Clinical Trial Results:
A Multicentre, Open-Label, Long-Term, Safety and Tolerability Study of Retigabine Immediate Release (IR) in Adults with Partial-Onset Seizures (Extension of Study RGB113905)
Summary
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EudraCT number |
2010-022777-34 |
Trial protocol |
DE NL IT ES BG BE PL |
Global end of trial date |
13 Sep 2017
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Results information
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Results version number |
v3(current) |
This version publication date |
21 Jun 2018
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First version publication date |
22 Dec 2017
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Other versions |
v1 , v2 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
113413
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Apr 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Sep 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess long-term safety and tolerability of flexibly dosed retigabine immediate release (IR) as adjunctive therapy in adults with partial-onset seizures (POS) who completed open-label flexible dose Study RGB113905.
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Feb 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
6 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Bulgaria: 5
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Italy: 19
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Russian Federation: 42
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Country: Number of subjects enrolled |
Thailand: 8
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Country: Number of subjects enrolled |
Ukraine: 16
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Worldwide total number of subjects |
98
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EEA total number of subjects |
32
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
94
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants with partial-onset seizures (POS) who successfully completed the 20 weeks of treatment in parent study NCT01336621 were recruited in this open-label extension (OLE) study. The study was conducted in two periods, a primary treatment phase and a safety follow-up continuation phase (SFUCP). | ||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Screening was performed on the same day as the final visit of the parent study NCT01336621. A total of 98 participants completed the parent study and opted to enter into this study. All participants received at least one dose of retigabine immediate release (IR) tablets. | ||||||||||||||||||||||||||
Period 1
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Period 1 title |
Primary Reporting Phase (Upto 5.8 years)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
Arms
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Arm title
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Retigabine IR | ||||||||||||||||||||||||||
Arm description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Retigabine immediate release (IR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Five strengths of retigabine IR including 50 mg, 100 mg, 200 mg, 300 mg and 400 mg tablets were provided. Participants entering RTG113413 from the parent study continued on the same maintenance dose of retigabine IR as per parent study. The dose was increased in steps of 50 mg to 150 mg/day on a weekly basis. The overall daily dose of retigabine IR was maintained between 300 mg/day (minimum) and 1200 mg/day (maximum).
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Period 2
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Period 2 title |
SFUCP (Upto 2.6 years)
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Is this the baseline period? |
No | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
Arms
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Arm title
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Retigabine IR | ||||||||||||||||||||||||||
Arm description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Retigabine immediate release (IR)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Five strengths of retigabine IR including 50 mg, 100 mg, 200 mg, 300 mg and 400 mg tablets were provided. Participants entering RTG113413 from the parent study continued on the same maintenance dose of retigabine IR as per parent study. The dose was increased in steps of 50 mg to 150 mg/day on a weekly basis. The overall daily dose of retigabine IR was maintained between 300 mg/day (minimum) and 1200 mg/day (maximum).
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Baseline characteristics reporting groups
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Reporting group title |
Retigabine IR
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Reporting group description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). | |||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Retigabine IR
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Reporting group description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). | ||
Reporting group title |
Retigabine IR
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Reporting group description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). |
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End point title |
Number of participants with treatment emergent adverse events (TEAEs) and serious AEs (TESAEs) [1] | ||||||||||
End point description |
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. 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, is a congenital anomaly/ birth defect or is associated with liver injury or impaired liver function. TEAE refers to an AE for which the onset was on or after the date of the first 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 increased in severity during this study were also considered treatment-emergent. The analysis was performed on Safety Population, which included participants who took at least one dose of study medication after they had enrolled into this OLE study.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [2] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with AEs and SAEs: All SFUCP subjects [3] | ||||||||||||
End point description |
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. 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, is a congenital anomaly/ birth defect or is associated with liver injury or impaired liver function. The following AEs were collected in the SFUCP: AEs related to the finding(s) of pigmentation/, discoloration of the eye /skin, AEs related to unexplained vision loss, SAEs, Deaths and Pregnancies. SFUCP collected AEs are those for which onset was 31 days or more after the last dose of retigabine. The analysis was performed on the All SFUCP Subjects population which comprised of all subjects who enter the SFUCP.
