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Clinical Trial Results:
An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults with Partial-Onset Seizures.

Summary
EudraCT number	2009-017744-14
Trial protocol	NL DE ES FR BE DK IT BG PL
Global end of trial date	04 Dec 2012

Results information
Results version number	v1(current)
This version publication date	28 Dec 2016
First version publication date	28 Dec 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

113905

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Mar 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Dec 2012

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of retigabine immediate release (IR) as adjunctive therapy to each of the following specified monotherapy AED treatments: carbamazepine/ oxcarbazepine, lamotrigine, levetiracetam or valproic acid in subjects with partial-onset seizures (POS) using a flexible dosing regimen.

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jul 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

Bulgaria: 39

Country: Number of subjects enrolled

Denmark: 1

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 15

Country: Number of subjects enrolled

Italy: 29

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Poland: 6

Country: Number of subjects enrolled

Russian Federation: 67

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Thailand: 13

Country: Number of subjects enrolled

Ukraine: 23

Worldwide total number of subjects

203

EEA total number of subjects

100

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

191

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study 113905 was an open-label, multi-center, multi-country study of retigabine using a flexible dosing regimen in adult participants (par.) (>=18 years old) with partial-onset seizures. Since this was an open-label study, hypothesis testing was not performed. The focus of the analysis was on descriptive statistics.

Screening details

Eligible par. must have been taking one of the following antiepileptic drug treatments: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam, or valproic acid and required to have had at least 4 partial seizures during the 8-wk BL Phase and must have been receiving a stable dose of 1 of the prespecified monotherapy antiepileptic drug treatments.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

RTG flexible dose plus C/O

Arm description

Along with concurrent carbamazepine/oxcarbazepine (C/O), participants initiated treatment with retigabine (RTG) immediate release (IR) at 150 milligrams per day (mg/day) (50 mg thrice a day [TID]) and titrated to 600 mg/day (200 mg/day TID) over a 4-week Titration Phase. This was followed by a 16-week Flexible Dose Evaluation Phase, during which the dose could be increased or decreased on a weekly basis between 50 and 150 mg/day, depending on efficacy and tolerability, with the total dose staying between 300 and 1200 mg/day. Participants who were unable to tolerate a minimum dose of 300 mg/day were discontinued from the study.

Arm type

Experimental

Investigational medicinal product name

GW582892 (Retigabine IR) 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 50 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 100 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 200 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 300 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 400 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

RTG flexible dose plus lamotrigine

Arm description

Along with concurrent lamotrigine, participants initiated treatment with RTG IR at 150 mg/day (50 mg TID) and titrated to 600 mg/day (200 mg/day TID) over a 4-week Titration Phase. This was followed by a 16-week Flexible Dose Evaluation Phase, during which the dose could be increased or decreased on a weekly basis between 50 and 150 mg/day, depending on efficacy and tolerability, with the total dose staying between 300 and 1200 mg/day. Participants who were unable to tolerate a minimum dose of 300 mg/day were discontinued from the study.

Arm type

Experimental

Investigational medicinal product name

GW582892 (Retigabine IR) 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 50 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 100 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 200 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 300 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 400 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

RTG flexible dose plus levetiracetam

Arm description

Along with concurrent leveteracetam, participants initiated treatment with RTG IR at 150 mg/day (50 mg TID) and titrated to 600 mg/day (200 mg/day TID) over a 4-week Titration Phase. This was followed by a 16-week Flexible Dose Evaluation Phase, during which the dose could be increased or decreased on a weekly basis between 50 and 150 mg/day, depending on efficacy and tolerability, with the total dose staying between 300 and 1200 mg/day. Participants who were unable to tolerate a minimum dose of 300 mg/day were discontinued from the study.

Arm type

Experimental

Investigational medicinal product name

GW582892 (Retigabine IR) 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 50 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 100 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 200 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 300 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 400 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

RTG flexible dose plus valproic acid

Arm description

Along with concurrent valproic acid, participants initiated treatment with RTG IR at 150 mg/day (50 mg TID) and titrated to 600 mg/day (200 mg/day TID) over a 4-week Titration Phase. This was followed by a 16-week Flexible Dose Evaluation Phase, during which the dose could be increased or decreased on a weekly basis between 50 and 150 mg/day, depending on efficacy and tolerability, with the total dose staying between 300 and 1200 mg/day. Participants who were unable to tolerate a minimum dose of 300 mg/day were discontinued from the study.

