Clinical Trial Results:
Open-label, multiple dose study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine as adjunctive treatment in subjects aged from 12 years to less than 18 years with partial onset seizures or Lennox-Gastaut syndrome
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Summary
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EudraCT number |
2012-001132-60 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
29 Apr 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Feb 2016
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First version publication date |
27 Feb 2016
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Other versions |
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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 |
RTG113284
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01494584 | ||
WHO universal trial number (UTN) |
- | ||
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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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000116-PIP01-07 | ||
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 |
31 Jan 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Apr 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To characterize the pharmacokinetic (PK) profile of repeat doses of ezogabine/retigabine IR tablet in subjects aged 12 to less than 18 years old.
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Protection of trial subjects |
This pediatric PK study used minimum-volume venipuncture tubes for the PK collections in an effort to minimize blood volume sampled, and distress due to a child’s visual perspective of tube size. Efforts were also made to obtain capillary blood at the time of venipuncture for validation of a PK assay to mitigate future need for venipuncture.
Subjects had standard safety testing, i.e. clinical laboratory tests, vital signs, and physical examinations; to monitor for the known retigabine/ezogabine pharmacologic effects, baseline and post-dose testing of post-void residual ultrasounds (urinary retention) and electrocardiogram (ECG) (QT prolongation) were required.
The suicidality risk with anti-epileptic drugs was assessed using the Columbia Suicide Severity Rating Scale (CSSR-S).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jul 2012
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Long term follow-up planned |
No
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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 |
United States: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
0
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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) |
5
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrolled participants (par.) were aged 12 years to less than 18 years with partial onset seizures or Lennox-Gastaut syndrome (LGS), and were required to be on at least 1 but not more than 3 anti-epileptic therapies without achieving complete control of their seizures. | ||||||||||
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Pre-assignment
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Screening details |
A total of 5 par. who met the eligibility criteria were assigned to Regimen A (>50 kilograms [kg]) or B (30 to <=50 kg) based on body weight and entered a 2-week Screening phase, followed by a dosing phase (up to 5 weeks). Upon completion of the dosing phase, par. either entered a follow-up phase or a separate extension study. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Ezogabine/Retigabine | ||||||||||
Arm description |
Participants received an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
ezogabine/retigabine
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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 |
Initial dose of 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Baseline characteristics reporting groups
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Reporting group title |
Ezogabine/Retigabine
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Reporting group description |
Participants received an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ezogabine/Retigabine
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Reporting group description |
Participants received an initial dose of ezogabine/retigabine 300 milligrams (mg) per day administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||
Subject analysis set title |
Regimen A: Ezogabine/Retigabine (E/R) 300 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants (par.) with a body weight of >50 kilograms (kg) received a starting dose of 300 milligrams per day (mg/day) ezogabine/retigabine administered as 100 mg immediate release (IR) tablets three times a day (TID) orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: E/R 300/450 mg then 600 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally.At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: E/R 300/450/ 600/750 mg then 900 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Par. with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. At week two (Day 14), par. received 450 mg/day administered as 150 mg IR tablets TID orally. At week 3 (Day 21), par. received 600 mg/day administered as 200 mg IR tablets TID orally. At week 4 (Day 28), par. received 750 mg/day administered as 250 mg IR tablets TID orally. At week 5 (Day 35), par. received 900 mg/day administered as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: Ezogabine/Retigabine 300 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: Ezogabine/Retigabine 300 mg, then 450 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an uptitrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: Ezogabine/Retigabine 300/450 mg, then 600 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: Ezogabine/Retigabine 300/450/600 mg, then 750 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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Subject analysis set title |
Regimen A: Ezogabine/Retigabine 300/450/600/750, then 900 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg, 600 mg, and 750 mg (as 150 mg IR, 200 mg IR, and 250 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 900 mg/day ezogabine/retigabine as 300 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval.
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End point title |
The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) following oral administration of ezogabine/retigabine [1] | ||||||||||||||||
End point description |
The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC[0-tau]). The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau). Pharmacokinetic Population: all participants in the All Subjects Population (defined as all participants who received at least one dose of study medication) for whom a pharmacokinetic sample was obtained and analyzed.
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End point type |
Primary
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End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
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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: No statistical analysis was conducted for this end point. |
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| Notes [2] - Pharmacokinetic Population [3] - Pharmacokinetic Population [4] - Pharmacokinetic Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Apparent clearance (CL/F) following oral administration of ezogabine/retigabine [5] | ||||||||||||||||
End point description |
Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.
