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Open-label Extension Study of the Phase 3 VRX-RET-E22-301 Double-Blind Trial

Primary Purpose

Epilepsy

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ezogabine: USAN Retigabine (International Nonproprietary Name)

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy, Partial Seizures, Potassium Channels, Anticonvulsant, Complex Partial Seizures, Epilepsies, Partial, RTG115098

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient has successfully completed the Maintenance and Transition phases of Study VRX-RET-E22-301 for the treatment of partial-onset seizures Patient is expected to benefit from participation in the study in the opinion of the Investigator. Exclusion Criteria: Patient meets any of the withdrawal criteria in the previous VRX-RET-E22-301 study or is experiencing an ongoing serious adverse event. Patient is receiving any investigational drug or using any experimental device in addition to Retigabine for treatment of epilepsy or any other medical condition. Patient has any other condition that would prevent compliance with the study procedures or proper reporting of adverse events.

Sites / Locations

University of Alabama -- Department of Neurology/Epilepsy Center
North Alabama Neuroscience Research Associates
Neurology Clinic
Barrow Neurological Institute
Clinical Trials Inc.
UCSD Thornton Hospital
University of Southern California -- Keck School of Medicine
West Los Angeles VA Healthcare Center
Delta Waves
University of Colorado Department Of Neurology
University of Florida -- Shands Jacksonville
University of Miami
Lovelace Scientific Resources
McFarland Clinic
University of Kentucky
Mid-Atlantic Epilepsy and Sleep Center
Henry Ford Hospital
Minnesota Epilepsy Group, P.A.
The Comprehensive Epilepsy Care Center for Children and Adults
Beth Israel Medical Center
Asheville Neurology Specialists
Medical University of Ohio at Toledo
Oregon Neurology PC
Milton S. Hershey Medical Center
Vanderbilt University Medical Center
Medical City Dallas Hospital
Neurological Clinic of Texas
Memorial Hermann Hospital
University of Virginia Comprehensive Epilepsy Program
Virginia Commonwealth University Medical Center
Hospital Italiano de Buenos Aires
Hospital General de Agudos "Dr. J.M. Ramos Mejia"
Hospital General de Agudos "Dr. Teodoro Alvarez"
Fundacion Lennox
Sanatorio del Salvador II
Hospital Privado Centro Medico de Cordoba
Hospital Universitario Prof Edgard Santos -- UFBA
Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
Hospital das Clinicas da Fac de Medicina de Sao Paulo
Foothills Medical Center
Glenrose Rehabilitation Center
Health Sciences Centre
CHUM -- Hôpital Notre-Dame
Instituto Nacional de Neurologia y Neurocirugia
Centro Medico
Hospital de Psiquiatria San Fernando, IMSS
CIF BIOTEC, Medica Sur
Antiguo Hospital Civil de Guadalajara
Hospital y Clinica OCA S.A. de C.V.
Hospital Central Dr. Ignacio Morones Prieto

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ezogabine: USAN Retigabine (International Nonproprietary Name)

Arm Description

Film-coated tablets - 50mg, 100mg or 300mg

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Serious Adverse Event (SAE) and Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization (unplanned hospital stay) or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect. Treatment-emergent AE was defined as an AE with an onset on or after the day of first dose of the study medication and on or before 30 days after the last dose date. AEs reported during parent study and worsened after first dose of RTG in this OLE study were also reported.

Number of Participants With Treatment-emergent Adverse Events Leading to Withdrawal From Study Drug

Treatment-emergent AE was defined as an AE with an onset on or after the day of first dose of the study medication and on or before 30 days after the last dose date. AEs reported during parent study and worsened after first dose of RTG in this OLE study were also reported.