Arm type

Experimental

Investigational medicinal product name

GW582892 (Retigabine IR) 50 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 50 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 100 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 200 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 300 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Investigational medicinal product name

GW582892 (Retigabine IR) 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GW582892 400 mg tablets were administered orally to maintain dosage between 300 to 1200 mg/day

Number of subjects in period 1	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Started	56	51	44	52
Completed	38	38	25	42
Not completed	18	13	19	10
Consent withdrawn by subject	4	2	4	3
Physician decision	-	1	1	-
Adverse event, non-fatal	12	8	11	4
Lost to follow-up	-	-	1	2
Lack of efficacy	1	2	2	1
Protocol deviation	1	-	-	-

Baseline characteristics

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Reporting group title

RTG flexible dose plus C/O

Reporting group description

Reporting group title

RTG flexible dose plus lamotrigine

Reporting group description

Reporting group title

RTG flexible dose plus levetiracetam

Reporting group description

Reporting group title

RTG flexible dose plus valproic acid

Reporting group description

Reporting group values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid	Total
Number of subjects	56	51	44	52
Age categorical
Units: Subjects
Age continuous
Baseline (BL) data were collected in members of the Safety Population (Pop), comprised of those participants (par.) who took at least one dose of RTG.
Units: years
arithmetic mean (standard deviation)	40.6 ( 14.99 )	38.2 ( 11.91 )	37 ( 14.94 )	40.3 ( 14.05 )	-
Gender categorical
Baseline data were collected in members of the Safety Population, comprised of those participants who took at least one dose of RTG.
Units: Subjects
Female	33	26	25	26	110
Male	23	25	19	26	93
Race/Ethnicity, Customized
Baseline data were collected in members of the Safety Population, comprised of those participants who took at least one dose of RTG.
Units: Subjects
Asian - Central/South Asian Heritage	1	1	0	0	2
Asian - South East Asian Heritage	0	5	5	3	13
White - White/Caucasian/European	55	45	39	49	188

End points

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Reporting group title

RTG flexible dose plus C/O

Reporting group description

Reporting group title

RTG flexible dose plus lamotrigine

Reporting group description

Reporting group title

RTG flexible dose plus levetiracetam

Reporting group description

Reporting group title

RTG flexible dose plus valproic acid

Reporting group description

Primary: Number of participants with a >=50% reduction in partial-onset seizure (POS) frequency from Baseline

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End point title

Number of participants with a >=50% reduction in partial-onset seizure (POS) frequency from Baseline ^[1]

End point description

The number of participants experiencing a >=50% reduction from Baseline (BL) in POS frequency during the Treatment Phase (TP) (i.e., Titration Phase and Flexible Dose Evaluation [FDE] Phase) was measured. A POS has its onset in a limited area on one side of the brain. POSs may remain limited or may spread to involve both sides of the brain. For both the Baseline Phase and the TP, seizure frequency was calculated as a 28-day rate using the following formula: 28 x {[(number of countable partial seizures in Phase) + (10 x number of days with innumerable seizures in Phase) + (number of occurrences of status epilepticus in Phase)] / number of applicable days in the Phase}, where all days in the Phase are considered applicable (including days with 0 seizures), except for days on which the participant failed to complete the Seizure Diary. >= 50% reduction from BL is calculated as 100 x (28-day partial seizure rate [PSR] for the TP - 28-day PSR for the BL Phase) / 28-day PSR for the BL Phase.

End point type

Primary

End point timeframe

From Baseline through Week 20 (Day 140)/Early Withdrawal

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: Since this was an open-label study, hypothesis testing was not performed. The focus of the analysis was on descriptive statistics.

