye injury * 1  1/766 (0.13%)  1
Foot fracture * 1  1/766 (0.13%)  1
Humerus fracture * 1  1/766 (0.13%)  1
Intentional overdose * 1  1/766 (0.13%)  1
Jaw fracture * 1  1/766 (0.13%)  1
Laceration * 1  1/766 (0.13%)  1
Limb injury * 1  1/766 (0.13%)  1
Lower limb fracture * 1  1/766 (0.13%)  1
Nail injury * 1  1/766 (0.13%)  1
Post procedural complication * 1  1/766 (0.13%)  1
Procedural pain * 1  1/766 (0.13%)  1
Pubis fracture * 1  1/766 (0.13%)  1
Radius fracture * 1  1/766 (0.13%)  1
Rib fracture * 1  1/766 (0.13%)  1
Skeletal injury * 1  1/766 (0.13%)  1
Skull fracture * 1  1/766 (0.13%)  1
Spinal compression fracture * 1  1/766 (0.13%)  1
Spinal cord injury cervical * 1  1/766 (0.13%)  1
Subdural haematoma * 1  1/766 (0.13%)  1
Tendon rupture * 1  1/766 (0.13%)  1
Thermal burn * 1  1/766 (0.13%)  1
Tibia fracture * 1  1/766 (0.13%)  1
Investigations   
Diagnostic procedure * 1  1/766 (0.13%)  1
Transaminases increased * 1  1/766 (0.13%)  1
Troponin increased * 1  1/766 (0.13%)  1
Weight decreased * 1  1/766 (0.13%)  1
Metabolism and nutrition disorders   
Hyponatraemia * 1  3/766 (0.39%)  3
Metabolic acidosis * 1  1/766 (0.13%)  1
Musculoskeletal and connective tissue disorders   
Cervical spinal stenosis * 1  2/766 (0.26%)  2
Back pain * 1  1/766 (0.13%)  1
Intervertebral disc protrusion * 1  1/766 (0.13%)  1
Osteonecrosis * 1  1/766 (0.13%)  1
Rhabdomyolysis * 1  1/766 (0.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Gliomatosis cerebri * 1  1/766 (0.13%)  1
Thymoma * 1  1/766 (0.13%)  1
Nervous system disorders   
Convulsion * 1  15/766 (1.96%)  16
Status epilepticus * 1  11/766 (1.44%)  11
Epilepsy * 1  7/766 (0.91%)  7
Seizure cluster * 1  4/766 (0.52%)  4
Headache * 1  2/766 (0.26%)  2
Ischaemic stroke * 1  2/766 (0.26%)  2
Partial seizures with secondary generalisation * 1  2/766 (0.26%)  2
Transient ischaemic attack * 1  2/766 (0.26%)  2
Ataxia * 1  1/766 (0.13%)  1
Balance disorder * 1  1/766 (0.13%)  1
Carpal tunnel syndrome * 1  1/766 (0.13%)  1
Cerebellar syndrome * 1  1/766 (0.13%)  1
Cerebrovascular accident * 1  1/766 (0.13%)  1
Cervical cord compression * 1  1/766 (0.13%)  1
Complex partial seizures * 1  1/766 (0.13%)  1
Dementia Alzheimer's type * 1  1/766 (0.13%)  1
Encephalitis * 1  1/766 (0.13%)  1
Grand mal convulsion * 1  1/766 (0.13%)  1
Hemiparesis * 1  1/766 (0.13%)  1
Hydrocephalus * 1  1/766 (0.13%)  1
Loss of consciousness * 1  1/766 (0.13%)  1
Metabolic encephalopathy * 1  1/766 (0.13%)  1
Myelopathy * 1  1/766 (0.13%)  1
Neuropathy peripheral * 1  1/766 (0.13%)  1
Polyneuropathy * 1  1/766 (0.13%)  1
Radiculopathy * 1  1/766 (0.13%)  1
Simple partial seizures * 1  1/766 (0.13%)  1
Somnolence * 1  1/766 (0.13%)  1
Pregnancy, puerperium and perinatal conditions   
Imminent abortion * 1  1/766 (0.13%)  1
Psychiatric disorders   
Suicide attempt * 1  7/766 (0.91%)  7
Suicidal ideation * 1  5/766 (0.65%)  5
Acute psychosis * 1  2/766 (0.26%)  2
Depression * 1  2/766 (0.26%)  2
Aggression * 1  1/766 (0.13%)  1
Anxiety * 1  1/766 (0.13%)  1
Anxiety disorder * 1  1/766 (0.13%)  1
Confusional state * 1  1/766 (0.13%)  1
Delirium * 1  1/766 (0.13%)  3
Delirium febrile * 1  1/766 (0.13%)  1
Emotional disorder * 1  1/766 (0.13%)  1
Renal and urinary disorders   
Nephrolithiasis * 1  1/766 (0.13%)  1
Renal colic * 1  1/766 (0.13%)  1
Reproductive system and breast disorders   
Ovarian cyst * 1  2/766 (0.26%)  2
Menometrorrhagia * 1  1/766 (0.13%)  1
Spermatic cord haemorrhage * 1  1/766 (0.13%)  1
Uterine polyp * 1  1/766 (0.13%)  1
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure * 1  1/766 (0.13%)  1
Dyspnoea exertional * 1  1/766 (0.13%)  1
Epistaxis * 1  1/766 (0.13%)  1
Hiccups * 1  1/766 (0.13%)  1
Pneumonia aspiration * 1  1/766 (0.13%)  1
Pulmonary embolism * 1  1/766 (0.13%)  1
Pulmonary oedema * 1  1/766 (0.13%)  1
Skin and subcutaneous tissue disorders   
Rash * 1  1/766 (0.13%)  1
Surgical and medical procedures   
Intervertebral disc operation * 1  1/766 (0.13%)  1
Tenodesis * 1  1/766 (0.13%)  1
1
Term from vocabulary, MedDRA15.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brivaracetam (SS)
Affected / at Risk (%) # Events
Total   421/766 (54.96%)    
General disorders   
Fatigue * 1  59/766 (7.70%)  67
Infections and infestations   
Nasopharyngitis * 1  65/766 (8.49%)  102
Upper respiratory tract infection * 1  59/766 (7.70%)  101
Urinary tract infection * 1  57/766 (7.44%)  86
Influenza * 1  40/766 (5.22%)  47
Injury, poisoning and procedural complications   
Contusion * 1  44/766 (5.74%)  71
Fall * 1  43/766 (5.61%)  60
Musculoskeletal and connective tissue disorders   
Back pain * 1  46/766 (6.01%)  59
Arthralgia * 1  41/766 (5.35%)  56
Nervous system disorders   
Headache * 1  102/766 (13.32%)  187
Dizziness * 1  100/766 (13.05%)  123
Somnolence * 1  73/766 (9.53%)  88
Psychiatric disorders   
Depression * 1  45/766 (5.87%)  53
Anxiety * 1  42/766 (5.48%)  48
1
Term from vocabulary, MedDRA15.0
*
Indicates events were collected by non-systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: +1844 599 ext 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
ClinicalTrials.gov Identifier: NCT01339559    
Other Study ID Numbers: N01379
2010-020345-27 ( EudraCT Number )
First Submitted: April 19, 2011
First Posted: April 20, 2011
Results First Submitted: April 16, 2020
Results First Posted: June 4, 2020
Last Update Posted: June 16, 2020