Kaplan-Meier Estimate of the Probability of Discontinuation (d/c) From Study Drug

The time frame of premature study discontinuation was defined as the time from the day of first the study medication to the time of withdrawal from study drug. For those who have a taper dose start date, the time of withdrawal was the day before the start of taper dose. For those without a taper dose start date, the time of withdrawal was the last dose date. Participants who switched to the commercial product were censored at the last dose of study drug in the Kaplan-Meier analysis. All participants who withdrew from study drug prematurely but didn't switch to commercial product were counted as "events". Kaplan-Meier estimate of the probability of discontinuation at the specified time or earlier. Number of Participants continuing on RTG at each time of withdrawal were analyzed (represented as n=X in category title).

Change From Baseline in Blood Pressure

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was obtained in supine (Su) position and again in standing (St) position after the participant was standing for approximately 2 minutes at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Not Applicable (NA) indicates that data were not available.

Change From Baseline in Heart Rate

Heart rate (HR) was measured in supine (Su) position and again in standing (St) position after the participant was standing for approximately 2 minutes at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Body Temperature

Body temperature was measured in degree Celsius at each study visit (Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available

Change From Baseline in Weight

Weight was measured in ordinary indoor clothing (without shoes) and was recorded at each study visit (On Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameters-PR Interval, QRS Duration, Uncorrected QT (uQT) Interval, Corrected QT (Bazett's Correction) Interval (QTcB), Corrected QT (Friedericia's Correction) Interval (QTcF)

A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. The following electrocardiogram parameters are presented PR Interval, QRS Duration, Uncorrected QT interval (uQT), Corrected QT (Bazett's correction) interval (QTcB), Corrected QT (Friedericia's correction) interval (QTcF). Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameter-RR Interval

A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. The following electrocardiogram parameters are presented: RR Interval. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Electrocardiogram (ECG) Parameter-QRS Axis

A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. ECG parameter QRS Axis is presented here. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Hematology Parameters- Bands, Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets, White Blood Cells Count (WBC)

Following hematology parameters were assessed, Bands (Band neutrophils), Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets and WBC. Hematology parameters were assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Hematology Parameter-Red Blood Cell Count

Red Blood Cell count (RBC) was assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available..

Change From Baseline in Haematocrit

Haematocrit was assessed at Month 1, Month 2, Month 3, Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Haemoglobin

Haemoglobin was assessed at Month 1, Month 2, Month 3, , Month 6, Month 8, Month 9, Month 10, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available..

Change From Baseline in Chemistry Parameters-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)

Alkaline phosphatase (AP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Chemistry Parameters-Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium, Urea

Bicarbonate (Bic.), BUN, Calcium (Ca), Chloride (Cl), Cholesterol (Cho.), Non-fasting glucose (NFG), Phosphorus (P), Potassium (Ka), Sodium (Na), Urea were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Chemistry Parameters -Creatinine, Total Bilirubin (TB), Uric Acid (UA)

Creatinine, Total bilirubin (TB), Uric acid (UA) were assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Chemistry Parameter-Total Protein

Total Protein (TP) was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

Change From Baseline in Urine Specific Gravity

Urine Specific gravity (USG) was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Urine Power of Hydrogen (pH)

Urine pH was assessed at Month 1, Month 3, , Month 6, Month 9, Month 12 and every 4 months after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available.

Change From Baseline in Post-void Residual Bladder Ultrasound Volume

Post-void residual (PVR) bladder was assessed using ultrasound scan to assess urinary retention at Month 1, Month 3, Month 12 and annually after Month 12. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

Change From Baseline in Overall American Urological Association (AUA) Symptom Index Score

An AUA Symptom Index is a 7-item Likert-scored scale describing urinary bladder function and was completed by the Investigator to assess the participant's urinary voiding function at Month 1, Month 3, Month 12 and annually after Month 12. The index scale ranges from 0-35, where higher scores are indicative of a worse issue. Scores are categorized as 0-7 mild, 8-19 moderate and >19 severe. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

Number of Participants With Abnormal Results in Physical Examination

A complete physical examination was performed at the end of each 12 month study cycle. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). If a participant had an abnormal result for at least one body system of exam, that participant was included in the 'Abnormal' category

Number of Participants With Abnormal Results of Neurological Examination

Participants were assessed at Month 1, Month 3, Month 6, Month 9, Month 12 and every 4 months after Month 12. Participants in the worst category among the results of all neurological examination parameters are presented. Abnormal results were categorised as Abnormal not Clinically Significant (AbNCS)and Abnormal and Clinically Significant (AbCS). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

Number of Participants With Pigmentation of Non-retinal Ocular Tissue

The ophthalmologist/retina specialist determined the presence or absence of abnormal discoloration of all non-retinal ocular tissues. Only those participants available at the specified time points were analyzed.

