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Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097

Primary Purpose

Epilepsy

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Retigabine (INN), Ezogabine (USAN)

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Partial Seizures, Epilepsy, RTG115097, Complex Partial Seizures, Anticonvulsant, Potassium Channels, Epilepsies, Partial

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-E22-302 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-E22-302 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

Institute of Clniical Neurosciences
North Coast Neurology Centre
Flinders Medical Centre
Royal Melbourne Hospital
Austin & Repatriation Medical Centre
General Hospital Middelheim -- Department of Neurology
AZ Sint-Jan
Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
Centre Neurologique William Lennox
Hopital Civil de Steasbourg Clinique Neurologie
Hopital Neurologique Pierre Wertheimer
CHU Pontchaillou
Centre Medical de La Teppe
Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
Universitaet Giessen / Marburg Neurologie
Universitaetsklinik Mainz Neurologische Klinik
University of Bonn -- Department for Epileptplogy
Private Neurologische Paraxis
Universitaetslinkum Ulm Poliklinik fuer Neurologie
Pecs University of Science, Clinic of Neurology
Orszagos Pszichiatriai es Neurologiai Intezet
Orszagos Idegsebeszeti Tudomanyos Intezet
Assaf Harofeh Medical Center
Rambam Medical Center
Wolfson Medical Center
Western Galilee Hospital
Chaim Sheba Medical Center
Kaplan Medical Center
Tel-Aviv Sourasky Medical Center
Specjalistyczna Przychodnia Lekarska Medikard
Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
Oddzial Neurologii -- Klinika Neurologii ICZMP
NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
WSS im.Kardynala S. Wyszynskiego
Instytut Psychiatrii i Neurologii II Oddzial Neurologii
Kazan State Medical University
City Hospital # 1
City Hospital # 33
District Antiepileptic Centre City Clinical Hospital # 71
Russian Military Medical Academy
Pavlov State Medical University Clinic and Department of Neurology
Sunninghill & Kopano Clinical Trials
Wilgers MR & Medical Centre
Panorama Medi-Clinic
Groote Schuur Hospital
Carl Bremer Hospital
Farmovs Parexel
Inkosi Albert Luthuli Central Hospital
Johannesburg Hospital
Triple M Research
Hospital Sta. Creu i S. Pau
Hospital de Cruces Neurology Department
Hosp. Virgen de las Nieves
Hospital Ruber Internacional de Madrid
Fundacion Jimenez Diaz
Hosp. de Donostia Neurology Department
Hospital Universitario Lozano Blesa Neurology Service
Psychosomatic Center of Dnepropetr. Regional Clinic
Kharkov State Medical University
Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
Epilepsy Center of Municipal Clinical Psychoneurological Hospital
Odessa Regional Clinical Hospital Center for Neurology and Neurosurgery
The James Cook University Hospital
Fylde Coast Hospital
Western Infirmary (Epilepsy)
Royal London Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Retigabine (INN), Ezogabine (USAN)

Arm Description

Retigabine (Ezogabine): all subjects

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)

An AE is defined as 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. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations and is associated with impaired liver function. TEAEs refer to an AE for which the onset was on or after Retigabine dose in this study and on or before 30 days after the last Retigabine dose date. AEs that started in the parent study that worsened in this study were also considered as TEAEs. Analysis was performed on the safety population which included participants who took at least 1 dose of study medication after being enrolled in this OLE study.

Number of Participants With TEAEs Leading to Treatment Discontinuation (Disc.)

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A summary of participants with treatment emergent AEs leading to treatment disc. up to 122 months have been presented.

Kaplan-Meier Estimate of the Probability of Disc. From Study Drug

Kaplan-Meier estimate of the probability of disc. at the specified time for all participants is presented. The time frame of premature study disc. was defined as the time from the day of first the study medication to the time of withdrawal from study drug. For those who had a taper dose start date, the time of withdrawal was the day before the start of taper dose. Participants who switched to commercial product were censored at the last dose of study drug (excluding taper). All participants who withdrew from the study/treatment prematurely but did not switch to commercial product were counted as an event. Number of participants continuing on retigabine at each time of withdrawal were analyzed (represented by n=x in the category titles).