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End point type |
Primary
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End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
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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: No statistical analysis was conducted for this end point. |
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| Notes [6] - Pharmacokinetic Population [7] - Pharmacokinetic Population [8] - Pharmacokinetic Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Maximum observed concentration (Cmax) and pre-dose (trough) concentration at the end of the dosing interval (Ctau) following oral administration of ezogabine/retigabine [9] | ||||||||||||||||||||||||
End point description |
Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.
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End point type |
Primary
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End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
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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: No statistical analysis was conducted for this end point.rmed. |
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| Notes [10] - Pharmacokinetic Population [11] - Pharmacokinetic Population [12] - Pharmacokinetic Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Apparent volume of distribution (Vd/F) following oral administration of ezogabine/retigabine [13] | ||||||||||||||||
End point description |
The volume of distribution (Vd/F) is defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution. “Not Applicable (NA)” data is presented as “99999".
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End point type |
Primary
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End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
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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: No statistical analysis was conducted for this end point. |
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| Notes [14] - Pharmacokinetic Population. Only those par. available at the specified time points were analyzed. [15] - Pharmacokinetic Population. Only those par. available at the specified time points were analyzed. [16] - Pharmacokinetic Population. Only those par. available at the specified time points were analyzed. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of participants with any adverse event (AE) | ||||||||||||||||||
End point description |
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. 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.
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End point type |
Secondary
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End point timeframe |
From the start of the first titration until follow-up (assessed up to 46 days)
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| Notes [17] - All Subjects Population: all participants who received at least one dose of study medication [18] - All Subjects Population: all participants who received at least one dose of study medication [19] - All Subjects Population: all participants who received at least one dose of study medication [20] - All Subjects Population: all participants who received at least one dose of study medication [21] - All Subjects Population: all participants who received at least one dose of study medication |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from baseline in albumin and total protein at Day 7 post each up-titration | ||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
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End point type |
Secondary
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End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
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| Notes [22] - All Subjects Population [23] - All Subjects Population [24] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change from baseline in alkaline phosphatase, alanine amino transferase, aspartate amino transferase, and gamma glutamyl Transferase at Day 7 post each up-titration | ||||||||||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
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End point type |
Secondary
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End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
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| Notes [25] - All Subjects Population [26] - All Subjects Population [27] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in direct bilirubin, total bilirubin, creatinine, and uric acid at Day 7 post each up-titration | ||||||||||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population. “Not Applicable (NA)” data is presented as “99999".
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End point type |
Secondary
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End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
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| Notes [28] - All Subjects Population [29] - All Subjects Population [30] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in calcium, chloride, carbon dioxide content/bicarbonate, glucose, potassium, sodium, inorganic phosphorus, and urea/blood urea nitrogen (BUN) at Day 7 post each up-titration | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population. “Not Applicable (NA)” data is presented as “99999".
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End point type |
Secondary
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End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
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| Notes [31] - All Subjects Population [32] - All Subjects Population [33] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils (total ANC [total absolute neutrophil count]), platelet count, and white blood cell count at Day 7 post each up-titration | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
| Notes [34] - All Subjects Population [35] - All Subjects Population [36] - All Subjects Population |
|||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from baseline in hemoglobin and mean corpuscle hemoglobin concentration at Day 7 post each up-titration | ||||||||||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [37] - All Subjects Population [38] - All Subjects Population [39] - All Subjects Population |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Change from baseline in hematocrit at Day 7 post each up-titration | ||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [40] - All Subjects Population. Only those participants available at the specified time point were analyzed [41] - All Subjects Population. Only those participants available at the specified time point were analyzed [42] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from baseline in mean corpuscle hemoglobin at Day 7 post each up-titration | ||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [43] - All Subjects Population. Only those participants available at the specified time point were analyzed [44] - All Subjects Population. Only those participants available at the specified time point were analyzed [45] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from baseline in mean corpuscle volume at Day 7 post each up-titration | ||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [46] - All Subjects Population. Only those participants available at the specified time point were analyzed [47] - All Subjects Population. Only those participants available at the specified time point were analyzed [48] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from baseline in red blood cell count at Day 7 post each up-titration | ||||||||||||||||
End point description |
