Clinical Trial Results:
An open-label, multinational, multicenter, follow-up study to evaluate the long-term safety and efficacy of brivaracetam used at a flexible dose up to a maximum of 200 mg/day in subjects aged 16 years or older suffering from epilepsy.
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Summary
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EudraCT number |
2008-001433-98 |
Trial protocol |
BE CZ SE ES FR HU FI IT DE |
Global end of trial date |
20 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Apr 2018
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First version publication date |
05 Apr 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
N01315
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00761774 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB Biosciences, Inc
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Sponsor organisation address |
8010 Arco Corporate Drive, Raleigh, United States, NC 27617
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Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jul 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the long-term safety and tolerability of Brivaracetam (BRV) at individualized doses with a maximum of 200 mg/day in subjects suffering from epilepsy.
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Protection of trial subjects |
During the conduct of the study all subjects were closely monitored.
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
19 Nov 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 7
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
Czech Republic: 10
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Hungary: 4
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Sweden: 10
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Country: Number of subjects enrolled |
United States: 43
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Worldwide total number of subjects |
108
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EEA total number of subjects |
52
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
103
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
The study started to enroll patients in November 2008 and concluded in March 2017. | ||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participant Flow refers to the Safety Set, which consisted of all subjects who took at least 1 dose of study drug. | ||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||
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Arms
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Arm title
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Brivaracetam | ||||||||||||||||||||||||||||||||||||
Arm description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Brivaracetam
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Investigational medicinal product code |
BRV
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Personalized daily doses of the investigational product (IP) Brivaracetam (BRV) were divided into 2 equal intakes (morning and evening). The suggested individual starting dose of each subject was 100 mg/day. Up- and down-titration could be made by increments of a maximum 50 mg/day on a weekly basis and up to a maximum dose of 200 mg/day.
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Baseline characteristics reporting groups
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Reporting group title |
Brivaracetam
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Reporting group description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Brivaracetam
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Reporting group description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day. | ||
Subject analysis set title |
Brivaracetam (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
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Subject analysis set title |
Brivaracetam (ES)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
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End point title |
Percentage of subjects with at least one Treatment-emergent Adverse Event (TEAE) during the Evaluation Period from Entry Visit 1 through End of Treatment (up to 9 years) [1] | ||||||||||
End point description |
Treatment-emergent Adverse events (TEAE) are any untoward medical occurrences in a subject during administered study treatment, whether or not these events are related to study treatment.
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End point type |
Primary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of subjects who withdrew due to Adverse Event (AE) during the Evaluation Period from Entry Visit 1 through End of Treatment (up to 9 years) [2] | ||||||||||
End point description |
Adverse Events (AE) are any untoward medical occurrences in a subject during administered study treatment, whether or not these events are related to study treatment.
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End point type |
Primary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of subjects with a Serious Adverse Event (SAE) during the Evaluation Period from Entry Visit 1 through End of Treatment (up to 9 years) [3] | ||||||||||
End point description |
An SAE was any untoward medical occurrence that, at any dose resulted in death, was life threatening, required in-subject hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
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End point type |
Primary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of subjects on continuous Brivaracetam monotherapy for at least 3 months of the Evaluation Period (up to 9 years) | ||||||||||
End point description |
BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.
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End point type |
Secondary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of subjects on continuous Brivaracetam monotherapy for at least 6 months, of the Evaluation Period (up to 9 years) | ||||||||||
End point description |
BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.
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End point type |
Secondary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of subjects on continuous Brivaracetam monotherapy for at least 12 months of the Evaluation Period (up to 9 years) | ||||||||||
End point description |
BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.
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End point type |
Secondary
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End point timeframe |
During the Evaluation Period (up to 9 years)
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected throughout the study (up to 9 years).
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Brivaracetam (SS)
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Reporting group description |
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Jun 2010 |
Updated the protocol with regard to 5 areas:
- Study personnel and contact details
- Duration of the study and duration of participation were amended due to termination of the N01276 and N01306 studies
- Typographical and spelling errors were corrected
- Details concerning the Phase 3 partial onset seizures (POS) and Unverricht-Lundborg Disease (ULD) studies as those studies had completed since the start of this study
- Further instruction was given with regard to visit windows |
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02 Aug 2011 |
- Increased maximum dose of BRV to 200 mg/day (instead of 150 mg/day)
- Reduced the number of assessments for the subjects
- Updated procedures for reporting serious adverse events (SAEs) to implement the Food and Drug
Administration (FDA) Final Rule requirements
- Added Columbia-Suicide Severity Rating Scale (C-SSRS) to address the requirement of the FDA that prospective assessments for suicidality should be included in clinical studies involving all drugs for neurological indications
- Updated information on laboratory assessments, statistical analyses, and contact information
- Further (minor) changes were made throughout the protocol for consistency between BRV studies |
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25 Mar 2015 |
- Study personnel and contact details were updated
- The ability of the Sponsor to sign electronically was added
- Outdated safety information was removed
- Protocol language was updated to include the possibility of a named patient or compassionate use program (or similar) as a reason for ending the study duration
- Language was revised regarding Investigator deviation from the protocol in the event of a medical emergency to align with the current UCB language |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
