Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097
- Registration Number
- NCT00310388
- Lead Sponsor
- GlaxoSmithKline
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 376
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Retigabine (INN), Ezogabine (USAN) Retigabine (INN), Ezogabine (USAN) Retigabine (Ezogabine): all subjects
- Primary Outcome Measures
Name Time Method Number of Participants With TEAEs Leading to Treatment Discontinuation (Disc.) Up to 122 months 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) Up to 122 months 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.
Change From Baseline in Body Weight Baseline and up to 122 months 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 Bicarbonate, Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium and Urea Baseline and up to 122 months 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).
Kaplan-Meier Estimate of the Probability of Disc. From Study Drug Up to 122 months 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 Baseline and up to 122 months 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 Body Temperature Baseline and up to 122 months 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 Alkaline Phosphatase (Alk. Phos.), Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) Baseline and up to 122 months 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 Heart Rate (HR) Measurements in the Supine and Standing Position Baseline and up to 122 months 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 Electocardiogram (ECG) Parameters PR, QRS, QT, Corrected QT Interval (QTc) Bazett and QTc Friedericia Baseline and up to 122 months 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 Creatinine, Total Bilirubin and Uric Acid Baseline and up to 122 months 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 Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, White Blood Cells (WBC) Baseline and up to 122 months 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 Hematology Parameter Red Blood Cells (RBC) Baseline and up to 122 months 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 Potential of Hydrogen (pH) Baseline and up to 122 months 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).
Percentage of Participants With Abnormal Results of Neurological Examination Baseline and up to 122 months 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.
Change From Baseline in Total Protein Baseline and up to 122 months 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 Hematocrit Baseline and up to 122 months 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 Baseline and up to 122 months 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 Urine Specific Gravity Baseline and up to 122 months 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 Post-Void Residual (PVR) Bladder Ultrasound Volume Baseline and up to 122 months 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) Baseline and up to 122 months 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 Baseline and up to 122 months 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 Baseline and up to 122 months 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine 3 years and 10 months 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.
Percentage of Participants With Decrease in Confrontation Visual Field From Initial Examination Up to 121 months 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.
Percentage of Participants With 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment Baseline and up to 121 months 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.
Percentage of Participants With Pigmentation of Non-retinal Ocular Tissue (Non-ret. Pig. Abn) Up to 121 months 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.
Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation 3 years and 10 months 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.
Percentage of Participants With Retinal Pigmentary Abnormalities (RPA) Up to 121 months 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 a Clinically Significant Decrease (CSD) in Visual Acuity (VA) From Initial Examination Up to 121 months 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.
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine 3 years and 10 months 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.
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. Baseline and up to 121 months 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.
Number of Participants Who Were Seizure Free for Any 6 Continuous Months Up to 6 continuous months within the 121 months period 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.
Percentage of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa Up to 121 months 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.
Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration 3 years and 10 months 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.
Number of Participants Who Were Seizure Free for Any 12 Continuous Months Up to 12 continuous months within the 121 months period 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 Up to 121 months 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.
