Trial to Demonstrate the Efficacy and Safety of Conversion to Lacosamide Monotherapy for Partial-onset Seizures
- Registration Number
- NCT00520741
- Lead Sponsor
- UCB BIOSCIENCES, Inc.
- Brief Summary
The objective of this historical-controlled trial is to demonstrate the efficacy and safety of conversion to Lacosamide monotherapy in subjects with Partial-onset Seizures who are withdrawn from 1 to 2 marketed antiepileptic drugs.
- Detailed Description
Sudden unexplained death in epilepsy have been reported in epilepsy patients. A causal relationship with the administration of antiepileptic drugs has not been established. The most important known risk factor for sudden unexplained death in epilepsy (SUDEP) is the occurrence and frequency of generalized tonic-clonic seizures (GTCS). Twenty-seven patients with only GTCS were enrolled in the conversion to monotherapy study. In this study, two patients with only GTCS had SUDEP. Due to the potential increased risk of SUDEP in patients with only GTCS in a trial setting, the 1 remaining patient with only GTCS was withdrawn from this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 426
- Subject has a diagnosis of Epilepsy with Simple Partial Seizures (motor component) and or Complex Partial Seizures (with or without secondary generalization)
- Must be experiencing 2 to 40 seizures per 28-day period
- Stable dose of 1 or 2 marketed antiepileptic drugs
- Second Antiepileptic Drug (AED) must be less than or equal to 50 % of the minimum recommended maintenance dose per USA product label at screening
- Subject has a history of primary generalized or unclassified seizures
- Seizure disorder primarily characterized by isolated auras
- History of status epilepticus
- Seizures that are uncountable due to clustering
- Has greater than 5 seizures/day
- Subjects taking Benzodiazepines, Phenobarbital or Primidone
- Subject has Vagus Nerve Stimulation (VNS)
- Significant medical or psychiatric condition
- History of alcohol or drug abuse
- History of Ethosuximide use, Felbamate use after 1994 or Vigabatrin use after 1997
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lacosamide 400 mg/day Lacosamide Lacosamide 400 mg/day Lacosamide 300 mg/day Lacosamide Lacosamide 300 mg/day
- Primary Outcome Measures
Name Time Method Percentage of Subjects (Using Kaplan-Meier) Who Are Identified As Meeting At Least 1 Pre-defined Exit Criteria By Day 112 Relative To The Start of Withdrawal of Background Antiepileptic Drug(s) 16 Weeks Maintenance Period (approximately 112 days) Pre-defined exit criteria:
1. A 2-fold or greater increase in average monthly (28-day) partial seizure frequency (motor and non-motor) compared to average monthly partial seizure frequency (motor and non-motor) during the Baseline Phase
2. A 2-fold or greater increase in consecutive 2-day partial seizure frequency (motor and non-motor) versus the highest consecutive 2-day partial seizure frequency (motor and non-motor) that occurred during the Baseline Phase.
Note: if the highest consecutive 2-day partial seizure frequency during the Baseline Phase is 1, a 2-day partial seizure frequency of ≥3 is required to meet this exit criterion
3. Occurrence of a single generalized tonic-clonic seizure if none had occurred in the 6 months prior to randomization
4. A prolongation or worsening of overall seizure duration, frequency, type or pattern considered by the investigator as serious enough to warrant trial discontinuation
5. Status epilepticus, or new onset of serial/cluster seizures
- Secondary Outcome Measures
Name Time Method Percentage of Subjects (Using Kaplan-Meier) Who Are Identified as Meeting at Least 1 Pre-defined Exit Criteria by Day 112, Withdrew Due to Adverse Event (AE) or Withdrew Due to Lack of Efficacy During The Maintenance Period 16 Weeks Maintenance Period (approximately 112 days) Subjects were classified as having an exit event if they experienced at least 1 of the following events during the Maintenance Phase as of Day 112:
1. Met at least 1 exit criterion based on the calculations applied for the Primary Efficacy Analysis
2. Withdrawal due to AE with onset during the Maintenance Phase
3. Withdrew prematurely due to lack of efficacy during the Maintenance Phase
The date the subject experienced the event was set to the earliest date the subject met an exit criterion or the date of the last Maintenance Phase dose for subjects not meeting an exit criterion but withdrawing due to an AE or lack of efficacy.
The secondary analysis is only conducted on the Lacosamide 400 mg/day group.Time to First Occurrence of Any Exit Event During The Maintenance Period 16 Weeks Maintenance Period (approximately 112 days) The time to first occurrence (days) of any exit event was estimated using Kaplan-Meier methods and was based on the time from the start of the Maintenance Phase to the earliest date a subject met an exit criterion. Subjects who discontinued during the Maintenance Phase due to non-exit criteria reasons or who completed the Maintenance Phase before 112 days and did not meet an exit criterion were censored as of the last Maintenance Phase dose date. Subjects completing 112 days in the Maintenance Phase were censored as of Day 112.