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[2]	50 ^[3]	44 ^[4]	51 ^[5]
Units: participants	22	16	22	29

Notes
[2] - Intent-To-Treat (ITT) Pop: par. in the Safety Pop who provided at >= 1 post-BL efficacy assessment
[3] - ITT Population
[4] - ITT Population
[5] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated reduction or increase from Baseline in partial-onset seizure frequency

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End point title

Number of participants with the indicated reduction or increase from Baseline in partial-onset seizure frequency

End point description

Participants were assessed for the percent change from Baseline in seizure frequency; changes were categorized as Any Decrease (>0 to 25%, 25 to <50%, 50 to 75%, >75 to 100%) or No Change or Any Increase (>25%, 0 to 25%). A partial-onset seizure is a seizure that has its onset in a limited area on one side of the brain. Partial-onset seizures may remain limited or may spread to involve both sides of the brain.

End point type

Secondary

End point timeframe

From Baseline through Week 20 (Day 140)/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[6]	50 ^[7]	44 ^[8]	51 ^[9]
Units: participants
Any decrease	43	43	36	44
>0 to <25% decrease	16	10	6	7
25 to <50% decrease	5	17	8	8
50 to 75% decrease	10	8	14	17
>75 to 100% decrease	12	8	8	12
No change or any increase	12	7	8	7
>25% increase	10	4	5	6
0 to 25% increase	2	3	3	1

Notes
[6] - ITT Population
[7] - ITT Population
[8] - ITT Population
[9] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with a >=25%, >=75%, or 100% reduction in partial-onset seizure frequency from Baseline

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End point title

Number of participants with a >=25%, >=75%, or 100% reduction in partial-onset seizure frequency from Baseline

End point description

The number of participants experiencing a >=25%, >=75%, and 100% reduction from Baseline in partial-onset seizure frequency during the Treatment Phase (TP) (i.e., Titration Phase and Flexible Dose Evaluation [FDE] Phase) was measured. A partial-onset seizure is a seizure that has its onset in a limited area on one side of the brain. Partial-onset seizures may remain limited or may spread to involve both sides of the brain.

End point type

Secondary

End point timeframe

From Baseline through Week 20 (Day 140)/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[10]	50 ^[11]	44 ^[12]	51 ^[13]
Units: participants
>=25%	27	33	30	37
>=75%	12	8	8	12
100%	0	2	1	2

Notes
[10] - ITT Population
[11] - ITT Population
[12] - ITT Population
[13] - ITT Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in partial-onset seizure frequency

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End point title

Percent change from Baseline in partial-onset seizure frequency

End point description

Percent change from Baseline was calculated as the difference in the partial-onset seizure frequency (Treatment Phase minus the Baseline Phase) divided by the Baseline Phase frequency, multiplied by 100. Negative values indicate reductions from Baseline. A partial-onset seizure is a seizure that has its onset in a limited area on one side of the brain. Partial-onset seizures may remain limited or may spread to involve both sides of the brain.

End point type

Secondary

End point timeframe

From Baseline through Week 20 (Day 140)/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[14]	50 ^[15]	44 ^[16]	51 ^[17]
Units: percent change
arithmetic mean (standard deviation)	-24.6 ( 55.25 )	-27.8 ( 59.97 )	-28.7 ( 80.27 )	-27.1 ( 102.1 )

Notes
[14] - ITT Population
[15] - ITT Population
[16] - ITT Population
[17] - ITT Population

No statistical analyses for this end point

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related worry

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End point title

Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related worry

End point description

Participants were asked the following question daily: "How would you rate your epilepsy-related worry over the last 24 hours?" The original possible responses were 0-10, with 0="No worry" and 10="Worst worry imaginable." However, in the summarization, "1" was added to each participant's daily response, changing the possible values to 1-11, so that there would be no possibility of the percent change from Baseline being undefined. Baseline and Treatment Phase averages were calculated for each participant. The denominators for these by-phase averages were the number of non-missing days for each variable and phase. The by-phase averages were used as follows in the calculation of percent change from Baseline for each participant: 100 x Treatment Phase average – Baseline Phase average) / Baseline Phase average. A negative percent change from Baseline indicates a reduction from Baseline.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[18]	50 ^[19]	39 ^[20]	48 ^[21]
Units: Percent change
arithmetic mean (standard deviation)	0.8 ( 45.6 )	-7.5 ( 29.53 )	-9.1 ( 36.76 )	-2 ( 73.16 )

Notes
[18] - ITT Population
[19] - ITT Population
[20] - ITT Population
[21] - ITT Population