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End point type |
Primary
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End point timeframe |
Up to 2.6 years
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [4] - All SFUCP subjects |
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No statistical analyses for this end point |
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End point title |
Number of participants withdrawn due to TEAEs [5] | ||||||||
End point description |
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. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolonged existing hospitalization, results in disability, is a congenital anomaly/birth defect or is associated with liver injury or impaired liver function. TEAE refers to an AE for which the onset was on or after the date of the first retigabine dose and on or before 30 days after the last retigabine dose date.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [6] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with retinal pigmentary abnormalities [7] | ||||||||
End point description |
Number of participants with abnormal findings after eye examination were evaluated. Only retinal pigmentary abnormalities detected on-treatment with retigabine were presented. Retinal pigmentary abnormalities included abnormalities in the macula, peripheral retina and unspecified location. Only those participants with >=1 ophthalmology exam on or before last dose of RTG are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [8] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with pigmentation of non-retinal ocular tissue(s) [9] | ||||||||
End point description |
Number of participants with abnormal findings after eye examination were evaluated. Pigmentation of non-retinal ocular tissue (s) detected on-treatment with retigabine were presented. Non-retinal pigmentary abnormalities included abnormalities in the sclera and/ or conjunctiva, cornea, iris and lens. Only those participants with >=1 ophthalmology exam on or before last dose of RTG are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [10] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with abnormal discoloration of skin [11] | ||||||||||||||||
End point description |
Number of participants with Dermatologist-Confirmed abnormal discoloration of skin including skin around the eyes and eyelids, lips, nails, or mucosa were evaluated. Only abnormalities occurring on-treatment with retigabine were presented. Only those participants who had at least one skin exam by the investigator or dermatologist on or before the last dose of RTG or dermatologist-confirmed discoloration with start date on or before the date of last dose of RTG are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [12] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with a clinically significant decrease in visual acuity from initial examination [13] | ||||||||
End point description |
Number of participants with a clinically significant decrease in visual acuity from initial examination were evaluated. Only abnormalities occurring on-treatment with retigabine were presented. Only those participants with both initial and at least 1 follow-up exam while on RTG treatment are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [14] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with decrease in confrontational visual field from initial examination [15] | ||||||||
End point description |
Number of participants with a clinically significant decrease in confrontational visual field from initial examination were evaluated. Only abnormalities occurring on-treatment with retigabine were presented. Only those subjects with both initial and at least 1 follow-up exam while on RTG
treatment are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [16] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with potential clinical concern (PCC) values of change from Baseline in vital signs and weight [17] | ||||||||||||||||||||||
End point description |
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured after at least 5 minutes of rest. Body weight was measured without shoes and wearing light clothing. Baseline assessments in this OLE study were defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. Increase or decrease of >=20 in SBP, increase or decrease of >=15 in DBP and HR were considered as PCC values. Number of participants with PCC values of vital signs for any visit post-Baseline are presented.
