Clinical Trial Results:
An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Treatment With Levetiracetam in Japanese Patients (≥4 to <16 Years) With Uncontrolled Generalized Tonic-clonic (GTC) Seizures Despite Treatment With 1 or 2 Antiepileptic Drug(s)
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Summary
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EudraCT number |
2014-004382-25 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
04 Jun 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jun 2016
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First version publication date |
13 May 2015
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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 |
N01363
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01292837 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB Japan Co. Ltd.
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Sponsor organisation address |
8-17-1 Nishi-Shinjuku, Tokyo, Japan, 160-0023
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 4815 15, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, 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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Sep 2013
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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 |
04 Jun 2013
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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 efficacy and safety of Levetiracetam (LEV) dry syrup at doses up to 60 mg/kg/day or 3000 mg/day used as adjunctive therapy in Japanese pediatric subjects aged ≥ 4 to < 16 years with uncontrolled generalized tonic-clonic (GTC) seizures, despite treatment with 1 or 2 Antiepileptic Drugs (AEDs).
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Protection of trial subjects |
Reduced the number of laboratory test to minimise pain and distress.
The pregnancy test performed by urinalysis instead of blood biochemistry, to minimise the blood volume.
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Background therapy |
One or two antiepileptic drug(s) | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
09 Feb 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
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 |
Japan: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
0
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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) |
6
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This multicenter study started to enroll subjects in Februray 2011 in order to end up with 8 sites in Japan with enrolled subjects. Participant Flow refers to the Enrolled Set (ES). ES consists of all subjects who signed the consent form and participated in the Prospective Baseline Period. | ||||||||||||
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Pre-assignment
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Screening details |
Subjects were screened at 8 sites in Japan. Overall, 13 subjects were screened and enrolled in N01363; there were no screen failures. | ||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Levetiracetam | ||||||||||||
Arm description |
Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Levetiracetam
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Investigational medicinal product code |
ucb L059
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Other name |
EKeppra
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Pharmaceutical forms |
Powder for syrup
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Routes of administration |
Oral use
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Dosage and administration details |
The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Levetiracetam
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Reporting group description |
Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Levetiracetam
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Reporting group description |
Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks. | ||
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End point title |
The percent change from the Combined Baseline (4-week Retrospective Baseline and 4-week Prospective Baseline) in the generalized tonic-clonic seizure frequency per week over the 24-week Treatment Period (Up-Titration and Evaluation Periods) [1] | ||||||||||
End point description |
The percent change from Combined Baseline over Treatment Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Treatment Period (T) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods)
using the equation below.
The percent change from Baseline = (B - T)/B x 100
The seizure frequency per week was calculated using the following formula:
Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
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End point type |
Primary
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End point timeframe |
From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)
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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: There was no formal statistical hypothesis testing for this endpoint in this open-label, single-arm study. Results were summarized in tables as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
The percent change in generalized tonic-clonic seizure frequency per week from the Combined Baseline Period over the Evaluation Period | ||||||||||
End point description |
The percent change from Combined Baseline over Evaluation Period was calculated from the Generalized Tonic-Clonic (GTC) seizure frequency per week during the Evaluation Period (E) and during the Baseline Period (B, Combined Baseline, ie, Retrospective and Prospective Baseline Periods) using the equation below.
The percent change from Baseline = (B - E)/B x 100
The seizure frequency per week was calculated using the following formula:
Frequency per week of GTC seizures = total number of GTC seizures in the corresponding period / number of days for observation in the corresponding period x 7
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End point type |
Secondary
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End point timeframe |
From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Generalized tonic-clonic seizures 50 % responder rate (the proportion of subjects with 50 % or more reduction from the Combined Baseline in the frequency of generalized tonic-clonic seizures) during the Treatment Period | ||||||||||
End point description |
The 50 % responder rate during the Treatment Period was the proportion of subjects who reported a ≥ 50 % reduction in seizure frequency per week from Baseline during the Treatment Period.
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End point type |
Secondary
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End point timeframe |
From Baseline (Week -8) to Treatment Period (Week 0 to Week 24)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Generalized tonic-clonic seizures 50 % responder rate during the Evaluation Period | ||||||||||
End point description |
The 50 % responder rate during the Evaluation Period was the proportion of subjects who reported a ≥50 % reduction in seizure frequency per week from Baseline during the Evaluation Period.
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End point type |
Secondary
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End point timeframe |
From Baseline (Week -8) to Evaluation Period (Week 4 to Week 24)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Generalized tonic-clonic seizure freedom over the Treatment Period | ||||||||
End point description |
A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Treatment Period was considered a seizure-free subject for that period.
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End point type |
Secondary
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End point timeframe |
Treatment Period (Week 0 to Week 24)
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| No statistical analyses for this end point | |||||||||
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End point title |
Generalized tonic-clonic seizure freedom over the Evaluation Period | ||||||||
End point description |
A subject with a generalized tonic-clonic seizure frequency of 0 per week throughout the Evaluation Period was considered a seizure-free subject for that period.
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End point type |
Secondary
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End point timeframe |
Evaluation Period (Week 4 to Week 24)
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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 |
Treatment Emergent Adverse Events were reported from Baseline up to Week 30.
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Adverse event reporting additional description |
The Analysis Population refers to the Safety Set. The Safety Set was a subset of the Enrolled Set and consisted of all subjects taking at least 1 dose of the study medication.
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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 |
16.0
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Reporting groups
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Reporting group title |
Levetiracetam
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Reporting group description |
Twice daily (morning and evening) orally Levetiracetam: The initial dose is 20 mg/kg/day or 1000 mg/day, divided into two equal dose for the first two weeks, followed by 40 mg/kg/day or 2000 mg/day for two weeks. After reaching 60 mg/kg/day or 3000 mg/day, treatment will continue for 20 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Aug 2010 |
• UCB changed the number of the categories for causal relationship of AEs to the study medication to 2 from 4.
• UCB changed the standard module of the CRF so that the clinical relevance of the “laboratory abnormalities” was not recorded in the eCRF.
• Errors in writing and incorrect information were corrected.
• A new Clinical Project Manager was appointed.
• There was a need to add some drugs in the list of restricted concomitant drugs and drug brand names were deleted from the lists.
• Clarification was provided that the pregnancy test was performed at the investigational site.
• The introduction section was updated to reflect that LEV was granted the regulatory approval in Japan after the final protocol was approved. |
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28 Feb 2012 |
The primary purpose of the substantial Protocol Amendment 2 was to extend the study duration and clarify the visit window during the Baseline Period. Changes to the previous edition were required for clarification. The amendment also provided the following changes:
• Administrative information was updated.
• Two additional prohibited concomitant medications, 1 restricted concomitant medication, and 1 rescue medication, were added.
• An additional reference was added. |
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29 Jan 2013 |
The primary purpose of the substantial Protocol Amendment 3 was to extend the study duration and mention the update in approval status by the Food and Drug Administration. The amendment also provided the following changes:
• Administrative information was updated.
• One additional concomitant antiepileptic medication and 1 restricted concomitant medication were added. |
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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 | |||