No statistical analyses for this end point

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you needed to

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End point title

Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you needed to

End point description

Participants were asked the following question daily: "How would you rate the extent to which epilepsy limited your ability to do what you needed to do over the last 24 hours?" The original possible responses were 0-10, with 0="Not at all limited" and 10="Unable to do anything I needed to." However, in the summarization, "1" was added to each participant's daily response, changing the possible values to 1-11, so that there would be no possibility of the percent change from Baseline being undefined. Baseline and Treatment Phase averages were calculated for each participant. The denominators for these by-phase averages were the number of non-missing days for each variable and phase. The by-phase averages were used as follows in the calculation of percent change from Baseline for each participant: 100 x Treatment Phase average – Baseline Phase average) / Baseline Phase average. A negative percent change from Baseline indicates a reduction from Baseline.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[22]	50 ^[23]	40 ^[24]	48 ^[25]
Units: Percent change
arithmetic mean (standard deviation)	10.2 ( 83.8 )	-7.7 ( 25.24 )	2.5 ( 30.97 )	10.6 ( 98.84 )

Notes
[22] - ITT Population
[23] - ITT Population
[24] - ITT Population
[25] - ITT Population

No statistical analyses for this end point

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you wanted to

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End point title

Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you wanted to

End point description

Participants were asked the following question daily: "How would you rate the extent to which epilepsy limited your ability to do what you wanted to do over the last 24 hours?" The original possible responses were 0-10, with 0="Not at all limited" and 10="Unable to do anything I wanted to." However, in the summarization, "1" was added to each participant's daily response, changing the possible values to 1-11, so that there would be no possibility of the percent change from Baseline being undefined. Baseline and Treatment Phase averages were calculated for each participant. The denominators for these by-phase averages were the number of non-missing days for each variable and phase. The by-phase averages were used as follows in the calculation of percent change from Baseline for each participant: 100 x Treatment Phase average – Baseline Phase average) / Baseline Phase average. A negative percent change from Baseline indicates a reduction from Baseline.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	55 ^[26]	50 ^[27]	39 ^[28]	48 ^[29]
Units: Percent change
arithmetic mean (standard deviation)	6.3 ( 83.07 )	-5 ( 25.72 )	3.2 ( 36.94 )	7.1 ( 97.31 )

Notes
[26] - ITT Population
[27] - ITT Population
[28] - ITT Population
[29] - ITT Population

No statistical analyses for this end point

Secondary: Percent change from Baseline in functional status: percentage of days with no missed work or school time

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End point title

Percent change from Baseline in functional status: percentage of days with no missed work or school time

End point description

Participants were asked the following question daily: "Did you miss any time from work or school in the last 24 hours due to epilepsy?" Possible responses were Yes, No, and NA=Not Applicable (no planned work or school in the last 24 hours). The variable summarized is the percentage of days with no missed work or school. Baseline and Treatment Phase averages were calculated for each participant. The denominators for these by-phase averages were the number of non-missing days for each variable and phase. The by-phase averages were used as follows in the calculation of percent change from Baseline for each participant: 100 x Treatment Phase average – Baseline Phase average) / Baseline Phase average. A positive percent change from Baseline indicates a reduction from Baseline in missed work or school.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	34 ^[30]	39 ^[31]	31 ^[32]	29 ^[33]
Units: Percent change
arithmetic mean (standard deviation)	53.5 ( 295.57 )	4.9 ( 9.37 )	3.7 ( 29.33 )	4.5 ( 11.71 )

Notes
[30] - ITT Population
[31] - ITT Population
[32] - ITT Population
[33] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the Short Form 36 Health Survey, version 2 (SF-36v2) domain scores at Week 20/Early Withdrawal

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End point title

Change from Baseline in the Short Form 36 Health Survey, version 2 (SF-36v2) domain scores at Week 20/Early Withdrawal