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End point type |
Primary
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End point timeframe |
Up to 5.8 years
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Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [18] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in electrocardiogram (ECG) parameter including HR [19] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine to measure HR. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and up to 5.8 years
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Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [20] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in ECG parameter including PR interval, QRS duration, uncorrected QT interval, corrected QT by Bazett's formula (QTcB), corrected QT by Fridericia's formula (QTcF) and RR interval [21] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine to measure parameters including PR interval, QRS duration, uncorrected QT interval, QTcB, QTcF and RR interval. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline and up to 5.8 years
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Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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Notes [22] - Safety Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with clinical chemistry parameters of PCC [23] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of participants with chemistry parameters of PCC at 'any visit post-Baseline' are presented. Chemistry parameters for which PCC values were identified were alanine aminotransferase (ALT) (if value >=3 * upper limit of normal [ULN]), alkaline phosphatase (alk.phosphatase) (if value >=3*ULN), aspartate aminotransferase (AST) (if value >=3*ULN), calcium (if value <=1.8962 or >=2.8692), carbon-di-oxide (CO2) (if value <=18 or >=36), chloride (if value <=92 or >=112), creatine kinase (if value >=3*ULN), direct bilirubin (if value >=1.5*ULN), glucose (if value <=2.7755 or >=11.102), lactate dehydrogenase (LD) (if value >=3*ULN), magnesium (if value <0.36 or >2.50), potassium (if value <=3.0 or >=6.0), sodium (if value <=127 or >=153), total bilirubin (if value >=1.5*ULN), total protein (if value <45 or >100), blood urea nitrogen (BUN) (if value >=14.28). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [24] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Number of participants with hematology parameters of PCC [25] | ||||||||||||||||||||||
End point description |
Blood samples were collected from participants to evaluate hematology parameters. Number of participants with clinical hematology parameters of PCC at 'any visit post-Baseline' are presented. Hematology parameters for which PCC values were identified were eosinophils (if value is >0.8), hematocrit (if value is <=0.32 for males and <=0.28 for females), platelet count (if value is <=100 or >=550), total neutrophils (if value is <=1.8), white blood cells (WBC) (if value is <=2.8 or >=16). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||||||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
Notes [26] - Safety Population |
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of participants with urinalysis parameters of PCC [27] | ||||||||||||||||||||
End point description |
Urine samples were collected from participants at specific time points. Number of participants with urinalysis parameters of PCC at 'any visit post-Baseline' are presented. Urinalysis parameters for which PCC values were identified were albumin/creatinine ratio (if value is >11.3), red blood cells (RBC) (if value is 3-5 or higher), WBC (if value is 5-10 or higher for male and 10-15 or higher for females), specific gravity (if value is <1.001 or >1.035) and potential of hydrogen (pH) (if value is <4.6 or >8.0). Only those participants with data available at specific time points were analyzed (represented by n=X in the category titles).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||||||||||
Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||
|
|||||||||||||||||||||
Notes [28] - Safety Population |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in albumin and total protein [29] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including albumin and total protein. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [30] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in alk. phosphatase, ALT, AST, creatine kinase and LD levels [31] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including alk. phosphatase, ALT, AST, creatine kinase and LD. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [32] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in direct bilirubin, total bilirubin and creatinine [33] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including direct bilirubin, total bilirubin and creatinine. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [34] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in BUN/creatinine ratio [35] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including BUN/creatinine ratio. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [36] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in calcium, chloride, CO2, glucose, potassium, magnesium, sodium and BUN [37] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical chemistry parameters including calcium, chloride, CO2, glucose, potassium, magnesium, sodium and BUN. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Notes [38] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in absolute basophils, absolute eosinophils, absolute lymphocytes, absolute monocytes, absolute total neutrophils, platelet count and WBC count [39] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including absolute basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count and WBC count. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Notes [40] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) levels [41] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including hemoglobin and MCHC. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [42] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in hematocrit levels [43] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including hematocrit. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [44] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in mean corpuscle hemoglobin (MCH) levels [45] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including MCH. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [46] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in mean corpuscle volume (MCV) and mean platelet volume (MPV) levels [47] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including MCV and MPV. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [48] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in RBC count [49] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including RBC count. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [50] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in percent basophils, percent eosinophils, percent lymphocytes, percent monocytes, percent neutrophils and RBC distribution width (RDW) levels [51] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for evaluation of change from Baseline in clinical hematology parameters including percent basophils, eosinophils, lymphocytes, monocytes, neutrophils and RDW. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [52] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in urine albumin creatinine ratio [53] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including albumin creatinine ratio. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [54] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in urine albumin levels [55] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including albumin levels. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [56] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from baseline in urine creatinine levels [57] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Urine samples were collected from participants for evaluation of change from Baseline in urinalysis parameters including creatinine levels. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||||||||||||||||||||||||||||