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Measurements in the Supine and Standing Position

Vital sign measurements (supine and standing blood pressure ) were obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Evaluations of blood pressure were performed supine at each study visit, and again after the participant had been standing for approximately 2 minutes. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Heart Rate (HR) Measurements in the Supine and Standing Position

Vital sign measurement HR was obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Evaluations of HR was performed supine at each study visit, and again after the participant had been standing for approximately 2 minutes. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Body Temperature

Vital sign measurement temperature was obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Body Weight

Weight in pounds or kilograms was measured in ordinary indoor clothing (without shoes) and was recorded at all study visits during the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Electocardiogram (ECG) Parameters PR, QRS, QT, Corrected QT Interval (QTc) Bazett and QTc Friedericia

A 12-lead ECG was performed at all study visits during the Open-Label Treatment Phase during the first year of the open-label extension study (Months 1, 3, 6, 9, 12) and at the end of each 12 month study cycle that the participant was enrolled (i.e., second year, third year, fourth year, etc.). The ECG parameters that were assessed were PR interval, QRS interval, QRS duration, QT interval, and QTc interval. QT intervals were corrected using both Bazett's and Friedericia's formulas. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Alkaline Phosphatase (Alk. Phos.), Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST)

Clinical chemistry parameters included Alk. Phos., ALT and AST. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium and Urea

Clinical chemistry parameters included bicarbonate, calcium, chloride, cholesterol, Non-fasting Glucose, phosphorus, potassium, sodium and urea. Approximately 7-milliliter sample of blood was drawn for clinical chemistry assays. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Creatinine, Total Bilirubin and Uric Acid

Clinical chemistry parameters included creatinine, total bilirubin and uric acid. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Total Protein

Clinical chemistry parameter included total protein. The clinical laboratory evaluation were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, White Blood Cells (WBC)

Hematology parameters included eosinophils, basophils lymphocytes, monocytes, neutrophils, platelet count , and WBC. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Hematocrit

Blood samples for the assessment of clinical laboratory parameter hematocrit were collected at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Hemoglobin

The hematology parameters included hemoglobin. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Hematology Parameter Red Blood Cells (RBC)

The hematology parameters included RBC. The clinical laboratory evaluation were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data 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 is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. Urinalysis assessments were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Urine Potential of Hydrogen (pH)

Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. Urinalysis assessments were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Volume

The post-void residual urine volume in the bladder was evaluated by transabdominal ultrasound. The urine bladder was sonicated from two directions perpendicular to one another, and the volume calculated automatically. A PVR bladder ultrasound to assess urinary retention was performed during the first year at Months 1, 3 and 12 and at the end of each 12 month study cycle that the participant was enrolled (i.e., second year, third year, fourth year, etc.) in the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Change From Baseline in the Urinary Voiding Function [UVF] (Assessed Using the American Urological Association [AUA] Symptom Index)

AUA Symptom Index was completed during the first year at Months 1, 3, 12 and at the end of each 12 month study cycle that the participant was enrolled in the Open-Label Treatment Phase (second, third, fourth year) to assess the participant UVF. The questions were scored on a scale of 0 to 5, with 0 (not at all) to 5 (almost always). A Symptom Index is determined by adding the scores. The lowest possible score is 0 and the highest possible score is 35, which would represent the highest level of pain and discomfort. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed represented by (n=x).

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

The QOLIE-31-P questionnaire contained 30 items. The subscale scores (seizure worry, overall QOL, emotional well-being, energy-fatigue, cognitive, medication effects, social functioning), the final QOLIE-31-P score and the weighted total score (overall assessment) were calculated according to the scoring algorithm defined by the author. Scores range from 0 to 100 with higher scores indicating better function. Baseline was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. NA indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Percentage of Participants With Abnormal Results of Physical Examination

A complete physical examination was performed at the end of each 12 month study cycle (i.e., first year, second year, third year, etc.) during the Open-Label Treatment Phase. The investigator assessed the skin at every clinic visit. If abnormal skin discoloration was confirmed, the participant continued to be followed by the dermatologist. If the abnormal skin discoloration was not confirmed, the investigator resumed assessing the participants skin at all scheduled clinic visits. Only data for abnormal values on physical examination have been presented. Only those participants available at the specified time points were analyzed.

Percentage of Participants With Abnormal Results of Neurological Examination

A complete neurological examination was performed at the end of each 12 month study cycle (i.e., first year, second year, third year, etc.) during the Open-Label Treatment Phase. Abnormal results were categorized as Abnormal-Not Clinically Significant (A-NCS) and Abnormal and Clinically Significant (A-CS). Only data for abnormal values on neurological examination have been presented. Only those participants available at the specified time points were analyzed.