End point description

The SF-36v2 health survey is a self-administered, generic, 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health). Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Positive changes from Baseline indicate improvement.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[34]	46 ^[35]	38 ^[36]	46 ^[37]
Units: Scores on a scale
arithmetic mean (standard deviation)
Physical Functioning	-0.54 ( 5.461 )	0.89 ( 6.665 )	-0.7 ( 4.974 )	0.46 ( 5.465 )
Role-Physical	-1.31 ( 9.563 )	1.04 ( 9.366 )	0.31 ( 10.958 )	1.87 ( 7.644 )
Bodily Pain	0.92 ( 10.315 )	0.62 ( 10.925 )	1.28 ( 8.571 )	2.81 ( 11.198 )
General Health	-0.35 ( 7.303 )	2.55 ( 7.24 )	0.68 ( 6.342 )	2.45 ( 7.749 )
Vitality	-2.94 ( 10.657 )	0.52 ( 9.722 )	0.47 ( 6.838 )	1.56 ( 8.318 )
Social Functioning	-1.83 ( 12.022 )	0.58 ( 11.063 )	1.84 ( 9.787 )	2.1 ( 10.107 )
Role-Emotional	-1.43 ( 13.224 )	1.07 ( 10.991 )	2.19 ( 9.258 )	4.36 ( 12.719 )
Mental Health	-2.04 ( 10.51 )	0.72 ( 9.48 )	2.48 ( 8.685 )	3.31 ( 10.636 )

Notes
[34] - ITT Population
[35] - ITT Population
[36] - ITT Population
[37] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal

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End point title

Change from Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal

End point description

The SF-36 v2 Health Survey is a self-administered, generic, 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The physical component summary (PCS) score is a summary score representing overall physical health, which is derived from the 8 domains. As with the domains, PCS scores range from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Positive changes from Baseline indicate improvement.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[38]	46 ^[39]	38 ^[40]	46 ^[41]
Units: Scores on a scale
arithmetic mean (standard deviation)	0.17 ( 5.202 )	1.22 ( 6.218 )	-0.58 ( 5.648 )	0.82 ( 4.525 )

Notes
[38] - ITT Population
[39] - ITT Population
[40] - ITT Population
[41] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal

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End point title

Change from Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal

End point description

The SF-36 v2 Health Survey is a self-administered, generic, 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The mental component summary (MCS) score is a summary score representing overall mental health, which is derived from the 8 domains. As with the domains, MCS scores range from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Positive changes from Baseline indicate improvement.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[42]	46 ^[43]	38 ^[44]	46 ^[45]
Units: Scores on a scale
arithmetic mean (standard deviation)	-2.59 ( 12.359 )	0.66 ( 10.149 )	2.75 ( 8.851 )	3.79 ( 10.206 )

Notes
[42] - ITT Population
[43] - ITT Population
[44] - ITT Population
[45] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated response for the epilepsy-related worry component of the Patient Global Impression of Change (PGI-C) Score

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End point title

Number of participants with the indicated response for the epilepsy-related worry component of the Patient Global Impression of Change (PGI-C) Score

End point description

The PGI-C questionnaire was to be completed by the participant. Participants were asked the following question: Compared to before you started this study, how would you rate your current epilepsy-related worry: Much better, Moderately better, A little better, Unchanged, A little worse, Moderately worse, Much worse?

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[46]	46 ^[47]	40 ^[48]	46 ^[49]
Units: participants
Much better	7	9	4	11
Moderately better	11	16	15	16
A little better	13	6	4	11
Unchanged	16	11	13	6
A little worse	5	2	4	0
Moderately worse	0	1	0	0
Much worse	1	1	0	2

Notes
[46] - ITT Population
[47] - ITT Population
[48] - ITT Population
[49] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the PGI-C Score: Epilepsy-related worry

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End point title

Change from Baseline in the PGI-C Score: Epilepsy-related worry

End point description

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[50]	46 ^[51]	40 ^[52]	46 ^[53]
Units: Scores on a scale
arithmetic mean (standard deviation)	3.1 ( 1.32 )	2.7 ( 1.44 )	3 ( 1.24 )	2.5 ( 1.38 )

Notes
[50] - ITT Population
[51] - ITT Population
[52] - ITT Population
[53] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated response for the current ability to do the things you need to do component of the PGI-C Score

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End point title

Number of participants with the indicated response for the current ability to do the things you need to do component of the PGI-C Score

End point description

The PGI-C questionnaire was to be completed by the participant. Participants were asked the following question: Compared to before you started this study, how would you rate your current ability to do the things you need to do: Much better, Moderately better, A little better, Unchanged, A little worse, Moderately worse, Much worse?