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline (Screening), Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [49] - All Subjects Population. Only those participants available at the specified time point were analyzed [50] - All Subjects Population. Only those participants available at the specified time point were analyzed [51] - All Subjects Population. Only those participants available at the specified time point were analyzed |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with the indicated urinalysis parameter dipstick test results from Screening to Follow-up | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Urinalysis parameters analyzed included: urine occult blood (UOB), urine glucose (UG), urine ketones (UK), and urine protein (UP). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test provides results in a semi-quantitative manner, and results can be read as negative (Neg), Trace, and 80, indicating proportional concentrations in the urine sample. Urinalysis parameters were assessed at Titration 1 (T1; 300 mg/day), Titration 2 (T2; 450 mg/day), Titration 3 (T3; 600 mg/day), Titration 4 (T4; 750 mg/day), and Titration 5 (T5; 900 mg/day). Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X in the category titles). Different participants may have been analyzed at different time points and for different parameters, so the overall number of participants analyzed reflects everyone in the ASP.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [52] - All Subjects Population (ASP) [53] - All Subjects Population (ASP) [54] - All Subjects Population (ASP) [55] - All Subjects Population (ASP) [56] - All Subjects Population (ASP) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||
End point title |
Percent change from baseline in 28-day seizure frequency rate | ||||||||
End point description |
Participants or their caregivers recorded the number of seizures experienced by the participant, by seizure type (e.g., simple partial seizure [seizure that affects only a small region of the brain; consciousness is unaffected], complex partial seizure [seizure associated with unilateral cerebral hemisphere involvement and causing impairment of awareness or responsiveness], etc.), as well as by duration of episodes of innumerable seizure activity, in their daily diaries during all phases of this study. Percent change from baseline (BL) is defined as 100 * (rate in a given period minus the baseline rate) / (baseline rate). baseline seizures are defined as those seizures that occurred after Screening and before the start of the treatment. Post-baseline seizures are defined as those seizures that occurred from the start of the treatment until the start of Follow-up. Seizure frequency rate was computed as: 28 * (number of seizures during given period / number of days in given period).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)
|
||||||||
|
|||||||||
| Notes [57] - All Subjects Population. Only par. with BL and post-BL seizure measurements were included. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration (AUC [0-t]) for the n-acetyl metabolite of ezogabine/retigabine | ||||||||||||||||
End point description |
The area under the curve was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the plasma n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [58] - PK Population [59] - PK Population [60] - PK Population |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Pre-dose (trough) concentration at the end of the dosing interval (Ctau) for the n-acetyl metabolite of ezogabine/retigabine | ||||||||||||||||
End point description |
Ctau refers to the pre-dose (trough) concentration at the end of the dosing interval which is equivalent to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the Ctau for n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [61] - PK Population [62] - PK Population [63] - PK Population |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Time to maximum concentration (Tmax) following oral administration of ezogabine/retigabine | ||||||||||||||||
End point description |
Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma Tmax.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [64] - PK Population [65] - PK Population [66] - PK Population |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Plasma half life at steady state (t1/2) following oral administration of ezogabine/retigabine | ||||||||||||||||
End point description |
Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma t1/2. Steady-state t1/2 is derived as (Vd/F) / (CL/F), where Vd/F is defined as the apparent volume of distribution after extravascular (e.g., oral) administration, and CL/F is defined as the apparent clearance following oral dosing. “Not Applicable (NA)” data is presented as “99999".
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
|
||||||||||||||||
|
|||||||||||||||||
| Notes [67] - PK Population. Only those participants available at the indicated time point were analyzed. [68] - PK Population. Only those participants available at the indicated time point were analyzed. [69] - PK Population. Only those participants available at the indicated time point were analyzed. |
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal electrocardiogram (ECG) findings | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc intervals) was used. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). ECG parameters were assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose, and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. The number of participants with abnormal (Abn) clinically significant (CS) and not clinically significant (NCS) ECG findings was recorded. The investigator determined if an ECG finding was CS or NCS.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Screening) and Day 7 post up-titration, up to Day 35
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [70] - All Subjects Population. Only those par. available at the specified time points were analyzed. [71] - All Subjects Population. Only those par. available at the specified time points were analyzed. [72] - All Subjects Population. Only those par. available at the specified time points were analyzed. [73] - All Subjects Population. Only those par. available at the specified time points were analyzed. [74] - All Subjects Population. Only those par. available at the specified time points were analyzed. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Vital sign assessment included the measurement of systolic and diastolic blood pressure at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), Day 7 pre-dose, and 3 h post dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): Day 21 pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): Day 35 pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value. “Not Applicable (NA)” data is presented as “99999".
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Screening) and Day 7 post up-titration, up to Day 35
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [75] - All Subjects Population. Only those par. available at the specified time points were analyzed. [76] - All Subjects Population. Only those par. available at the specified time points were analyzed. [77] - All Subjects Population. Only those par. available at the specified time points were analyzed. [78] - All Subjects Population. Only those par. available at the specified time points were analyzed. [79] - All Subjects Population. Only those par. available at the specified time points were analyzed. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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End point title |
Change from Baseline in heart rate (HR) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Vital sign assessment included heart rate measurement and was assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value. “Not Applicable (NA)” data is presented as “99999".