Secondary Outcome Measures

Percentage of Participants With Retinal Pigmentary Abnormalities (RPA)

RPA was determined by either an ophthalmologist or retina specialist. RPA is the composite endpoint assessed by its components: pigmentary abnormalities (PA) in the macula, PA in the peripheral retina (PR), PA in both macula and PR and PA at location unspecified. Only those participants with >=1 ophthalmology exam on or before last dose of retigabine are presented..

Percentage of Participants With Pigmentation of Non-retinal Ocular Tissue (Non-ret. Pig. Abn)

Non-retinal ocular tissue abnormalities were determined by either an ophthalmologist or retina specialist. Non-ret. Pig. Abn is a composite endpoint assessed by its components: abnormal pigmentation (ABP) of the sclera and/or conjunctiva, ABP of the cornea, ABP of the iris and ABP of the lens. Only those participants with >=1 ophthalmology exam on or before last dose of retigabine are presented.

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

Abnormal discoloration of the skin was determined by a dermatologist. The parameters assessed were abnormal discoloration of the skin, abnormal discoloration of the lips, abnormal discoloration of the nails, abnormal discoloration of the mucosa, abnormal discoloration of sun-exposed tissue, abnormal discoloration of non sun-exposed tissue. Only those participants with at least one skin exam by the investigator or dermatologist on or before the last dose of retigabine or dermatologist-confirmed discoloration with start date on or before the date of last dose of retigabine are presented.

Percentage of Participants With a Clinically Significant Decrease (CSD) in Visual Acuity (VA) From Initial Examination

VA refers to the clarity of vision. The parameters assessed were CSD in VA from initial examination which can be explained and CSD in VA from initial examination which cannot be explained. Only those participants with both initial and at least 1 follow-up exam while on retigabine are presented.

Percentage of Participants With Decrease in Confrontation Visual Field From Initial Examination

The parameter assessed was decrease in confrontation visual field from initial examination. Only those participants with data available at the indicated time point were analyzed. Only those participants with both initial and at least 1 follow-up exam while on retigabine are presented.

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. Only those participants available at the specified time points were analyzed.

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.

Percentage Change in the 28-day Partial Seizure Rate From the Baseline Phase (Obtained During the 8-week Baseline Period of Study VRX-RET-E22-302) to Open-label Treatment.

28-day partial seizure rate observed during the OLE period was compared to the 28-day partial seizure rate observed during the Baseline phase of the double-blind parent study VRX-R ET-E22-302. Percent change from Baseline in 28-day total partial seizure rate was calculated as ([28-day partial seizure frequency for the period of interest - Baseline 28-day partial seizure frequency] / Baseline 28-day partial seizure frequency) × 100 percent. A negative percent change indicated a reduction (improvement) from Baseline, so the best possible outcome was -100 percent. Only those participants with data available at the indicated time point were analyzed.

Percentage of Participants With 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

A Responder was defined as a participant with >=50 percent decrease from Baseline in the 28-day partial seizure frequency, i.e., a percent change from Baseline less than or equal to -50 percent. The percentage of responders from Baseline phase of the parent study (VRX-RET-E22-302) to open label treatment have been presented.

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

Seizure free for any continuous 6 months is defined as no seizures occuring during any consecutive 180 days between the first date (Baseline) and the last date (before tapering of dose). The number of participants who were seizure free for 6 continuous months within the 121 month OLE period have been presented.

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

Seizure free for any continuous 12 months is defined as no seizures occurring during any consecutive 360 days. Number of participants who were seizure free for 12 continuous months within the 121 month OLE period have been presented.

Percentage of Seizure Free Days

A seizure free day 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. Percentage of seizure free days is calculated as Number of seizure free days / number of applicable days × 100 percent. Only those participants with data available at the indicated time point were analyzed.

Full Information

NCT ID

NCT00310388

First Posted

March 30, 2006

Last Updated

October 16, 2018

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00310388

Brief Title

Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097

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-E22-302)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Terminated

Why Stopped

No longer any benefit in collecting data since retigabine has been withdrawn from market.