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[54]	46 ^[55]	40 ^[56]	46 ^[57]
Units: participants
Much better	5	9	6	10
Moderately better	13	11	9	14
A little better	10	6	6	9
Unchanged	19	17	17	11
A little worse	2	3	1	1
Moderately worse	2	0	0	0
Much worse	2	0	1	1

Notes
[54] - ITT Population
[55] - ITT Population
[56] - ITT Population
[57] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you need to do

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End point title

Change from Baseline in the PGI-C Score: Current ability to do the things you need to do

End point description

The PGI-C questionnaire was to be completed by the participant. Participants were asked the following question: Compared to before you started this study, how would you rate your current ability to do the things you need to do: Much better, Moderately better, A little better, Unchanged, A little worse, Moderately worse, Much worse? Rating scores are integers from 1 to 7, with 1=Much better and 7=Much worse.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[58]	46 ^[59]	40 ^[60]	46 ^[61]
Units: Scores on a scale
arithmetic mean (standard deviation)	3.3 ( 1.43 )	2.9 ( 1.29 )	3.1 ( 1.34 )	2.6 ( 1.32 )

Notes
[58] - ITT Population
[59] - ITT Population
[60] - ITT Population
[61] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with the indicated response for the current ability to do the things you want to do component of the PGI-C Score

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End point title

Number of participants with the indicated response for the current ability to do the things you want to do component of the PGI-C Score

End point description

The PGI-C questionnaire was to be completed by the participant. Participants were asked the following question: Compared to before you started this study, how would you rate your current ability to do the things you want to do: Much better, Moderately better, A little better, Unchanged, A little worse, Moderately worse, Much worse.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[62]	46 ^[63]	40 ^[64]	46 ^[65]
Units: participants
Much better	2	8	4	11
Moderately better	13	13	12	16
A little better	11	4	6	9
Unchanged	20	20	17	8
A little worse	3	1	1	1
Moderately worse	3	0	0	0
Much worse	1	0	0	1

Notes
[62] - ITT Population
[63] - ITT Population
[64] - ITT Population
[65] - ITT Population

No statistical analyses for this end point

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you want to do

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End point title

Change from Baseline in the PGI-C Score: Current ability to do the things you want to do

End point description

The PGI-C questionnaire was to be completed by the participant. Participants were asked the following question: Compared to before you started this study, how would you rate your current ability to do the things you want to do: Much better, Moderately better, A little better, Unchanged, A little worse, Moderately worse, Much worse? Rating scores are integers from 1 to 7, with 1=Much better and 7=Much worse.

End point type

Secondary

End point timeframe

Baseline through Week 20/Early Withdrawal

End point values	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Number of subjects analysed	53 ^[66]	46 ^[67]	40 ^[68]	46 ^[69]
Units: Scores on a scale
arithmetic mean (standard deviation)	3.4 ( 1.29 )	2.8 ( 1.23 )	3 ( 1.12 )	2.5 ( 1.3 )

Notes
[66] - ITT Population
[67] - ITT Population
[68] - ITT Population
[69] - ITT Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication through the end of the Follow-up Phase (up to Week 33). SAEs considered to be related to study participation were also to be collected prior to treatment.

Adverse event reporting additional description

SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who took at least one dose of investigational product.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

