Open-label Extension Study of the Phase 3 VRX-RET-E22-301 Double-Blind Trial
- Conditions
- Epilepsy
- Registration Number
- NCT00310375
- Lead Sponsor
- GlaxoSmithKline
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 181
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Change From Baseline in Body Temperature Baseline and Up to Month 108 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 Hematology Parameters- Bands, Basophils, Eosinophils, Lymphocytes, Metamyelocyte, Monocytes, Neutrophils, Platelets, White Blood Cells Count (WBC) Baseline and Up to Month 108 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.
Number of Participants With Treatment-emergent Adverse Events Leading to Withdrawal From Study Drug Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Heart Rate Baseline and Up to Month 108 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 Haematocrit Baseline and Up to Month 108 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).
Number of Participants With Treatment-emergent Serious Adverse Event (SAE) and Adverse Event (AE) Assessed up to a maximum of 9 years 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.
Change From Baseline in Blood Pressure Baseline and Up to Month 108 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 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) Baseline and Up to Month 108 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 Electrocardiogram (ECG) Parameter-QRS Axis Baseline and Up to Month 108 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 Chemistry Parameters -Creatinine, Total Bilirubin (TB), Uric Acid (UA) Baseline and Up to Month 108 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 Weight Baseline and Up to Month 108 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) Parameter-RR Interval Baseline and Up to Month 108 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 Haemoglobin Baseline and Up to Month 108 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 Parameter-Total Protein Baseline and Up to Month 108 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 Chemistry Parameters-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) Baseline and Up to Month 108 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 Urine Specific Gravity Baseline and Up to Month 108 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.
Number of Participants With Abnormal Results of Neurological Examination Up to Month 108 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 Assessed up to a maximum of 9 years 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.
Change From Baseline in Hematology Parameter-Red Blood Cell Count Baseline and Up to Month 108 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 Chemistry Parameters-Bicarbonate, Blood Urea Nitrogen (BUN), Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium, Urea Baseline and Up to Month 108 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 Urine Power of Hydrogen (pH) Baseline and Up to Month 108 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 Baseline and Up to Month 108 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 Baseline and Up to Month 108 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 Up to Month 108 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 Pigmentation of Retinal Ocular Tissue Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 2 years and 9 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 and non-retinal ocular pigmentary abnormality.
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine 2 years 9 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.
Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation 2 years 9 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.
Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration 2 years 9 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.
- Secondary Outcome Measures
Name Time Method Percentage Change From Baseline in the 28-day Partial Seizure Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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 Assessed up to a maximum of 9 years 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)
Trial Locations
- Locations (51)
CIF BIOTEC, Medica Sur
🇲🇽Tlalpan, DF, Mexico
Antiguo Hospital Civil de Guadalajara
🇲🇽Guadalajara, Jalisco, Mexico
Neurology Clinic
🇺🇸Northport, Alabama, United States
Clinical Trials Inc.
🇺🇸Little Rock, Arkansas, United States
UCSD Thornton Hospital
🇺🇸La Jolla, California, United States
North Alabama Neuroscience Research Associates
🇺🇸Huntsville, Alabama, United States
University of Southern California -- Keck School of Medicine
🇺🇸Los Angeles, California, United States
West Los Angeles VA Healthcare Center
🇺🇸Los Angeles, California, United States
Minnesota Epilepsy Group, P.A.
🇺🇸Saint Paul, Minnesota, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Neurological Clinic of Texas
🇺🇸Dallas, Texas, United States
University of Virginia Comprehensive Epilepsy Program
🇺🇸Charlottesville, Virginia, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Foothills Medical Center
🇨🇦Calgary, Alberta, Canada
Hospital Universitario Prof Edgard Santos -- UFBA
🇧🇷Salvador, BA, Brazil
Instituto Nacional de Neurologia y Neurocirugia
🇲🇽La Fama, DF, Mexico
Centro Medico
🇲🇽Mexico, DF, Mexico
Health Sciences Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Fundacion Lennox
🇦🇷Cordoba, CRD, Argentina
Sanatorio del Salvador II
🇦🇷Cordoba, CRD, Argentina
CHUM -- Hôpital Notre-Dame
🇨🇦Montréal, Quebec, Canada
Hospital y Clinica OCA S.A. de C.V.
🇲🇽Monterrey, Nuevo Leon, Mexico
Hospital Central Dr. Ignacio Morones Prieto
🇲🇽San Luis Potosi, SLP, Mexico
University of Alabama -- Department of Neurology/Epilepsy Center
🇺🇸Birmingham, Alabama, United States
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Miami
🇺🇸Miami, Florida, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Memorial Hermann Hospital
🇺🇸Houston, Texas, United States
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, CRD, Argentina
Delta Waves
🇺🇸Colorado Springs, Colorado, United States
University of Florida -- Shands Jacksonville
🇺🇸Jacksonville, Florida, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Asheville Neurology Specialists
🇺🇸Asheville, North Carolina, United States
The Comprehensive Epilepsy Care Center for Children and Adults
🇺🇸Chesterfield, Missouri, United States
Hospital General de Agudos "Dr. J.M. Ramos Mejia"
🇦🇷Capital Federal, CBA, Argentina
Hospital General de Agudos "Dr. Teodoro Alvarez"
🇦🇷Capital Federal, CBA, Argentina
Hospital Sao Paulo -- Escola Paulista de Medicina -- UNIFESP
🇧🇷Sao Paulo, SP, Brazil
Hospital das Clinicas de Ribeirao Preto -- Universidade de Sa Neurologia
🇧🇷Ribeirao Preto, SP, Brazil
Glenrose Rehabilitation Center
🇨🇦Edmonton, Alberta, Canada
Hospital de Psiquiatria San Fernando, IMSS
🇲🇽Mexico, DF, Mexico
University of Colorado Department Of Neurology
🇺🇸Denver, Colorado, United States
Lovelace Scientific Resources
🇺🇸Sarasota, Florida, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Hospital das Clinicas da Fac de Medicina de Sao Paulo
🇧🇷Sao Paulo, SP, Brazil
Medical University of Ohio at Toledo
🇺🇸Toledo, Ohio, United States
Oregon Neurology PC
🇺🇸Tualatin, Oregon, United States
Hospital Italiano de Buenos Aires
🇦🇷Capital Federal, CBA, Argentina
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States