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End point type |
Secondary
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End point timeframe |
Baseline (Screening) and Day 7 post up-titration, up to Day 35
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| Notes [80] - All Subjects Population. Only those par. available at the specified time points were analyzed. [81] - All Subjects Population. Only those par. available at the specified time points were analyzed. [82] - All Subjects Population. Only those par. available at the specified time points were analyzed. [83] - All Subjects Population. Only those par. available at the specified time points were analyzed. [84] - All Subjects Population. Only those par. available at the specified time points were analyzed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in post void residual ultrasound at Day 21 | ||||||||
End point description |
A post void residual (PVR) bladder ultrasound was carried out as a measure of bladder function. PVR was clinically indicated following the occurrence of adverse events relating to the lower urinary tract (e.g., micturition difficulties, including urinary hesitancy or urinary retention). These assessments were also repeated following drug withdrawal following such events. A prompt follow-up PVR was recommended if a high score was obtained from a participant on the Pediatric Lower Urinary Tract Symptom scale (the PLUTS scale is a clinician-rated scale used to assess lower urinary tract symptoms, including urinary retention) and if the clinician felt that the participant was at risk or had symptoms of urinary retention. PVR was measured at Day 7 of Titration 3 (600 mg/day). Baseline is defined as the Screening visit.
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End point type |
Secondary
|
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End point timeframe |
Screening and Day 7 of Titration 3 (Day 21)
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| Notes [85] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with the indicated neurological abnormality | ||||||||||||||||||||||||||||||||||||||||
End point description |
Abnormal Central Nervous System (CNS) symptoms were assessed by a full and brief neurological examination. A full neurological examination included assessment of mental status, cranial nerves, gait, coordination, sensation, speech/language, muscle strength, muscle tone, and reflexes. A brief neurological examination included assessment of mental status, cranial nerves, gait, coordination, reflexes, and speech/language. Neurological parameters assessed were memory impairment, impaired intellect, decreased attention, psychomotor slowing, decreased muscle strength, hypertonia, somnolence, right and left biceps, right and left brachioradialis, right and left knee, right and left ankle, and right and left planter response. Neurological examination was performed at Day 7 of Titration 3 (600 mg/day). “Not Applicable (NA)” data is presented as “99999".
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End point type |
Secondary
|
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End point timeframe |
Screening and Day 7 of Titration 3 (Day 21)
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| Notes [86] - All Subjects Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse event data, volunteered by the participant, discovered by the investigator, or detected by other means, were collected from the start of study treatment until the Follow-up contact (maximum of 46 days).
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Adverse event reporting additional description |
Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, compromised of all participants who received at least one dose of study medication.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
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Reporting groups
|
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Reporting group title |
Regimen A: Ezogabine/Retigabine 300 mg
|
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Reporting group description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administerd as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. The TID dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regimen A: Ezogabine/Retigabine 300 mg, then 450 mg
|
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Reporting group description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants then received an up-titrated dose of 450 mg/day ezogabine/retigabine as 150 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regimen A: Ezogabine/Retigabine 300/450 mg, then 600 mg
|
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Reporting group description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine administered as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received an up-titrated dose of 450 mg/day ezogabine/retigabine (as 150 mg IR tablets TID orally) initially, then received an up-titrated dose of 600 mg/day ezogabine/retigabine as 200 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regimen A: Ezogabine/Retigabine 300/450/600 mg, then 750 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with a body weight of >50 kg received a starting dose of 300 mg/day ezogabine/retigabine as 100 mg IR tablets TID orally and underwent weekly up-titration at a frequency of no more than once per week. These participants received up-titrated doses of ezogabine/retigabine 450 mg and 600 mg (as 150 mg IR and 200 mg IR tablets, respectively, TID orally) initially, then received an up-titrated dose of 750 mg/day ezogabine/retigabine as 250 mg IR tablets TID orally. The TID daily dosing regimen was administered at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Regimen A: Ezogabine/Retigabine 300/450/600/750, then 900 mg
|
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Reporting group description |
Participants received an initial dose of ezogabine/retigabine 300 mg/day administered as 100 mg IR tablets TID orally and underwent weekly up-titration at Weeks 1, 3, and 5. Dose titration occurred no more than once per week, with participants receiving up-titrated daily doses of 450 mg (150 mg TID), 600 mg (200 mg TID), 750 mg (250 mg TID), and 900 mg (300 mg TID) at an 8-hour dosing interval or a 6-, 6-, 12-hour dosing interval. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
30 Jun 2011 |
Amendment No. 1: Addition of microsampling technique for pediatric volume assay validation and change of Sponsor IND holder. |
||
10 Oct 2012 |
Amendment No. 2: Clarification of exclusion criteria, laboratory parameters; and removal of urine PK.
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