Study Start Date

July 5, 2006 (Actual)

Primary Completion Date

April 18, 2017 (Actual)

Study Completion Date

May 24, 2018 (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

This Phase 3 trial is an open-label extension study of the placebo-controlled, double-blind VRX-RET-E22-302 trial. Patients who have completed the VRX-RET-E22-302 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 the subject withdraws from the study or until the program is discontinued. Patients will be recruited from 55-60 sites in Europe, Israel, Australia, and South Africa. The primary objective of the 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 double-blind Study VRX-RET-E22-302. Secondary objectives are: to evaluate efficacy of long-term treatment with retigabine and patient quality of life and to evaluate whether retinal pigmentation, unexplained vision loss, pigmentation of non-retinal ocular tissue, and discoloration of nails, lips, skin or mucosa change over time after discontinuation of retigabine.

Detailed Description

This Phase 3 trial is an open-label extension study of the placebo-controlled, double-blind VRX-RET-E22-302 trial. Patients who have completed the VRX-RET-E22-302 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 55-60 sites in Europe, Israel, Australia, and South Africa. 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

Partial Seizures, Epilepsy, RTG115097, Complex Partial Seizures, Anticonvulsant, Potassium Channels, Epilepsies, Partial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

376 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Retigabine (INN), Ezogabine (USAN)

Arm Type

Experimental

Arm Description

Retigabine (Ezogabine): all subjects

Intervention Type

Drug

Intervention Name(s)

Retigabine (INN), Ezogabine (USAN)

Other Intervention Name(s)

GW582892X, D-23129, GKE-841

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 patients receives between 600 and 1200 mg of retigabine per day. The duration will be until the completion of the trial, or until the patient withdraws from the trial.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)

Description

Time Frame

Up to 122 months

Title

Number of Participants With TEAEs Leading to Treatment Discontinuation (Disc.)

Description

Time Frame

Up to 122 months

Title

Kaplan-Meier Estimate of the Probability of Disc. From Study Drug

Description

Time Frame

Up to 122 months

Title

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Measurements in the Supine and Standing Position

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Heart Rate (HR) Measurements in the Supine and Standing Position

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Body Temperature

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Body Weight

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Electocardiogram (ECG) Parameters PR, QRS, QT, Corrected QT Interval (QTc) Bazett and QTc Friedericia

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Alkaline Phosphatase (Alk. Phos.), Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST)

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium and Urea

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Creatinine, Total Bilirubin and Uric Acid

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Total Protein

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, White Blood Cells (WBC)

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Hematocrit

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Hemoglobin

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Hematology Parameter Red Blood Cells (RBC)

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Urine Specific Gravity

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Urine Potential of Hydrogen (pH)

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Volume

Description

Time Frame

Baseline and up to 122 months

Title

Change From Baseline in the Urinary Voiding Function [UVF] (Assessed Using the American Urological Association [AUA] Symptom Index)

Description

Time Frame

Baseline and up to 122 months

Title

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

Description

Time Frame

Baseline and up to 122 months

Title

Percentage of Participants With Abnormal Results of Physical Examination

Description

Time Frame

Baseline and up to 122 months

Title

Percentage of Participants With Abnormal Results of Neurological Examination

Description

Time Frame

Baseline and up to 122 months

Secondary Outcome Measure Information:

Title

Percentage of Participants With Retinal Pigmentary Abnormalities (RPA)

Description

Time Frame

Up to 121 months

Title

Percentage of Participants With Pigmentation of Non-retinal Ocular Tissue (Non-ret. Pig. Abn)

Description

Time Frame

Up to 121 months

Title

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

Description

Time Frame

Up to 121 months

Title

Percentage of Participants With a Clinically Significant Decrease (CSD) in Visual Acuity (VA) From Initial Examination

Description

Time Frame

Up to 121 months

Title

Percentage of Participants With Decrease in Confrontation Visual Field From Initial Examination

Description

Time Frame

Up to 121 months

Title

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

Description

Time Frame

3 years and 10 months

Title

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

Description

Time Frame

3 years and 10 months

Title

Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

Description

Time Frame

3 years and 10 months

Title

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

Description

Time Frame

3 years and 10 months

Title

Percentage Change in the 28-day Partial Seizure Rate From the Baseline Phase (Obtained During the 8-week Baseline Period of Study VRX-RET-E22-302) to Open-label Treatment.

