Trial to Demonstrate the Efficacy and Safety of Conversion to Lacosamide Monotherapy for Partial-onset Seizures

Epilepsy Clinical Trial

— ALEX-MT  

Official title:

A Historical-controlled, Multicenter, Double-blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400 mg/Day Monotherapy in Subjects With Partial-onset Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00520741
• Other study ID #: SP0902
• Secondary ID: 2007-005439-27
• Status: Completed
• Phase: Phase 3
• Start date: August 2007
• Est. completion date: December 2012

Study information

• Verified date: July 2017
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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the efficacy and safety of conversion to Lacosamide monotherapy in subjects with Partial-onset Seizures who are withdrawn from 1 to 2 marketed antiepileptic drugs.

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increased risk of SUDEP in patients with only GTCS in a trial setting, the 1 remaining patient with only GTCS was withdrawn from this study.

Other known NCT identifiers

• NCT01058954

Recruitment information / eligibility

• Status: Completed
• Enrollment: 426
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Lacosamide
50 mg and 100 mg tablets provided for 200 mg twice daily dosing for up to 20 weeks.
• Lacosamide
50 mg and 100 mg tablets provided for 150 mg twice daily dosing for up to 20 weeks.

Locations

Country	Name	City	State
Australia	420	Adelaide	South Australia
Australia	421	Capmerdown	New South Wales
Australia	425	Chatswood	New South Wales
Australia	429	Clayton	Victoria
Australia	423	Herston	Queensland
Australia	422	Maroochydore	Queensland
Australia	427	Parkville	Victoria
Austria	204	Innsbruck
Canada	127	Calgary	Alberta
Canada	91	Greenfield Park	Quebec
Canada	140	Halifax	Nova Scotia
Canada	116	Hamilton	Ontario
Canada	93	London	Ontario
Canada	110	Montreal	Quebec
Canada	113	Montreal	Quebec
Denmark	223	Aarhus
Denmark	220	Copenhagen
France	402	Bron
France	404	Dijon
France	405	Ramonville Saint Agne
Germany	465	Berlin
Germany	461	Mainz
Ireland	240	Dublin
Italy	442	Bologna
Italy	449	Catanzaro
Italy	443	Ferrara
Italy	441	Milano
Italy	450	Perugia
Italy	448	Pisa
Italy	445	Reggio Calabria
Italy	447	Torrette Di Ancona
Poland	284	Czestochowa
Poland	286	Gdansk
Poland	282	Gdynia
Poland	280	Krakow
Poland	283	Lublin
Poland	290	Lublin
Poland	289	Szczecin
Poland	281	Warszawa
Poland	287	Warszawa
Puerto Rico	158	San Juan
Spain	323	Granada
Spain	324	Santa Cruz De Tenerife
United Kingdom	360	Blackpool
United Kingdom	364	London
United Kingdom	369	London
United Kingdom	361	Manchester
United Kingdom	363	Middlesborough
United Kingdom	368	Stoke on Trent
United Kingdom	367	Truro
United States	48	Alabaster	Alabama
United States	36	Albany	New York
United States	161	Alexandria	Virginia
United States	73	Ames	Iowa
United States	3	Asheville	North Carolina
United States	79	Atlanta	Georgia
United States	60	Aurora	Colorado
United States	138	Austin	Texas
United States	20	Baltimore	Maryland
United States	34	Baltimore	Maryland
United States	24	Beaufort	South Carolina
United States	19	Bethesda	Maryland
United States	10	Birmingham	Alabama
United States	58	Boise	Idaho
United States	83	Buffalo	New York
United States	72	Canton	Georgia
United States	69	Cedarhurst	New York
United States	16	Charlottesville	Virginia
United States	114	Chattanooga	Tennessee
United States	31	Chesterfield	Missouri
United States	15	Cleveland	Ohio
United States	105	Columbia	Missouri
United States	61	Columbus	Ohio
United States	111	Dallas	Texas
United States	22	Dallas	Texas
United States	41	Detroit	Michigan
United States	94	Doral	Florida
United States	133	Dover	Delaware
United States	63	Durham	North Carolina
United States	43	Edison	New Jersey
United States	46	El Paso	Texas
United States	25	Fairfield	Connecticut
United States	108	Gainesville	Florida
United States	30	Golden Valley	Minnesota
United States	100	Greensburg	Pennsylvania
United States	130	Gulf Breeze	Florida
United States	71	Hattiesburg	Mississippi
United States	131	Hines	Illinois
United States	51	Houston	Texas
United States	53	Houston	Texas
United States	18	Huntsville	Alabama
United States	78	Indianapolis	Indiana
United States	102	Jonesboro	Arkansas
United States	120	La Habra	California
United States	136	Layton	Utah