Duration of Monotherapy Treatment During the Monotherapy Phase of The Maintenance Period (Visit 9 - Visit 12) Visit 9 - Visit 12 (approximately 10 weeks) Days on Monotherapy Treatment were defined as the number of days during the Monotherapy Phase when the subject took Lacosamide (LCM) only (ie, the total number of days exposed to LCM during the Monotherapy Phase minus any days where a concomitant or rescue Anti-epileptic Drug (AED) was taken by the subject). The days on Monotherapy Treatment did not need to be consecutive.
Clinical Global Impression of Change (CGIC) From Baseline To Last Visit Baseline; Last Visit (approximately 27 weeks) For the assessment of the Clinical Global Impression of Change (CGIC), the investigator should provide his/her assessment of the subject's clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status. He was asked the following:Please check the number that best describes the subject's condition over the past 4 weeks compared to Baseline:
1. Very much improved
2. Much improved
3. Minimally improved
4. No change
5. Minimally worse
6. Much worse
7. Very much worsePatient's Global Impression of Change (PGIC) From Baseline To Last Visit Baseline; Last Visit (approximately 27 weeks) For the assessment of the Patient's Global Impression of Change, the subject should provide his/her assessment of his/her own clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status.The subject was asked to answer the following:
Over the past 4 weeks, how have you felt compared to before you entered this clinical trial? (Please check the number that best describes your condition.)
1. Very much improved
2. Much improved
3. Minimally improved
4. No change
5. Minimally worse
6. Much worse
7. Very much worse
Trial Locations
- Locations (158)
61
🇺🇸Columbus, Ohio, United States
32
🇺🇸Philadelphia, Pennsylvania, United States
79
🇺🇸Atlanta, Georgia, United States
58
🇺🇸Boise, Idaho, United States
31
🇺🇸Chesterfield, Missouri, United States
53
🇺🇸Houston, Texas, United States
48
🇺🇸Alabaster, Alabama, United States
18
🇺🇸Huntsville, Alabama, United States
42
🇺🇸Northport, Alabama, United States
7
🇺🇸Little Rock, Arkansas, United States
59
🇺🇸Los Angeles, California, United States
156
🇺🇸Loma Linda, California, United States
120
🇺🇸La Habra, California, United States
45
🇺🇸Newport Beach, California, United States
21
🇺🇸Santa Monica, California, United States
107
🇺🇸Torrance, California, United States
94
🇺🇸Doral, Florida, United States
108
🇺🇸Gainesville, Florida, United States
55
🇺🇸Maitland, Florida, United States
130
🇺🇸Gulf Breeze, Florida, United States
132
🇺🇸Miami, Florida, United States
123
🇺🇸Miami, Florida, United States
49
🇺🇸Panama City, Florida, United States
109
🇺🇸Pinellas Park, Florida, United States
129
🇺🇸Port Charlotte, Florida, United States
81
🇺🇸Sarasota, Florida, United States
50
🇺🇸Sarasota, Florida, United States
4
🇺🇸Tallahassee, Florida, United States
72
🇺🇸Canton, Georgia, United States
131
🇺🇸Hines, Illinois, United States
78
🇺🇸Indianapolis, Indiana, United States
11
🇺🇸Springfield, Illinois, United States
73
🇺🇸Ames, Iowa, United States
34
🇺🇸Baltimore, Maryland, United States
164
🇺🇸Lexington, Kentucky, United States
137
🇺🇸Waldorf, Maryland, United States
41
🇺🇸Detroit, Michigan, United States
30
🇺🇸Golden Valley, Minnesota, United States
66
🇺🇸Saint Louis, Missouri, United States
105
🇺🇸Columbia, Missouri, United States
17
🇺🇸Lebanon, New Hampshire, United States
36
🇺🇸Albany, New York, United States
83
🇺🇸Buffalo, New York, United States
69
🇺🇸Cedarhurst, New York, United States
122
🇺🇸New York, New York, United States
154
🇺🇸Mineola, New York, United States
27
🇺🇸New York, New York, United States
175
🇺🇸Schenectady, New York, United States
3
🇺🇸Asheville, North Carolina, United States
117
