Clinical trial NCT00355082: Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy
Official title: A Multicenter, Double-Blind, Randomized Conversion to Monotherapy Comparison of Two Doses of Lamotrigine for the Treatment of Partial Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy, Partial
Keywords: epilepsy
lamotrigine
Lamictal
monotherapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-07-21
Enrollment: 226
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being conducted to determine the effectiveness of a lower monotherapy dose of lamotrigine than that currently approved.

Detailed description: The study consists of a Treatment phase, where efficacy is determined and a Continuation phase for extended safety information. The Continuation phase is open to all Treatment phase participants and those who did not qualify for treatment because of an insufficient number of seizures during the Baseline phase.

Eligibility criteria: Inclusion criteria:

* Male or Female ≥13 years of age
* Have a confident diagnosis of epilepsy with partial seizures for at least 24 weeks prior to the Baseline Phase
* Have a documented history of partial seizures such that the investigator must judge that the subject is likely to have at least 4 partial seizures during the 8-week Baseline Phase.
* Have experienced at least 4 partial seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4-week (i.e., 28-day) period.
* NOTE: With prior authorization from GlaxoSmithKline (GSK), retrospective data may take the place of up to the first 4 weeks (i.e., first 28 days) of the Baseline Phase for subjects providing reliable documentation of the following:

  1. A complete daily seizure diary that includes the number, and type (i.e., simple or complex partial seizures with or without secondary generalization), of seizures experienced each day for up to 28 consecutive days immediately prior to the prospective Baseline Phase
  2. Stability of prescribed dosages of background antiepileptic drug (AED)
  3. Compliance with background AED

All subjects permitted to use retrospective baseline data must complete a minimum of four weeks (i.e., 28 days) of the prospective Baseline Phase. The retrospective plus the prospective Baseline Phases must equal the 56 consecutive days prior to the start of dosing with study drug.

* be currently receiving AED monotherapy treatment with a stable regimen of a non-enzyme inducing AED for at least four weeks prior to starting the Baseline Phase.
* be able and willing to maintain an accurate, complete, written daily seizure diary, or has a parent/caregiver who is able and willing to maintain and accurate, complete, written daily seizure diary for the entire duration of the study.
* be able to comply with the dosing of study drugs, background AED, and all study procedures.
* understand and sign written informed consent, or will have a parent or a legally authorized representative who has done so, prior to the performance of any study assessments
* if female, and of childbearing potential be using an acceptable form of birth control, to include one of the following:

  1. Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (a minimum of 2 weeks).
  2. Consistent and correct use of one of the following methods of birth control:

Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.

Any intrauterine device (IUD) with a documented failure rate of less than 1% per year

Double barrier method consisting of spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm).

NOTE: Women who have had a hysterectomy, tubal ligation, or are post-menopausal are considered to be of non-childbearing potential.

NOTE: A pharmacokinetic interaction has been observed between lamotrigine (LTG) and estrogen-based oral contraceptives. Therefore, the use of hormonal therapy (e.g., for contraception or hormone replacement therapy) is not allowed.

Exclusion criteria:

* Exhibits any primary generalized seizures (e.g., absence, myoclonic primary generalized tonic-clonic seizures).
* Has had status epilepticus within the 24 weeks prior to, or during, the Baseline Phase.
* Is taking an enzyme-inducing AED (EIAED - e.g. carbamazepine, phenytoin, phenobarbital, primidone) or is taking more than 1 background AED.
* Is currently taking lamotrigine (LTG) or has previously had an adequate trial of LTG.
* Is currently taking felbamate
* Is using hormone therapy
* Is abusing alcohol and/or other substances
* Has taken an investigational drug within the previous 30 days or plans to take an investigational drug anytime during the study.
* Is receiving chronic treatment with any medication that could influence seizure control
* NOTE: Use of benzodiazepines is allowed as specified in Section 8.1.2
* Is currently following the ketogenic diet.
* Is using vagal nerve stimulation
* Is planning surgery to control seizures during the study.
* Is pregnant, breastfeeding, or planning to become pregnant during the study or within the three weeks after the last dose of study drug.
* Is suffering from acute or progressive neurological disease, severe psychiatric disease or severe mental abnormality that is likely to interfere with the objectives of the study.
* Has any clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.