United States	17	Lebanon	New Hampshire
United States	119	Lexington	Kentucky
United States	164	Lexington	Kentucky
United States	7	Little Rock	Arkansas
United States	86	Little Rock	Arkansas
United States	156	Loma Linda	California
United States	59	Los Angeles	California
United States	76	Los Angeles	California
United States	62	Louisville	Kentucky
United States	80	Madison	Wisconsin
United States	55	Maitland	Florida
United States	124	Manhattan	Kansas
United States	8	Medford	Oregon
United States	123	Miami	Florida
United States	132	Miami	Florida
United States	28	Milwaukee	Wisconsin
United States	154	Mineola	New York
United States	1	Nashville	Tennessee
United States	122	New York	New York
United States	27	New York	New York
United States	45	Newport Beach	California
United States	42	Northport	Alabama
United States	147	Oklahoma City	Oklahoma
United States	174	Omaha	Nebraska
United States	77	Orlando	Florida
United States	49	Panama City	Florida
United States	146	Peoria	Illinois
United States	32	Philadelphia	Pennsylvania
United States	14	Phoenix	Arizona
United States	151	Phoenix	Arizona
United States	9	Phoenix	Arizona
United States	65	Pikesville	Maryland
United States	109	Pinellas Park	Florida
United States	129	Port Charlotte	Florida
United States	157	Portland	Oregon
United States	74	Renton	Washington
United States	106	Richmond	Virginia
United States	152	Rocky Mount	North Carolina
United States	66	Saint Louis	Missouri
United States	98	San Antonio	Texas
United States	21	Santa Monica	California
United States	50	Sarasota	Florida
United States	81	Sarasota	Florida
United States	40	Savannah	Georgia
United States	29	Scarborough	Maine
United States	175	Schenectady	New York
United States	11	Springfield	Illinois
United States	150	Sun City	Arizona
United States	4	Tallahassee	Florida
United States	163	Tampa	Florida
United States	26	Tarentum	Pennsylvania
United States	82	Temple	Texas
United States	2	Toledo	Ohio
United States	107	Torrance	California
United States	103	Tucson	Arizona
United States	67	Voorhees	New Jersey
United States	137	Waldorf	Maryland
United States	37	Washington	District of Columbia
United States	160	Wichita	Kansas
United States	23	Wichita	Kansas
United States	117	Wilmington	North Carolina
United States	125	Winchester	Virginia
United States	47	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  France,  Germany,  Ireland,  Italy,  Poland,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Pre-defined exit criteria: 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; 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; Occurrence of a single generalized tonic-clonic seizure if none had occurred in the 6 months prior to randomization; A prolongation or worsening of overall seizure duration, frequency, type or pattern considered by the investigator as serious enough to warrant trial discontinuation; Status epilepticus, or new onset of serial/cluster seizures	16 Weeks Maintenance Period (approximately 112 days)
Secondary	Time to First Occurrence of Any Exit Event During The Maintenance Period	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.	16 Weeks Maintenance Period (approximately 112 days)
Secondary	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	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: Met at least 1 exit criterion based on the calculations applied for the Primary Efficacy Analysis; Withdrawal due to AE with onset during the Maintenance Phase; 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.	16 Weeks Maintenance Period (approximately 112 days)
Secondary	Duration of Monotherapy Treatment During the Monotherapy Phase of The Maintenance Period (Visit 9 - Visit 12)	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.	Visit 9 - Visit 12 (approximately 10 weeks)
Secondary	Clinical Global Impression of Change (CGIC) From Baseline To Last Visit	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: Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse	Baseline; Last Visit (approximately 27 weeks)
Secondary	Patient's Global Impression of Change (PGIC) From Baseline To Last Visit	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.); Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse	Baseline; Last Visit (approximately 27 weeks)

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