🇺🇸Wilmington, North Carolina, United States
152
🇺🇸Rocky Mount, North Carolina, United States
15
🇺🇸Cleveland, Ohio, United States
138
🇺🇸Austin, Texas, United States
8
🇺🇸Medford, Oregon, United States
2
🇺🇸Toledo, Ohio, United States
100
🇺🇸Greensburg, Pennsylvania, United States
114
🇺🇸Chattanooga, Tennessee, United States
26
🇺🇸Tarentum, Pennsylvania, United States
111
🇺🇸Dallas, Texas, United States
22
🇺🇸Dallas, Texas, United States
51
🇺🇸Houston, Texas, United States
82
🇺🇸Temple, Texas, United States
16
🇺🇸Charlottesville, Virginia, United States
136
🇺🇸Layton, Utah, United States
106
🇺🇸Richmond, Virginia, United States
161
🇺🇸Alexandria, Virginia, United States
125
🇺🇸Winchester, Virginia, United States
74
🇺🇸Renton, Washington, United States
421
🇦🇺Capmerdown, New South Wales, Australia
420
🇦🇺Adelaide, South Australia, Australia
425
🇦🇺Chatswood, New South Wales, Australia
423
🇦🇺Herston, Queensland, Australia
429
🇦🇺Clayton, Victoria, Australia
427
🇦🇺Parkville, Victoria, Australia
204
🇦🇹Innsbruck, Austria
127
🇨🇦Calgary, Alberta, Canada
116
🇨🇦Hamilton, Ontario, Canada
93
🇨🇦London, Ontario, Canada
91
🇨🇦Greenfield Park, Quebec, Canada
110
🇨🇦Montreal, Quebec, Canada
402
🇫🇷Bron, France
404
🇫🇷Dijon, France
405
🇫🇷Ramonville Saint Agne, France
465
🇩🇪Berlin, Germany
441
🇮🇹Milano, Italy
442
🇮🇹Bologna, Italy
449
🇮🇹Catanzaro, Italy
461
🇩🇪Mainz, Germany
443
🇮🇹Ferrara, Italy
450
🇮🇹Perugia, Italy
448
🇮🇹Pisa, Italy
447
🇮🇹Torrette Di Ancona, Italy
445
🇮🇹Reggio Calabria, Italy
286
🇵🇱Gdansk, Poland
283
🇵🇱Lublin, Poland
289
🇵🇱Szczecin, Poland
281
🇵🇱Warszawa, Poland
158
🇵🇷San Juan, Puerto Rico
360
🇬🇧Blackpool, United Kingdom
324
🇪🇸Santa Cruz De Tenerife, Spain
323
🇪🇸Granada, Spain
364
🇬🇧London, United Kingdom
361
🇬🇧Manchester, United Kingdom
369
🇬🇧London, United Kingdom
363
🇬🇧Middlesborough, United Kingdom
367
🇬🇧Truro, United Kingdom
368
🇬🇧Stoke on Trent, United Kingdom
40
🇺🇸Savannah, Georgia, United States
146
🇺🇸Peoria, Illinois, United States
119
🇺🇸Lexington, Kentucky, United States
20
🇺🇸Baltimore, Maryland, United States
65
🇺🇸Pikesville, Maryland, United States
290
🇵🇱Lublin, Poland
287
🇵🇱Warszawa, Poland
124
🇺🇸Manhattan, Kansas, United States
160
🇺🇸Wichita, Kansas, United States
23
🇺🇸Wichita, Kansas, United States
14
🇺🇸Phoenix, Arizona, United States
151
🇺🇸Phoenix, Arizona, United States
9
🇺🇸Phoenix, Arizona, United States
63
🇺🇸Durham, North Carolina, United States
147
🇺🇸Oklahoma City, Oklahoma, United States
1
🇺🇸Nashville, Tennessee, United States
98
🇺🇸San Antonio, Texas, United States
223
🇩🇰Aarhus, Denmark
220
🇩🇰Copenhagen, Denmark
10
🇺🇸Birmingham, Alabama, United States
157
🇺🇸Portland, Oregon, United States
76
🇺🇸Los Angeles, California, United States
46
🇺🇸El Paso, Texas, United States
422
🇦🇺Maroochydore, Queensland, Australia
71
🇺🇸Hattiesburg, Mississippi, United States
284
🇵🇱Czestochowa, Poland
282
🇵🇱Gdynia, Poland
174
🇺🇸Omaha, Nebraska, United States
280
🇵🇱Krakow, Poland
67
🇺🇸Voorhees, New Jersey, United States
103
🇺🇸Tucson, Arizona, United States
86
🇺🇸Little Rock, Arkansas, United States
102
🇺🇸Jonesboro, Arkansas, United States
133
🇺🇸Dover, Delaware, United States
113
🇨🇦Montreal, Quebec, Canada
43
🇺🇸Edison, New Jersey, United States
37
🇺🇸Washington, District of Columbia, United States
29
🇺🇸Scarborough, Maine, United States
240
🇮🇪Dublin, Ireland
24
🇺🇸Beaufort, South Carolina, United States
150
🇺🇸Sun City, Arizona, United States
140
🇨🇦Halifax, Nova Scotia, Canada
25
🇺🇸Fairfield, Connecticut, United States
163
🇺🇸Tampa, Florida, United States
60
🇺🇸Aurora, Colorado, United States
77
🇺🇸Orlando, Florida, United States
62
🇺🇸Louisville, Kentucky, United States
19
🇺🇸Bethesda, Maryland, United States
47
🇺🇸Winston-Salem, North Carolina, United States
28
🇺🇸Milwaukee, Wisconsin, United States
80
🇺🇸Madison, Wisconsin, United States