Notes [57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [58] - Safety Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Changes from Baseline in American Urological Association Symptom Scale (AUA SS) score [59] | ||||||||||||||||||||||
End point description |
The effect of retigabine on bladder function was assessed using AUA symptom index. It is a 7-item Likert-scored scale ranging from 0 (no symptom at all) to 5 (almost always symptoms present) with a total possible score of 35. AUA SS score is the sum of the responses to these seven questions. The total score for all questions was classified as mild (0 to 7), moderate (8 to 19), or severe (>19). Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||
Notes [59] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
Notes [60] - Safety Population |
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||
End point title |
Change from Baseline in Post-Void Residual (PVR) bladder ultrasound urine volume [61] | ||||||||||||||||||||||
End point description |
The PVR bladder ultrasound was used to assess urinary retention. Baseline was defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Change from Baseline was defined as post-Baseline value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||||||||||
Notes [61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
Notes [62] - Safety Population |
|||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of participants with suicidal ideation or behavior assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) score [63] | ||||||||||||
End point description |
Number of participants with suicidal ideation or behavior during treatment were assessed using the C-SSRS score scale. It is a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. Participants are classified with respect to extent of suicidal ideation, extent of suicidal behavior, and with respect to self-injurious behavior.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||
Notes [63] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [64] - Safety Population |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of participants experiencing new seizure types [65] | ||||||||||||||||||
End point description |
Number of participants experiencing new seizure type that is seizure not experienced before were summarized. New seizure types were classified into 5 classes including type A (simple partial seizure), type B (complex partial seizure), type C (Partials, evolving to Secondary Generalized Seizures), type D (Generalized, excluding Myoclonic Seizures), type D2 (Myoclonic Seizures) and type E (Unclassified Seizures).
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||||||||||
Notes [65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [66] - Safety Population |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of participants experiencing worsening of seizures [67] | ||||||||
End point description |
Worsening of seizures was defined as an increase in seizure frequency or the occurrence of a new, more severe seizure type, or status epilepticus occurring in a participant without a history of status epilepticus. An increase in seizure frequency was defined as doubling of the 28-day seizure frequency compared to the 28-day Baseline seizure frequency established in the parent study. Number of participants experiencing worsening of seizure during study period are presented.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to 5.8 years
|
||||||||
Notes [67] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||
|
|||||||||
Notes [68] - Safety Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Duration of retigabine exposure [69] | ||||||||||
End point description |
Duration of exposure was calculated from the first dose through the last dose during study including the Taper Phase and presented using median and full range.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||
Notes [69] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||
|
|||||||||||
Notes [70] - Safety Population |
|||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine [71] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 2.6 years
|
||||||||||||
Notes [71] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [72] - All SFUCP Subjects |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine [73] | ||||||||
End point description |
Participants who enter the SFUCP who had an on-treatment finding(s) of abnormal discoloration of skin, lips, nails or mucosa confirmed by a dermatologist entered the SFUCP and underwent assessments performed by a dermatologist at 6-monthly intervals. The assessment of the participant’s skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to 2.6 years
|
||||||||
Notes [73] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||
|
|||||||||
Notes [74] - All SFUCP Subjects |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation [75] | ||||||||||||
End point description |
Retinal pigmentary abnormality was determined by either an ophthalmologist or retina specialist. Retinal pigmentary abnormality included abnormality of macula, peripheral retina and unspecified location. 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 one location (conjunctiva, sclera, cornea, iris or lens), all should be resolved for non-retinal pigmentary abnormality to be considered resolved.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 2.6 years
|
||||||||||||
Notes [75] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
Notes [76] - All SFUCP Subjects |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration [77] | ||||||||||||||||||
End point description |
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. 99999 indicates data was not available due to low number of participants.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Up to 2.6 years
|
||||||||||||||||||
Notes [77] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
|||||||||||||||||||
|
|||||||||||||||||||
Notes [78] - All SFUCP Subjects |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Number of participants experiencing a 0 to <25, 25 to <50, 50 to <75 and 75 to 100 percent reduction in 28 day POS frequency from Baseline | ||||||||||||||
End point description |
The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||||||
|
|||||||||||||||
Notes [79] - Safety Population |
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Percent change from Baseline in 28-day partial-onset seizure frequency | ||||||||||
End point description |
The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Percent change from Baseline in 28-day partial onset seizure frequency was presented as mean and standard deviation (SD). Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621. Percent change from Baseline was calculated as post-Baseline value minus Baseline value divided by Baseline value into 100.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||||
|
|||||||||||
Notes [80] - Safety Population |
|||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of participants experiencing an increase in 28-day partial-onset seizure frequency from Baseline | ||||||||
End point description |
The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Baseline assessments in this OLE study are defined by and taken directly from the Baseline assessments in the parent study NCT01336621.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and up to 5.8 years
|
||||||||
|
|||||||||
Notes [81] - Safety Population |
|||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of participants who remained seizure-free | ||||||||||
End point description |
The seizure frequency was recorded in daily seizure calendar by participants during the treatment period. Number of participants who were treated retigabine for at least 6 months and who remained seizure free for any 6 continuous months as well as number of participants who were treated with retigabine for at least 12 months and who remained seizure free for any 12 continuous months are presented.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Up to 5.8 years
|
||||||||||
|
|||||||||||
Notes [82] - Safety Population |
|||||||||||
No statistical analyses for this end point |
|
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Adverse events information
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Timeframe for reporting adverse events |
On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the end of study treatment (up to 5.8 years).