Number of Participants With Pigmentation of Retinal Ocular Tissue

The ophthalmologist/retina specialist determined the presence or absence of abnormal discoloration of retinal ocular tissues. It included Pigmentary abnormalities in the macula, of peripheral retina as well as in both of them.. Only those participants available at the specified time points were analyzed.

Number of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa

An assessment of the participant's nails, lips, skin and mucosa was completed by the investigator at the 4 monthly study visits. The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids,lips, nails, and mucosa

Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination

A comprehensive eye examination was conducted by retina specialist or general ophthalmologist to assess best corrected visual acuity. An initial comprehensive eye examination was completed by an ophthalmologist for all participants. This exam was not associated with a specific visit. Thereafter, eye examinations was performed approximately every 6 months. Eye examination was introduced following protocol amendment and was conducted in all participants. Participants discontinued before implementation of this amendment and who have not had a comprehensive eye examination and skin examination (and follow-up by a dermatologist, if clinically indicated) were asked to return to the clinic for an evaluation of their skin (and follow-up dermatology examination, if clinically indicated) and for a comprehensive eye examination. Number of Par. with both initial and at least one follow-up exam while on RTG treatment were analyzed.

Number of Participants With a Decrease in Confrontational Visual Field From Initial Examination

Decrease in confrontation visual field is defined as a participant having a normal initial exam and an abnormal exam thereafter or, a response of clinically significant worsening in either eye since the last assessment.

Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine

The ophthalmologist/retina specialist determined the presence or absence of retinal and non-retinal ocular abnormalities. Retinal abnormalities included abnormalities in the macula and/or the peripheral retina and non-retinal ocular pigmentary abnormality.

Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine

An assessment of the participant's nails, lips, skin and mucosa was completed by the investigator at the 6 monthly SFUCP study visits. The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa.

Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

Retinal pigmentary abnormality was determined by either an ophthalmologist or retina specialist. Retinal pigmentary abnormality included pigmentary abnormality of macula, pigmentary abnormality of the peripheral retina and non-retinal ocular pigmentary abnormality. If a participant had pigmentary abnormality of macula and pigmentary abnormality of the peripheral retina both should be resolved in order for retinal pigmentary abnormality to be considered resolved. If a participant had non-retinal ocular pigmentary abnormality in more than location (conjunctiva, sclera, cornea, iris or lens), all should be resolved for non-retinal pigmentary abnormality to be considered resolved. Only participants with resolution of the specified pigmentation are included in this analysis.

Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

Assessments were at approximately 6-monthly intervals (timed relative to the participants previous dermatology assessment) until the abnormal discoloration either resolved or stabilized (as defined by no changes over 2 consecutive 6-monthly assessments performed by the dermatologist over at least 12 months after discontinuation of retigabine). The assessment of the participant's skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa. Only participants with resolution of the specified tissue are included in this analysis.

Secondary Outcome Measures

Percentage Change From Baseline in the 28-day Partial Seizure

Twenty-eight-day total partial seizure frequency during the study is defined as the sum of total partial seizures from First date (Baseline visit date +1 if no seizures on Baseline or Baseline visit date if seizures reported on the Baseline) to Last date (last visit date for seizure record with non-missing response), divided by applicable days, standardized by 28 days. The applicable days are the days in which the subject had non-missing seizure data. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed.