Description

Time Frame

Baseline and up to 121 months

Title

Percentage of Participants With 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

Description

Time Frame

Baseline and up to 121 months

Title

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

Description

Time Frame

Up to 6 continuous months within the 121 months period

Title

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

Description

Time Frame

Up to 12 continuous months within the 121 months period

Title

Percentage of Seizure Free Days

Description

Time Frame

Up to 121 months

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

Institute of Clniical Neurosciences

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

North Coast Neurology Centre

City

Maroochydore

State/Province

Queensland

ZIP/Postal Code

4558

Country

Australia

Facility Name

Flinders Medical Centre

City

Bedford Park

State/Province

South Australia

ZIP/Postal Code

5041

Country

Australia

Facility Name

Royal Melbourne Hospital

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3050

Country

Australia

Facility Name

Austin & Repatriation Medical Centre

City

West Heidelberg

State/Province

Victoria

ZIP/Postal Code

3081

Country

Australia

Facility Name

General Hospital Middelheim -- Department of Neurology

City

Antwerp

ZIP/Postal Code

B-2020

Country

Belgium

Facility Name

AZ Sint-Jan

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Centre Neurologique William Lennox

City

Ottignies

ZIP/Postal Code

1340

Country

Belgium

Facility Name

Hopital Civil de Steasbourg Clinique Neurologie

City

Levallois-Perret

ZIP/Postal Code

92594

Country

France

Facility Name

Hopital Neurologique Pierre Wertheimer

City

Lyon

ZIP/Postal Code

69003

Country

France

Facility Name

CHU Pontchaillou

City

Rennes Cedex

ZIP/Postal Code

35033

Country

France

Facility Name

Centre Medical de La Teppe

City

Tain L'Hermitage, 26

ZIP/Postal Code

26600

Country

France

Facility Name

Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen

City

Erlangen

State/Province

ZIP/Postal Code

91054

Country

Germany

Facility Name

Universitaet Giessen / Marburg Neurologie

City

Marburg

State/Province

ZIP/Postal Code

35033

Country

Germany

Facility Name

Universitaetsklinik Mainz Neurologische Klinik

City

Mainz

State/Province

ZIP/Postal Code

55101

Country

Germany

Facility Name

University of Bonn -- Department for Epileptplogy

City

Bonn

ZIP/Postal Code

D-53105

Country

Germany

Facility Name

Private Neurologische Paraxis

City

Muenchen, BY

ZIP/Postal Code

80333

Country

Germany

Facility Name

Universitaetslinkum Ulm Poliklinik fuer Neurologie

City

Ulm, BW

ZIP/Postal Code

89081

Country

Germany

Facility Name

Pecs University of Science, Clinic of Neurology

City

Pecs

State/Province

Ret

ZIP/Postal Code

Country

Hungary

Facility Name

Orszagos Pszichiatriai es Neurologiai Intezet

City

Budapest

ZIP/Postal Code

1021

Country

Hungary

Facility Name

Orszagos Idegsebeszeti Tudomanyos Intezet

City

Budapest

ZIP/Postal Code

1145

Country

Hungary

Facility Name

Assaf Harofeh Medical Center

City

Beer Yaakov

ZIP/Postal Code

70300

Country

Israel

Facility Name

Rambam Medical Center

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Wolfson Medical Center

City

Holon

ZIP/Postal Code

58100

Country

Israel

Facility Name

Western Galilee Hospital

City

Nahariya

ZIP/Postal Code

22100

Country

Israel

Facility Name

Chaim Sheba Medical Center

City

Ramat Gan

ZIP/Postal Code

52621

Country

Israel

Facility Name

Kaplan Medical Center

City

Rechovot

ZIP/Postal Code

76100

Country

Israel

Facility Name

Tel-Aviv Sourasky Medical Center

City

Tel Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Specjalistyczna Przychodnia Lekarska Medikard

City

Padlewskiego 4

State/Province

Plock

ZIP/Postal Code

09-402

Country

Poland

Facility Name

Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"

City

Plac Hallera 5

State/Province

Warszawa

ZIP/Postal Code

03-464

Country

Poland

Facility Name

Oddzial Neurologii -- Klinika Neurologii ICZMP

City

U1. Parzeczewska 35

State/Province

Zgierz

ZIP/Postal Code

95-100

Country

Poland

Facility Name

NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"

