Conversion To Monotherapy With Lamictal Extended Release Tablets For Treatment Of Partial Epilepsy

Epilepsy, Partial Clinical Trial

Official title:

A Multicenter, Double-Blind, Randomized Conversion to Monotherapy Comparison of Two Doses of Lamotrigine for the Treatment of Partial Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00355082
• Other study ID #: LAM30055
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2006
• Last updated: October 30, 2014
• Start date: May 2006
• Est. completion date: November 2008

Study information

• Verified date: May 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian FederationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Epilepsy, Partial

Intervention

Drug:
• lamotrigine, 300 mg/day
300 mg/day
• lamotrigine, 250 mg/day
250 mg/day

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Capital Fefderal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Chile	GSK Investigational Site	Providencia / Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Costa Rica	GSK Investigational Site	San Jose
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Puerto Rico	GSK Investigational Site	San Juan
Puerto Rico	GSK Investigational Site	San Juan
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	St.-Petersburg
Russian Federation	GSK Investigational Site	St.-Petersburg
Russian Federation	GSK Investigational Site	St.Petersburg
Ukraine	GSK Investigational Site	Dnepropetrovsk
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Lugansk
Ukraine	GSK Investigational Site	Lviv
Ukraine	GSK Investigational Site	Odesa
Ukraine	GSK Investigational Site	Poltava
Ukraine	GSK Investigational Site	Vinnitsa
Ukraine	GSK Investigational Site	Zaporizhzhya
United States	GSK Investigational Site	Alabaster	Alabama
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Bethesda	Maryland
United States	GSK Investigational Site	Boise	Idaho
United States	GSK Investigational Site	Charleston	West Virginia
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Danbury	Connecticut
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Des Moines	Iowa
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Edison	New Jersey
United States	GSK Investigational Site	Fairfield	Connecticut
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Flossmoor	Illinois
United States	GSK Investigational Site	Glen Burnie	Maryland
United States	GSK Investigational Site	Hattiesburg	Mississippi
United States	GSK Investigational Site	Henderson	Nevada
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lawrence	New York
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Litchfield Park	Arizona
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Loxahatchee	Florida
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Midvale	Utah
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Newark	Delaware
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Pasadena	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pikesville	Maryland
United States	GSK Investigational Site	Plainview	New York
United States	GSK Investigational Site	Renton	Washington
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Santa Ana	California
United States	GSK Investigational Site	Santa Monica	California
United States	GSK Investigational Site	Sellersville	Pennsylvania
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	St. Cloud	Minnesota
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Sunrise	Florida
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Temple	Texas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Urbana	Illinois
United States	GSK Investigational Site	Vorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Costa Rica,  Korea, Republic of,  Puerto Rico,  Russian Federation,  Ukraine, 

References & Publications (2)

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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	The percentage of participants prematurely discontinuing the study was calculated as the number of participants who discontinued the study divided by the number who reached Visit 5 minus major protocol violators. The Control group is composed of data from other similar studies and is not part of this study.	From Study Visit 5 through Visit 9 of the Treatment Phase (approximately Week 7 through Week 23)	No
Secondary	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)	The percentage of participants prematurely discontinuing the study was calculated as the number of participants who discontinued the study divided by the number who had reached Visit 5 minus major protocol violators. The Control group was composed of data from other similar studies and is not part of this study.	From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)	No
Secondary	Time to Discontinuation in the Treatment Phase	Time (days) until the participant discontinued the study	From Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)	No
Secondary	Percentage of Participants Meeting Escape Criteria in the Treatment Phase	The percentage of participants meeting Escape Criteria was calculated as the number of participants who met an Escape Criterion divided by the number who had reached Visit 5 minus major protocol violators. Escape Criteria are: (1) doubling of average monthly seizure frequency; (2) doubling of the highest consecutive 2-day seizure total; (3) occurrence of a new, more severe seizure type; or (4) worsening of generalized tonic-clonic seizures.	Study Visit 5 through Visit 9 of the Treatment phase (approximately Week 7 through Week 23)	No
Secondary	Percent Change From Baseline in Weekly Seizure Frequency Between Study Visits 3 (Start of Dosing) and 9 (End of the Treatment Phase)	Change from Baseline was measured as the number of seizures at Visits 3 through 9 minus the number of seizures at Baseline. The number of partial seizures during treatment divided by the number of weeks of treatment was compared to the weekly seizure frequency during Baseline. A positive number equals a reduction in seizure frequency.	Baseline and Study Visit 3 through Visit 9 of the Treatment phase (Treatment Week 0 through Week 23)	No
Secondary	Number of Seizure-free Participants During the Last 12 Weeks of Treatment of the Treatment Phase	The number of participants who had no seizures during the treatment period was calculated. The last 12 weeks of treatment were either Weeks 11-22 or 12-23 depending on which background AED was being withdrawn	The last 12 weeks of treatment of the Treatment phase (Monotherapy phase - approximately Week 11 through Week 23)	No
Secondary	Percent Change From Baseline in the Average Seizure Frequency Measured at the End of Participation in the Continuation Phase	Change from baseline was calculated as the average seizure frequency at the end of the Continuation Phase minus the average seizure frequency at Baseline. The number of seizures during the Continuation phase divided by the number of weeks was compared to the number of seizures at Baseline. A positive number indicates a reduction in seizure frequency.	Baseline and start of Continuation phase through Week 24 or end of participation in the Continuation phase	No
Secondary	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)	Change in seizure frequency was calculated as the average seizure frequency during the Continuation Phase minus the seizure frequency at Baseline.	Baseline and entire Continuation phase (24 Weeks)	No