Clinical Trial Results:
A Multicenter, Open-label Trial to Assess the Safety and Tolerability of a Single Intravenous Loading Dose of Lacosamide Followed by Oral Lacosamide Maintenance as Adjunctive Therapy in Subjects With Partial-onset Seizures
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Summary
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EudraCT number |
2014-004378-40 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
23 Sep 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jun 2016
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First version publication date |
17 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 |
SP0925
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00655551 | ||
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, 27517
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Public contact |
Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 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 |
18 Nov 2009
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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 |
23 Sep 2009
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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 objective of this study was to evaluate the safety and tolerability of the rapid initiation of adjunctive lacosamide (LCM) via a single intravenous (iv) loading dose (iv LCM 200 mg, 300 mg, or 400 mg) and oral LCM maintenance treatment in adult subjects with partial-onset seizures.
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Protection of trial subjects |
Subject’s informed consent was obtained and documented in accordance with local regulations, ICH-GCP requirements, and the ethical principles that have their origin in the
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information was given, in a language and at a level of complexity understandable to the subject, in both oral and written form by the investigator
or designee. Each subject had the opportunity to discuss the trial and its alternatives with the investigator.
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Background therapy |
N/A | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
08 Apr 2008
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Long term follow-up planned |
No
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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: 100
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Worldwide total number of subjects |
100
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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) |
1
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Adults (18-64 years) |
99
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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 |
The SP0925 study began recruitment in April 2008. Recruitment took place in the United States. 100 participants entered the study, which concluded in September 2009. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
N/A | ||||||||||||||||||||
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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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Are arms mutually exclusive |
Yes
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Arm title
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Lacosamide (200 mg) | ||||||||||||||||||||
Arm description |
Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Lacosamide
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Investigational medicinal product code |
SPM 927
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Other name |
Vimpat
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Pharmaceutical forms |
Infusion, Coated tablet
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Single loading intravenous (iv) Lacosamide 200 mg dose administered over a 15 minute infusion duration followed by oral Lacosamide 200 mg/day (100 mg twice daily) for 6.5 days.
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Arm title
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Lacosamide (300 mg) | ||||||||||||||||||||
Arm description |
Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Lacosamide
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Investigational medicinal product code |
SPM 927
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Other name |
Vimpat
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Pharmaceutical forms |
Infusion, Coated tablet
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Single loading intravenous (iv) Lacosamide 200 mg dose administered over a 15 minute infusion duration followed by oral Lacosamide 200 mg/day (100 mg twice daily) for 6.5 days.
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Arm title
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Lacosamide (400 mg) | ||||||||||||||||||||
Arm description |
Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Lacosamide
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Investigational medicinal product code |
SPM 927
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Other name |
Vimpat
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Pharmaceutical forms |
Infusion, Coated tablet
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Single loading intravenous (iv) Lacosamide 200 mg dose administered over a 15 minute infusion duration followed by oral Lacosamide 200 mg/day (100 mg twice daily) for 6.5 days.
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Baseline characteristics reporting groups
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Reporting group title |
Lacosamide (200 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lacosamide (300 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lacosamide (400 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lacosamide (200 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | ||
Reporting group title |
Lacosamide (300 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | ||
Reporting group title |
Lacosamide (400 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | ||
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End point title |
Number of subjects with at least one adverse event during the treatment period (up to 7 days) [1] | ||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design).
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End point type |
Primary
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End point timeframe |
Treatment period (up to 7 days)
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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: The primary objective of this open-label study was to evaluate the safety and tolerability of a single iv loading dose of lacosamide in subjects aged 16 to 60 years. The purpose of the study was to provide a description of the safety profile of a single iv loading dose of lacosamide across several safety variables. Therefore no statistical comparisons were applied in this safety study. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of subjects who withdrew from the trial due to an adverse event [2] | ||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design).
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End point type |
Primary
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End point timeframe |
Entire trial period (up to 6 weeks), screening through safety follow-up period (2 weeks post last medication)
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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: The primary objective of this open-label study was to evaluate the safety and tolerability of a single iv loading dose of lacosamide in subjects aged 16 to 60 years. The purpose of the study was to provide a description of the safety profile of a single iv loading dose of lacosamide across several safety variables. Therefore no statistical comparisons were applied in this safety study. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of subjects with at least one adverse event with an onset within 4 hours of start of infusion | ||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence (eg, noxious or pathological changes) in a subject or clinical investigation subject compared with pre-existing conditions, that occurs during any period of a clinical trial including Pre-treatment, Run-In, Wash-Out, or Follow-Up Periods. An AE is defined as being independent of assumption of any causality (eg, to study or concomitant medication, primary or concomitant disease, or study design).
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End point type |
Secondary
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End point timeframe |
0-4 hours post start of the infusion
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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 |
up to 7 days
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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 (200 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 200 mg followed by 6.5 days of oral lacosamide 100 mg twice daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lacosamide (400 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 400 mg followed by 6.5 days of oral lacosamide 200 mg twice daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lacosamide (300 mg)
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Reporting group description |
Single loading dose of intravenous (iv) lacosamide 300 mg dose followed by 6.5 days of oral lacosamide 150 mg twice daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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01 Oct 2008 |
• Administrative changes including contact and title information for the Associate Clinical Program Director, the Senior Clinical Project Manager, the Clinical Trial Biostatistician, and the Associate Medical Director were incorporated in the protocol
• Current information on the Central Laboratory Services, Central Electrocardiogram Services, and Central Bioanalytical Services were included in the protocol
• Current information on the members of the DMC was incorporated
• Text was added to permit subjects withdrawing from the LCM 300 mg group or the LCM 400 mg group, due to lack of tolerability to enter the open-label extension study at a dose as low as 100 mg/day
• The exclusion criteria for heart rate and diastolic blood pressure were revised
• The plasma sample collection for LCM determination at the Early Withdrawal Visit was added to Section 6.1 of the protocol and in the Schedule of Study Procedures footnote
• Reference to pharmacogenomic analysis was removed from the protocol
• A urine drug screen at Visit 1 was not performed. All reference to the urine drug screen was removed from the protocol
• Clinical protocol text was modified to provide a realistic timeframe for ECG measurement during the iv LCM infusion which allowed for any possible future alterations by the DMC to the initial protocol-specified infusion duration of 15 minutes
• Clinical protocol text was modified to provide a more realistic and acceptable timeframe for PK plasma sample collection for clinical site personnel
• A window period of +3 days for Visit 3/Day 8 for all LCM dose groups was added to the protocol and AE reporting was added to the LCM 300 mg group and the LCM 400 mg group under Unscheduled Visit in the Schedule of Study Procedures
• Information that the brief physical examination was to be performed after dosing was added to Section 5.4 of the protocol for consistency within the protocol |
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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 | |||