Number of Responders

A participant was classified as a responder if there is an at least 50% reduction from Baseline in the 28-day total Partial Seizure frequency. Baseline was defined as the parent study Baseline. Only those participants available at the specified time points were analyzed.

Number of Participants Who Were Seizure Free for Any 6 Continuous Months

Number of seizure free days is defined as the number of applicable days without any seizures (partial, generalized or unclassified). Only the days in which a subject had non-missing seizure data were considered as applicable days. Duration of exposure is defined using a window range allowed for each scheduled visit. At least 6 months of exposure is defined as >= 173 days of exposure since the window range for Month 6 visit is +/- 7 days. Only those participants available at the specified time points were analyzed.

Number of Participants Who Were Seizure Free for Any 12 Continuous Months

Duration of exposure is defined using a window range allowed for each scheduled visit. At least 12 months of exposure is defined as >= 353 days of exposure since the window range for Month 12 visit is +/- 7 days. Only those participants available at the specified time points were analyzed.

Percentage of Seizure-free Days

Number of seizure free days is defined as the number of applicable days without any seizures (partial, generalized or unclassified). Only the days in which a participant had non-missing seizure data was considered as applicable days

Change From Baseline in Quality of Life in Epilepsy (QOLIE)-31-P Questionnaire

The QOLIE-31-P (Version 2.0) was utilized to assess quality of life. The QOLIE-31-P assessment was completed by the participants at Baseline, Month 3, Month 6, Month 9, Month 12 and annually after Month 12. The QOLIE has 7 sub scales as energy fatigue, emotional well being, social functioning, cognitive, medication effects, seizure worry and overall QOL. The assessment range for the overall score and the sub-scales is 0-100, where higher scores indicate greater well being. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

Full Information

NCT ID

NCT00310375

First Posted

March 30, 2006

Last Updated

July 14, 2020

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00310375

Brief Title

Open-label Extension Study of the Phase 3 VRX-RET-E22-301 Double-Blind Trial

Official Title

A Multicenter, Open-label, Long-term, Safety, Tolerability and Efficacy Study of Retigabine in Adult Epilepsy Patients With Partial-onset Seizures (Extension of Study VRX-RET-E22-301)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

May 1, 2006 (Actual)

Primary Completion Date

November 30, 2016 (Actual)

Study Completion Date

March 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures, who completed the VRX-RET-E22-301 double-blind study. The efficacy of long-term treatment with retigabine and patient quality of life will also be assessed.

Detailed Description

This Phase 3 trial is an open-label extension study of the placebo-controlled, double-blind VRX-RET-E22-301 trial. Patients who have completed the VRX-RET-E22-301 trial and who meet inclusion and exclusion criteria will be treated with 600-1200 mg/day of retigabine as an adjunct therapy to their current antiepileptic drugs (AEDs) or vagal nerve stimulation. Treatment will be continued until retigabine is commercially available, or until the program is discontinued. Patients will be recruited from 45-50 sites in the United States, Canada, Mexico, Brazil, and Argentina. The safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures will be evaluated. In addition, the efficacy of long-term treatment with retigabine and patient quality of life will be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

Epilepsy, Partial Seizures, Potassium Channels, Anticonvulsant, Complex Partial Seizures, Epilepsies, Partial, RTG115098

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

181 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ezogabine: USAN Retigabine (International Nonproprietary Name)

Arm Type

Experimental

Arm Description

Film-coated tablets - 50mg, 100mg or 300mg

Intervention Type

Drug

Intervention Name(s)

Ezogabine: USAN Retigabine (International Nonproprietary Name)

Other Intervention Name(s)

GKE-841, D-23129, GW582892X

Intervention Description

Film-coated tablets containing 50 mg, 100 mg, or 300 mg of retigabine per tablet. Dosage and frequency will be specific to each patient so long as the patient receives between 600 and 1200 mg of retigabine per day. The duration will be until the trial concludes or the patient leaves the trial.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-emergent Serious Adverse Event (SAE) and Adverse Event (AE)

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With Treatment-emergent Adverse Events Leading to Withdrawal From Study Drug

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Kaplan-Meier Estimate of the Probability of Discontinuation (d/c) From Study Drug

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Change From Baseline in Blood Pressure

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Heart Rate

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Body Temperature

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Weight

Description

Time Frame

Baseline and Up to Month 108

Title

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in the 12-lead Electrocardiogram (ECG) Parameter-RR Interval

Description

A 12-lead ECG was performed at each study visit during the first year of the study (Month 1, Month 3, Month 6, Month 9, Month 12) and annually after one year. The following electrocardiogram parameters are presented: RR Interval. Baseline assessment in this study is defined as the last assessment for the endpoint in parent study taken prior to the first active treatment with Retigabine. Change from Baseline was calculated as post-Baseline value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Electrocardiogram (ECG) Parameter-QRS Axis

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Hematology Parameters- Bands, Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets, White Blood Cells Count (WBC)

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Hematology Parameter-Red Blood Cell Count

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Haematocrit

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Haemoglobin

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Chemistry Parameters-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Chemistry Parameters-Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium, Urea

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Chemistry Parameters -Creatinine, Total Bilirubin (TB), Uric Acid (UA)

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Chemistry Parameter-Total Protein

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Urine Specific Gravity

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Urine Power of Hydrogen (pH)

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Post-void Residual Bladder Ultrasound Volume

Description

Time Frame

Baseline and Up to Month 108

Title

Change From Baseline in Overall American Urological Association (AUA) Symptom Index Score

Description

Time Frame

Baseline and Up to Month 108

Title

Number of Participants With Abnormal Results in Physical Examination

Description

Time Frame

Up to Month 108

Title

Number of Participants With Abnormal Results of Neurological Examination

Description

Time Frame

Up to Month 108

Title

Number of Participants With Pigmentation of Non-retinal Ocular Tissue

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With Pigmentation of Retinal Ocular Tissue

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With a Decrease in Confrontational Visual Field From Initial Examination

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine

Description

Time Frame

2 years and 9 months

Title

Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine

Description

Time Frame

2 years 9 months

Title

Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

Description

Time Frame

2 years 9 months

Title

Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

Description

Time Frame

2 years 9 months

Secondary Outcome Measure Information:

Title

Percentage Change From Baseline in the 28-day Partial Seizure

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Responders

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants Who Were Seizure Free for Any 6 Continuous Months

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Number of Participants Who Were Seizure Free for Any 12 Continuous Months

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Percentage of Seizure-free Days

Description

Time Frame

Assessed up to a maximum of 9 years

Title

Change From Baseline in Quality of Life in Epilepsy (QOLIE)-31-P Questionnaire

Description

Time Frame

Assessed up to a maximum of 9 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

University of Alabama -- Department of Neurology/Epilepsy Center

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

North Alabama Neuroscience Research Associates

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35801

Country

United States

Facility Name

Neurology Clinic

City

Northport

State/Province

Alabama

ZIP/Postal Code

35476

Country

United States

Facility Name

Barrow Neurological Institute

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85013

Country

United States

Facility Name

Clinical Trials Inc.

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

UCSD Thornton Hospital

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

University of Southern California -- Keck School of Medicine

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

West Los Angeles VA Healthcare Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90073

Country

United States

Facility Name

Delta Waves

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80918

Country

United States

Facility Name

University of Colorado Department Of Neurology

City

Denver

State/Province

Colorado

ZIP/Postal Code

80010

Country

United States

Facility Name

University of Florida -- Shands Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Lovelace Scientific Resources

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34233

Country

United States

Facility Name

McFarland Clinic

City

Ames

State/Province

Iowa

ZIP/Postal Code

50010

Country

United States

Facility Name

University of Kentucky

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536

Country

United States

Facility Name

Mid-Atlantic Epilepsy and Sleep Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20817

Country

United States

Facility Name

Henry Ford Hospital

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Minnesota Epilepsy Group, P.A.