Trial Locations
- Locations (67)
Institute of Clniical Neurosciences
🇦🇺Camperdown, New South Wales, Australia
North Coast Neurology Centre
🇦🇺Maroochydore, Queensland, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Hopital Civil de Steasbourg Clinique Neurologie
🇫🇷Levallois-Perret, France
CHU Pontchaillou
🇫🇷Rennes Cedex, France
Centre Medical de La Teppe
🇫🇷Tain L'Hermitage, 26, France
Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
🇩🇪Erlangen, BY, Germany
Private Neurologische Paraxis
🇩🇪Muenchen, BY, Germany
Universitaetsklinik Mainz Neurologische Klinik
🇩🇪Mainz, RP, Germany
Rambam Medical Center
🇮🇱Haifa, Israel
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
🇵🇱Plac Hallera 5, Warszawa, Poland
Instytut Psychiatrii i Neurologii II Oddzial Neurologii
🇵🇱Warszawa, Poland
Sunninghill & Kopano Clinical Trials
🇿🇦Johannesburg, Gauteng, South Africa
Panorama Medi-Clinic
🇿🇦Parow, W Cape, South Africa
Groote Schuur Hospital
🇿🇦Cape Town, WC, South Africa
Wilgers MR & Medical Centre
🇿🇦Pretoria, Gauteng, South Africa
Carl Bremer Hospital
🇿🇦Belville, W Cape, South Africa
Farmovs Parexel
🇿🇦BleomFontein, Free State, South Africa
Inkosi Albert Luthuli Central Hospital
🇿🇦Durban, KZ-Natal, South Africa
Johannesburg Hospital
🇿🇦Johannesburg, Gauteng, South Africa
Hospital Sta. Creu i S. Pau
🇪🇸Barcelona, Spain
Triple M Research
🇿🇦Port Elisabeth, E Cape, South Africa
Hospital de Cruces Neurology Department
🇪🇸Bilbao, Spain
Hosp. Virgen de las Nieves
🇪🇸Granada, Spain
Hospital Ruber Internacional de Madrid
🇪🇸Madrid, Spain
Hosp. de Donostia Neurology Department
🇪🇸San Sebastian, Spain
Hospital Universitario Lozano Blesa Neurology Service
🇪🇸Zaragoza, Spain
Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
🇺🇦Kharkov, Ukraine
Psychosomatic Center of Dnepropetr. Regional Clinic
🇺🇦Dnepropetrovsk, Ukraine
The James Cook University Hospital
🇬🇧Middlesbrough, Mersyd, United Kingdom
Western Infirmary (Epilepsy)
🇬🇧Glasgow, United Kingdom
Fylde Coast Hospital
🇬🇧Blackpool, United Kingdom
Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
🇧🇪Leuven, Belgium
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Oddzial Neurologii -- Klinika Neurologii ICZMP
🇵🇱U1. Parzeczewska 35, Zgierz, Poland
Western Galilee Hospital
🇮🇱Nahariya, Israel
Orszagos Pszichiatriai es Neurologiai Intezet
🇭🇺Budapest, Hungary
Orszagos Idegsebeszeti Tudomanyos Intezet
🇭🇺Budapest, Hungary
Centre Neurologique William Lennox
🇧🇪Ottignies, Belgium
NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
🇵🇱Bialystok, Poland
WSS im.Kardynala S. Wyszynskiego
🇵🇱Lublin, Poland
Russian Military Medical Academy
🇷🇺St. Petersburg, Russian Federation
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Pecs University of Science, Clinic of Neurology
🇭🇺Pecs, Ret, Hungary
General Hospital Middelheim -- Department of Neurology
🇧🇪Antwerp, Belgium
AZ Sint-Jan
🇧🇪Brugge, Belgium
Assaf Harofeh Medical Center
🇮🇱Beer Yaakov, Israel
Wolfson Medical Center
🇮🇱Holon, Israel
Kaplan Medical Center
🇮🇱Rechovot, Israel
Specjalistyczna Przychodnia Lekarska Medikard
🇵🇱Padlewskiego 4, Plock, Poland
Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
🇵🇱Gdansk, Poland
Pavlov State Medical University Clinic and Department of Neurology
🇷🇺St. Petersburg, Russian Federation
City Hospital # 1
🇷🇺Moscow, Russian Federation
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Kharkov State Medical University
🇺🇦Kharkov, Ukraine
City Hospital # 33
🇷🇺Moscow, Russian Federation
Odessa Regional Clinical Hospital Center for Neurology and Neurosurgery
🇺🇦Odessa, Ukraine
District Antiepileptic Centre City Clinical Hospital # 71
🇷🇺Moscow, Russian Federation
Epilepsy Center of Municipal Clinical Psychoneurological Hospital
🇺🇦Kiev, Ukraine
Austin & Repatriation Medical Centre
🇦🇺West Heidelberg, Victoria, Australia
Universitaet Giessen / Marburg Neurologie
🇩🇪Marburg, HE, Germany
Universitaetslinkum Ulm Poliklinik fuer Neurologie
🇩🇪Ulm, BW, Germany
Hopital Neurologique Pierre Wertheimer
🇫🇷Lyon, France
Royal London Hospital
🇬🇧London, United Kingdom
University of Bonn -- Department for Epileptplogy
🇩🇪Bonn, Germany
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain