Clinical Trial Results:
An open-label pilot study to assess the safety of oral lacosamide as adjunctive therapy for uncontrolled primary generalized tonic-clonic seizures in subjects
with idiopathic generalized epilepsy
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Summary
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EudraCT number |
2014-004379-22 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
30 Aug 2011
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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 |
27 Jun 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 |
SP0961
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01118949 | ||
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, 27617
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.com
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Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 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 |
11 Nov 2011
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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 |
30 Aug 2011
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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 |
The purpose of this study is to assess the safety of Lacosamide (LCM) in subjects with uncontrolled primary generalized tonic-clonic (PGTC) seizures with idiopathic generalized epilepsy (IGE).
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Protection of trial subjects |
No specific measures in the protocol to minimize pain and distress.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
17 May 2010
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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 |
14 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United States: 49
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Worldwide total number of subjects |
49
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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) |
0
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
46
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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 |
Safety Set (SS) includes all enrolled subjects who took at least 1 dose of Lacosamide (LCM). | ||||||||||||||
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Pre-assignment
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Screening details |
Participant Flow and Baseline Characteristics refer to the Safety Set (SS). | ||||||||||||||
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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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Lacosamide | ||||||||||||||
Arm description |
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lacosamide
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Investigational medicinal product code |
Lacosamide LCM
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Other name |
Vimpat
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
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Baseline characteristics reporting groups
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Reporting group title |
Lacosamide
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Reporting group description |
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lacosamide
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Reporting group description |
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week. | ||
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End point title |
Change in the number of seizure days with absence seizures from the Baseline Phase to the Maintenance Phase [1] | ||||||||||
End point description |
During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded:
• Seizure type
• Seizure frequency
A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures.
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End point type |
Primary
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End point timeframe |
From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)
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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 in tables as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Change in the number of seizure days with myoclonic seizures from the Baseline Phase to the Maintenance Phase [2] | ||||||||||
End point description |
During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded:
• Seizure type
• Seizure frequency
A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures.
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End point type |
Primary
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End point timeframe |
From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)
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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 in tables as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Changes in count of generalized spike-wave discharges on 24-hour ambulatory electroencephalogram (EEG) from Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | ||||||||||
End point description |
Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours.
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End point type |
Secondary
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End point timeframe |
From Visit 2 (Week 4) to Visit 6 (Week 8)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Changes in count of 3 Hertz (Hz) spike-wave discharges (during waking hours) on 24-hour ambulatory Electroencephalogram (EEG) from Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) | ||||||||||
End point description |
Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours.
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End point type |
Secondary
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End point timeframe |
From Visit 2 (Week 4) to Visit 6 (Week 8)
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of subjects with treatment emergent adverse events (TEAEs) during the 10-week Treatment Period | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
From Visit 2 (Week 4) to Visit 7 (Week 13)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects withdrawn from the study due to Treatment Emergent Adverse Events (TEAEs) during the 10-week Treatment Period | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
From Visit 2 (Week 4) to Visit 7 (Week 13)
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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 up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16.
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Adverse event reporting additional description |
Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of Lacosamide.
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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 |
9.1
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Reporting groups
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Reporting group title |
Lacosamide
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Reporting group description |
Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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02 Nov 2010 |
The original protocol, dated 31 Aug 2009, was amended on 02 Nov 2010; changes are described in the following subsection.
Protocol Amendment 1
Changes based on the amendment that affected SP0961 included, but were not limited to:
• Administrative changes included changes to the Sponsor Authorization and Study Contact Information for the Clinical Program Director and Clinical Trial Biostatistician
• Increased the number of study sites from 10 to 25
• Revised the inclusion criterion for number of PGTC seizures prior to Baseline to increase the duration from 28 days to 12 weeks
• Removed the inclusion criterion for number of PGTC seizures during the Baseline Phase
• Added an exclusion criterion for known sodium channelopathy, such as Brugada syndrome
• Revised withdrawal criteria and follow-up recommendations for abnormal liver function tests (LFTs)
• The primary variable of percent change in PGTC seizure frequency per 28 days from Baseline Phase to the Maintenance Phase was removed
• Clarified that the secondary variable for count of 3Hz SW discharges on 24-hour ambulatory EEG only applied to waking hours
• The term “Holter monitor” was replaced by “recording device” for the 24-hour ambulatory EEG recordings
• Urinalysis parameter acetone was changed to ketones
• “Procedures for Data Monitoring Committee” was replaced by “DMC Charter”
Based on the date of the amendment, 9 subjects were enrolled in the study prior to this amendment |
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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 | |||