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55102

Country

United States

Facility Name

The Comprehensive Epilepsy Care Center for Children and Adults

City

Chesterfield

State/Province

Missouri

ZIP/Postal Code

63017

Country

United States

Facility Name

Beth Israel Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

Facility Name

Asheville Neurology Specialists

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28801

Country

United States

Facility Name

Medical University of Ohio at Toledo

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43614

Country

United States

Facility Name

Oregon Neurology PC

City

Tualatin

State/Province

Oregon

ZIP/Postal Code

97062

Country

United States

Facility Name

Milton S. Hershey Medical Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37212

Country

United States

Facility Name

Medical City Dallas Hospital

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

Neurological Clinic of Texas

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

Memorial Hermann Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

University of Virginia Comprehensive Epilepsy Program

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

Facility Name

Virginia Commonwealth University Medical Center

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

Facility Name

Hospital Italiano de Buenos Aires

City

Capital Federal

State/Province

CBA

ZIP/Postal Code

C1181ACH

Country

Argentina

Facility Name

Hospital General de Agudos "Dr. J.M. Ramos Mejia"

City

Capital Federal

State/Province

CBA

Country

Argentina

Facility Name

Hospital General de Agudos "Dr. Teodoro Alvarez"

City

Capital Federal

State/Province

CBA

Country

Argentina

Facility Name

Fundacion Lennox

City

Cordoba

State/Province

CRD

ZIP/Postal Code

5000

Country

Argentina

Facility Name

Sanatorio del Salvador II

City

Cordoba

State/Province

CRD

ZIP/Postal Code

5000

Country

Argentina

Facility Name

Hospital Privado Centro Medico de Cordoba

City

Cordoba

State/Province

CRD

ZIP/Postal Code

X5016KEH

Country

Argentina

Facility Name

Hospital Universitario Prof Edgard Santos -- UFBA

City

Salvador

State/Province

ZIP/Postal Code

40110-060

Country

Brazil

Facility Name

Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia

City

Ribeirao Preto

State/Province

ZIP/Postal Code

14048-900

Country

Brazil

Facility Name

Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP

City

Sao Paulo

State/Province

ZIP/Postal Code

04024 002

Country

Brazil

Facility Name

Hospital das Clinicas da Fac de Medicina de Sao Paulo

City

Sao Paulo

State/Province

ZIP/Postal Code

05403-900

Country

Brazil

Facility Name

Foothills Medical Center

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2N 2T9

Country

Canada

Facility Name

Glenrose Rehabilitation Center

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T5G 0B7

Country

Canada

Facility Name

Health Sciences Centre

City

St. John's

State/Province

Newfoundland and Labrador

ZIP/Postal Code

A1B 3V6

Country

Canada

Facility Name

CHUM -- Hôpital Notre-Dame

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H2L 4M1

Country

Canada

Facility Name

Instituto Nacional de Neurologia y Neurocirugia

City

La Fama

State/Province

ZIP/Postal Code

42690

Country

Mexico

Facility Name

Centro Medico

City

Mexico

State/Province

ZIP/Postal Code

03229

Country

Mexico

Facility Name

Hospital de Psiquiatria San Fernando, IMSS

City

Mexico

State/Province

ZIP/Postal Code

14050

Country

Mexico

Facility Name

CIF BIOTEC, Medica Sur

City

Tlalpan

State/Province

ZIP/Postal Code

14050

Country

Mexico

Facility Name

Antiguo Hospital Civil de Guadalajara

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44280

Country

Mexico

Facility Name

Hospital y Clinica OCA S.A. de C.V.

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64000

Country

Mexico

Facility Name

Hospital Central Dr. Ignacio Morones Prieto

City

San Luis Potosi

State/Province

SLP

ZIP/Postal Code

78250

Country

Mexico

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD is available via the Clinical Study Data Request site (click on the link provided below)

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

https://clinicalstudydatarequest.com/Posting.aspx?ID=20375

Learn more about this trial

Open-label Extension Study of the Phase 3 VRX-RET-E22-301 Double-Blind Trial

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