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Adverse event reporting additional description |
AEs and SAEs were collected in 'Safety Population' for retigabine IR arm and in 'All SFUCP subjects Population' for Retigabine IR in SFUCP arm. The MedDRA version for the Primary Reporting Phase is 19.1. However the SFUCP phase uses version 20.1.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
Retigabine IR in SFUCP
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Reporting group description |
Participants who withdrew from the Open-Label Treatment Phase and who had retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discoloration of nails, lips, skin or mucosa were followed-up in SFUCP following discontinuation of their retigabine, which was the final reporting phase of the study. During SFUCP, participants underwent six monthly comprehensive eye examinations and/or dermatological assessments. Participants were followed-up until the discoloration /pigmentation either resolves or stabilizes, as defined by no change over two consecutive six monthly assessments over at least 12 months after discontinuation of RTG IR . | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Retigabine IR
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Reporting group description |
Eligible participants continued on the same maintenance dose of retigabine IR and the concurrent anti-epileptic drugs (AEDs) as they were taking at Visit 7 (Week 20) in the parent study NCT01336621. After the first week of the study, the dose of retigabine IR could be increased or decreased by 50-150 milligrams per day (mg/day) on a weekly basis. The overall daily dose of retigabine IR was to be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Oct 2013 |
To update the Sponsor Information page including change in Medical Monitor; to add the requirement to re-evaluate all ongoing participants at each clinic visit with respect to the risk versus the benefit of continuing treatment with Retigabine; revision of study conclusion conditions under which participants will continue to receive retigabine treatment; to re-consent all ongoing participants with revised patient information materials detailing the risk of retinal pigmentation, possible vision loss, pigmentation of non retinal ocular tissue, and discolouration of skin, lips, nails or Mucosa; Addition of 6-monthly comprehensive eye assessments by an ophthalmologist/retina specialist to assess for retinal pigmentation and/or unexplained vision loss; Addition of a skin examination by the investigator at scheduled clinic visits; Addition of referral to a dermatologist for abnormal skin discolouration noted by the investigator or reported by the participant, and repeat 6-monthly assessments by the dermatologist for follow-up of confirmed abnormal skin discolouration; Addition of a Safety Follow-Up / Continuation Phase to provide follow-up of participants who are found to have retinal pigmentation, unexplained vision loss, pigmentation of non-retinal ocular tissue or abnormal discolouration of skin, lips, nails or mucosa and who have stopped taking retigabine; Addition of safety endpoints related to abnormal pigmentation of the eye and/or discolouration of the skin, lips, nails or mucosa; Addition of Pharmacogenetics (PGx) sample collection. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
17 parts. withdrew due to AE, however only 16 had a TEAE leading to withdrawal of RTG. 1 part. with a TEAE of seizure, withdrew due to lack of efficacy. 2 further parts. withdrew due to AE but had no TEAEs which led to withdrawal of RTG. |