Primary outcomes:
measure: The Percentage of Participants in the 300 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase)
timeFrame: From Study Visit 5 through Visit 9 of the Treatment Phase (approximately Week 7 through Week 23)
Secondary outcomes:
measure: The Percentage of Participants in the 250 mg/Day Dose Group Who Prematurely Discontinued the Study Between Study Visit 5 (Approximately Week 7) and Visit 9 (End of the Treatment Phase)
timeFrame: From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
measure: Time to Discontinuation in the Treatment Phase
timeFrame: From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
measure: Percentage of Participants Meeting Escape Criteria in the Treatment Phase
timeFrame: Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)
measure: Percent Change From Baseline in Weekly Seizure Frequency Between Study Visits 3 (Start of Dosing) and 9 (End of the Treatment Phase)
timeFrame: Baseline and Study Visit 3 through Visit 9 of the Treatment phase (Treatment Week 0 through Week 23)
measure: Number of Seizure-free Participants During the Last 12 Weeks of Treatment of the Treatment Phase
timeFrame: The last 12 weeks of treatment of the Treatment phase (Monotherapy phase - approximately Week 11 through Week 23)
measure: Percent Change From Baseline in the Average Seizure Frequency Measured at the End of Participation in the Continuation Phase
timeFrame: Baseline and start of Continuation phase through Week 24 or end of participation in the Continuation phase
measure: The Number of Participants With at Least the Specified Change in Seizure Frequency, Compared to Baseline, at the End of Participation in the Continuation Phase (Maximum of 24 Weeks)
timeFrame: Baseline and entire Continuation phase (24 Weeks)
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: GSK Investigational Site
state: Alabama
city: Litchfield Park
country: United States
facility: GSK Investigational Site
state: Arizona
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fayetteville
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Pasadena
country: United States
facility: GSK Investigational Site
state: California
city: Santa Ana
country: United States
facility: GSK Investigational Site
state: California
city: Santa Monica
country: United States
facility: GSK Investigational Site
state: California
city: Danbury
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Fairfield
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Newark
country: United States
facility: GSK Investigational Site
state: Delaware
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Loxahatchee
country: United States
facility: GSK Investigational Site
state: Florida
city: Sunrise
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Boise
country: United States
facility: GSK Investigational Site
state: Idaho
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Flossmoor
country: United States
facility: GSK Investigational Site
state: Illinois
city: Urbana
country: United States
facility: GSK Investigational Site
state: Illinois
city: Des Moines
country: United States
facility: GSK Investigational Site
state: Iowa
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Bethesda
country: United States
facility: GSK Investigational Site
state: Maryland
city: Glen Burnie
country: United States
facility: GSK Investigational Site
state: Maryland
city: Pikesville
country: United States
facility: GSK Investigational Site
state: Maryland
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Cloud
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Hattiesburg
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Edison
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Vorhees
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Lawrence
country: United States
facility: GSK Investigational Site
state: New York
city: Plainview
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Asheville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sellersville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Temple
country: United States
facility: GSK Investigational Site
state: Texas
city: Midvale
country: United States
facility: GSK Investigational Site
state: Utah
city: Renton
country: United States
facility: GSK Investigational Site
state: Washington
city: Charleston
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Madison
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Capital Fefderal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Providencia / Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: San Jose
country: Costa Rica
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St.Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Lugansk
country: Ukraine
facility: GSK Investigational Site
city: Lviv
country: Ukraine
facility: GSK Investigational Site
city: Odesa
country: Ukraine
facility: GSK Investigational Site
city: Poltava
country: Ukraine
facility: GSK Investigational Site
city: Vinnitsa
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: French JA, Hammer AE, Vuong A, Messenheimer JA. Analysis of three lamotrigine extended-release clinical trials: comparison of pragmatic ITT and LOCF methodologies. Epilepsy Res. 2012 Aug;101(1-2):141-7. doi: 10.1016/j.eplepsyres.2012.03.015. Epub 2012 Apr 10.
citation: French JA, Temkin NR, Shneker BF, Hammer AE, Caldwell PT, Messenheimer JA. Lamotrigine XR conversion to monotherapy: first study using a historical control group. Neurotherapeutics. 2012 Jan;9(1):176-84. doi: 10.1007/s13311-011-0088-3.