City

Bialystok

Country

Poland

Facility Name

Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika

City

Gdansk

ZIP/Postal Code

80-803

Country

Poland

Facility Name

WSS im.Kardynala S. Wyszynskiego

City

Lublin

ZIP/Postal Code

20-718

Country

Poland

Facility Name

Instytut Psychiatrii i Neurologii II Oddzial Neurologii

City

Warszawa

ZIP/Postal Code

02-957

Country

Poland

Facility Name

Kazan State Medical University

City

Kazan

ZIP/Postal Code

420012

Country

Russian Federation

Facility Name

City Hospital # 1

City

Moscow

ZIP/Postal Code

117049

Country

Russian Federation

Facility Name

City Hospital # 33

City

Moscow

Country

Russian Federation

Facility Name

District Antiepileptic Centre City Clinical Hospital # 71

City

Moscow

Country

Russian Federation

Facility Name

Russian Military Medical Academy

City

St. Petersburg

ZIP/Postal Code

194044

Country

Russian Federation

Facility Name

Pavlov State Medical University Clinic and Department of Neurology

City

St. Petersburg

Country

Russian Federation

Facility Name

Sunninghill & Kopano Clinical Trials

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2157

Country

South Africa

Facility Name

Wilgers MR & Medical Centre

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0001

Country

South Africa

Facility Name

Panorama Medi-Clinic

City

Parow

State/Province

W Cape

ZIP/Postal Code

7550

Country

South Africa

Facility Name

Groote Schuur Hospital

City

Cape Town

State/Province

ZIP/Postal Code

7925

Country

South Africa

Facility Name

Carl Bremer Hospital

City

Belville, W Cape

ZIP/Postal Code

7531

Country

South Africa

Facility Name

Farmovs Parexel

City

BleomFontein, Free State

ZIP/Postal Code

9300

Country

South Africa

Facility Name

Inkosi Albert Luthuli Central Hospital

City

Durban, KZ-Natal

ZIP/Postal Code

4091

Country

South Africa

Facility Name

Johannesburg Hospital

City

Johannesburg, Gauteng

ZIP/Postal Code

2193

Country

South Africa

Facility Name

Triple M Research

City

Port Elisabeth, E Cape

ZIP/Postal Code

6001

Country

South Africa

Facility Name

Hospital Sta. Creu i S. Pau

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Facility Name

Hospital de Cruces Neurology Department

City

Bilbao

ZIP/Postal Code

48903

Country

Spain

Facility Name

Hosp. Virgen de las Nieves

City

Granada

ZIP/Postal Code

18014

Country

Spain

Facility Name

Hospital Ruber Internacional de Madrid

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Fundacion Jimenez Diaz

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Hosp. de Donostia Neurology Department

City

San Sebastian

ZIP/Postal Code

20014

Country

Spain

Facility Name

Hospital Universitario Lozano Blesa Neurology Service

City

Zaragoza

ZIP/Postal Code

50009

Country

Spain

Facility Name

Psychosomatic Center of Dnepropetr. Regional Clinic

City

Dnepropetrovsk

ZIP/Postal Code

49616

Country

Ukraine

Facility Name

Kharkov State Medical University

City

Kharkov

ZIP/Postal Code

31002

Country

Ukraine

Facility Name

Institute of Neurology, Psychiatry and Narcology of AMS, Ukr

City

Kharkov

ZIP/Postal Code

31068

Country

Ukraine

Facility Name

Epilepsy Center of Municipal Clinical Psychoneurological Hospital

City

Kiev

ZIP/Postal Code

04080

Country

Ukraine

Facility Name

Odessa Regional Clinical Hospital Center for Neurology and Neurosurgery

City

Odessa

ZIP/Postal Code

65025

Country

Ukraine

Facility Name

The James Cook University Hospital

City

Middlesbrough

State/Province

Mersyd

ZIP/Postal Code

TS4 3BY

Country

United Kingdom

Facility Name

Fylde Coast Hospital

City

Blackpool

ZIP/Postal Code

FY3 8BP

Country

United Kingdom

Facility Name

Western Infirmary (Epilepsy)

City

Glasgow

ZIP/Postal Code

G11 6NT

Country

United Kingdom

Facility Name

Royal London Hospital

City

London

ZIP/Postal Code

GT LON E1 1BB

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

VRX-RET-E22-304

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097

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