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)

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

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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)

时间窗: 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)

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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)

时间窗: 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

时间窗: 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

时间窗: 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.