Clinical Trial Results:
AN OPEN-LABEL, MULTICENTER, MULTINATIONAL STUDY OF LACOSAMIDE AS FIRST ADD-ON ANTIEPILEPTIC DRUG (AED) TREATMENT IN SUBJECTS WITH PARTIAL-ONSET SEIZURES
Summary
|
|
EudraCT number |
2009-011181-28 |
Trial protocol |
ES AT FI IT PL NL BG FR GR HU PT DE CZ DK |
Global end of trial date |
09 Aug 2013
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
28 Jun 2016
|
First version publication date |
25 Jul 2015
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
SP0954
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00955357 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
UCB BIOSCIENCES, INC.
|
||
Sponsor organisation address |
8010 Arco Corporate Drive, Raleigh, United States, 27617
|
||
Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
|
||
Scientific contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
16 Sep 2013
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Aug 2013
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The objective of this study is to evaluate the efficacy and safety of oral LCM as first add-on treatment in subjects with uncontrolled partial-onset seizures with or without secondary generalization after treatment with first adequate AED monotherapy regimen, compared to subjects with uncontrolled partial-onset seizures with or without secondary generalization despite prior adequate treatment with at least 2 AEDs (concurrently or sequentially).
|
||
Protection of trial subjects |
None
|
||
Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
05 Aug 2009
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 55
|
||
Country: Number of subjects enrolled |
Turkey: 12
|
||
Country: Number of subjects enrolled |
United States: 104
|
||
Country: Number of subjects enrolled |
Austria: 1
|
||
Country: Number of subjects enrolled |
Bulgaria: 111
|
||
Country: Number of subjects enrolled |
Czech Republic: 2
|
||
Country: Number of subjects enrolled |
Denmark: 2
|
||
Country: Number of subjects enrolled |
Finland: 8
|
||
Country: Number of subjects enrolled |
France: 2
|
||
Country: Number of subjects enrolled |
Greece: 12
|
||
Country: Number of subjects enrolled |
Italy: 33
|
||
Country: Number of subjects enrolled |
Mexico: 102
|
||
Country: Number of subjects enrolled |
Romania: 7
|
||
Country: Number of subjects enrolled |
Russian Federation: 5
|
||
Worldwide total number of subjects |
456
|
||
EEA total number of subjects |
233
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
3
|
||
Adults (18-64 years) |
439
|
||
From 65 to 84 years |
14
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Recruitment details |
An estimated 656 subjects were to be enrolled in the study at approximately 130 sites in the US, Europe, and the rest of the world. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Screening details |
Overall 461 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 456 subjects were included in the Safety Set. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Period 1 title |
Study Overall (overall period)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
First Add-on | |||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | |||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lacosamide
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
Lacosamide LCM
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Vimpat
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
First Add-on: Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.
Later Add-on: Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
Later Add-on | |||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | |||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lacosamide
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
Lacosamide LCM
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Vimpat
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
First Add-on: Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.
Later Add-on: Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
First Add-on
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Later Add-on
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
First Add-on
|
||
Reporting group description |
Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid;Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | ||
Reporting group title |
Later Add-on
|
||
Reporting group description |
Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid;Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week |
|
||||||||||||||||
End point title |
The proportion of subjects who achieved 'seizure-free status' during the first 12 weeks of the Maintenance Phase [1] | |||||||||||||||
End point description |
A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time.
This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From Week 7 (end of Week 6) to end of Week 18
|
|||||||||||||||
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. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Treatment Emergent Adverse Events were collected from Screening (Week -1) until the end of the study ( up to Week 33).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Treatment Emergent Adverse Events started on/after the date of first dose and within 30 days of the date of last dose.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Later Add-on
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
First Add-on
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
06 Oct 2009 |
Protocol Amendment 1, dated 06 Oct 2009, provided the following key changes. Based on the date of the amendment, 8 subjects were enrolled globally at the time of the amendment.
• The study was conducted only in countries in which LCM was commercially available at the time of study completion; therefore, reference to the fact that LCM was to be provided according to local laws where not commercially available was removed because it was no longer applicable
• The liver function test (LFT) withdrawal criteria were revised to reflect the Sponsor’s current understanding of the safety profile of LCM based on a comprehensive review of the data from clinical studies
• The AEs of special interest were revised to reflect the Sponsor’s current understanding of the potential risks of LCM based on a comprehensive review of the data from clinical studies and commitments to regulatory agencies
• The approach to detect safety signals was clarified to reflect the Sponsor’s current practice
• Other changes made in this amendment were minor or administrative |
||
09 Jul 2010 |
Protocol Amendment 2, dated 09 Jul 2010, provided the following key changes. Based on the date of the amendment, 111 subjects were enrolled globally at the time of the amendment.
• The inclusion criteria were revised to reflect the minimum age of eligible subjects in various countries and regions of the world. In addition, the inclusion criterion for newly diagnosed subjects in the First Add-On Group was updated to clarify that subjects were taking adequate monotherapy and to define what was considered adequate monotherapy for the purpose of this study. The maximum period for the time between the epilepsy diagnosis and the Screening Visit of the First Add-On Group was extended to 24 months in order to better reflect adjunctive therapy in clinical practice
• Exclusion criteria were amended to exclude subjects with cranial surgery within the last year prior to the study. Cranial surgery indicated the presence of acute or unstable neurological disorders, which were exclusionary per protocol
• Visit windows for titration phone calls were updated to allow for a variation in time of ±1 day relative to Visit 2
• Other changes made in this amendment were minor or administrative |
||
14 Dec 2010 |
Protocol Amendment 3, dated 14 Dec 2010, was a substantial amendment and provided the following key changes. Based on the date of the amendment, 242 subjects were enrolled globally at the time of the amendment.
• An exclusion criterion was added for known sodium channelopathy. The decision to exclude subjects with known channelopathies, such as Brugada syndrome, from clinical studies with LCM was based on a Food and Drug Administration (FDA) recommendation (17 Aug 2010). The basis for this recommendation was a theoretical concern that enhanced slow inactivation of sodium channels by LCM may have been proarrhythmic in subjects with sodium channelopathies
• Revisions were made to withdrawal criteria and follow-up recommendations for abnormal LFTs based on the following:
o Newly adopted FDA Guidance for Industry on drug-induced liver injury, which went into effect in Jul 2009, and a recommendation from the FDA to reinsert previously included wording regarding additional withdrawal criteria and follow-up recommendations for abnormal LFTs in LCM protocols
o Although no new liver-related safety issues with LCM had been identified, LFT abnormal was added as a postmarketing adverse drug reaction in the LCM Company Core Data Sheet and the EU Summary of Product Characteristics; therefore, LCM protocols were amended to reflect this addition
With these revisions, liver-related safety signals continued to be detected via protocol-directed monitoring and additional follow up in ongoing and future LCM clinical studies |
||
11 Jul 2011 |
Protocol Amendment 4, dated 11 Jul 2011, was a substantial amendment and provided the following key changes. Based on the date of the amendment, 401 subjects were enrolled globally at the time of the amendment. The changes in Protocol Amendment 4 only affected subjects in the First Add-On Group because the Later Add-On Group’s enrollment was closed prior to the amendment’s approval in any of the countries.
• The Sponsor’s name was changed to UCB BIOSCIENCES, INC. Specific Sponsor contact information was updated, and the US phone numbers for reporting serious adverse events (SAEs) were revised. The name and address of the study medication supplier was updated
• Switzerland was added as a participating country, with the inclusion criterion being revised to reflect the minimum age of eligible subjects from this country
• The inclusion criterion defining the minimum allowed seizure frequency was revised to ≥3 partial-onset seizures (IA, IB, or IC) at any time during the 3 months prior to the Screening Visit from ≥1 partial-onset seizure (IA, IB, or IC) per 28 days. This change did not reflect a change in the number of seizures required in the 3 months prior to Screening, just a change in the frequency per month |
||
11 Jul 2011 |
• In addition, the inclusion criterion defining the amount of time that a subject had to be on a stable AED dose regimen and concurrent stable vagus nerve stimulation (VNS) prior to Screening was reduced from 28 days to 7 days to accommodate the First Add-On Group subjects who may have required more frequent AED dose changes in clinical practice than the Later Add-On Group subjects
• In accordance with the FDA Draft Guidance for Industry on suicidality (Suicidality: Prospective assessment of occurrence in clinical trials), which went into effect on 29 Oct 2010, the Columbia-Suicide Severity Rating Scale ([C-SSRS] Columbia University Medical Center, 2008) was added to all ongoing and new interventional protocols in order to prospectively assess the occurrence of treatment-emergent suicidality in clinical studies of drug and biological products (FDA, Draft Guidance for Industry 2010)
• A list of anticipated SAEs was included in this amendment in compliance with the FDA Guidance for Industry and Investigators on safety reporting requirements for studies conducted under an open Investigational New Drug Application (Safety reporting requirements for IND and BE/BA studies), which went into effect on 28 Mar 2011 (FDA, Guidance for Industry and Investigators, 2010)
• Other changes made in this amendment were administrative in nature |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn. |