RTG flexible dose plus C/O

Reporting group description

Reporting group title

RTG flexible dose plus lamotrigine

Reporting group description

Reporting group title

RTG flexible dose plus levetiracetam

Reporting group description

Reporting group title

RTG flexible dose plus valproic acid

Reporting group description

Serious adverse events	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 56 (0.00%)	4 / 51 (7.84%)	4 / 44 (9.09%)	1 / 52 (1.92%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Femoral neck fracture
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertensive crisis
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrioventricular block second degree
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Convulsion
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Grand mal convulsion
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures with secondary generalization
subjects affected / exposed	0 / 56 (0.00%)	1 / 51 (1.96%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vestibular disorder
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	0 / 44 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
subjects affected / exposed	0 / 56 (0.00%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	RTG flexible dose plus C/O	RTG flexible dose plus lamotrigine	RTG flexible dose plus levetiracetam	RTG flexible dose plus valproic acid
Total subjects affected by non serious adverse events
subjects affected / exposed	39 / 56 (69.64%)	33 / 51 (64.71%)	23 / 44 (52.27%)	31 / 52 (59.62%)
Nervous system disorders
Dizziness
subjects affected / exposed	15 / 56 (26.79%)	15 / 51 (29.41%)	14 / 44 (31.82%)	9 / 52 (17.31%)
occurrences all number	32	20	20	10
Somnolence
subjects affected / exposed	11 / 56 (19.64%)	8 / 51 (15.69%)	7 / 44 (15.91%)	17 / 52 (32.69%)
occurrences all number	12	9	7	20
Disturbance in attention
subjects affected / exposed	3 / 56 (5.36%)	3 / 51 (5.88%)	0 / 44 (0.00%)	3 / 52 (5.77%)
occurrences all number	3	3	0	6
Headache
subjects affected / exposed	1 / 56 (1.79%)	4 / 51 (7.84%)	2 / 44 (4.55%)	2 / 52 (3.85%)
occurrences all number	1	4	2	2
Memory impairment
subjects affected / exposed	4 / 56 (7.14%)	1 / 51 (1.96%)	1 / 44 (2.27%)	2 / 52 (3.85%)
occurrences all number	5	1	1	2
Speech disorder
subjects affected / exposed	2 / 56 (3.57%)	4 / 51 (7.84%)	2 / 44 (4.55%)	0 / 52 (0.00%)
occurrences all number	2	5	2	0
Convulsion
subjects affected / exposed	1 / 56 (1.79%)	1 / 51 (1.96%)	1 / 44 (2.27%)	3 / 52 (5.77%)
occurrences all number	1	1	1	3
Ataxia
subjects affected / exposed	3 / 56 (5.36%)	0 / 51 (0.00%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences all number	5	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	6 / 56 (10.71%)	5 / 51 (9.80%)	5 / 44 (11.36%)	1 / 52 (1.92%)
occurrences all number	6	6	5	1
Asthenia
subjects affected / exposed	1 / 56 (1.79%)	2 / 51 (3.92%)	5 / 44 (11.36%)	4 / 52 (7.69%)
occurrences all number	2	2	6	6
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	5 / 56 (8.93%)	7 / 51 (13.73%)	3 / 44 (6.82%)	4 / 52 (7.69%)
occurrences all number	6	7	4	4
Eye disorders
Diplopia
subjects affected / exposed	3 / 56 (5.36%)	0 / 51 (0.00%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences all number	3	0	1	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 56 (3.57%)	4 / 51 (7.84%)	1 / 44 (2.27%)	0 / 52 (0.00%)
occurrences all number	2	5	1	0
Psychiatric disorders
Confusional state
subjects affected / exposed	3 / 56 (5.36%)	0 / 51 (0.00%)	3 / 44 (6.82%)	1 / 52 (1.92%)
occurrences all number	4	0	3	1
Renal and urinary disorders
Strangury
subjects affected / exposed	3 / 56 (5.36%)	0 / 51 (0.00%)	0 / 44 (0.00%)	0 / 52 (0.00%)
occurrences all number	3	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

24 May 2010

Addition of Health Outcome Assessments; PGI-C and SF-36v2, Clarification on timings of inclusion criteria no. 2, no. 4 and exclusion criteria no. 7, no. 8 and no. 11. Also ECG was added to Visit 5 (Week 12) and magnesium was added to blood chemistry analysis.

05 Apr 2011

Sponsor Information page including primary and back-up medical monitor details. To clarify end of study treatment and entry into the Open-Label, Extension study, Baseline seizure collection period, concurrent AED use, Visit 8 assessments, exclusion no. 1-Clarify history of generalized epilepsy, and benzodiazepine use during the Baseline phase. Withdrawal criteria amended to include increase in QTc >60 msec from Baseline. To amend visit windows from ±3 to ±5 days to provide greater flexibility for scheduling subjects appointments. Added procedures/assessments to be performed from end of the Titration Phase through to the Taper/Follow-Up Phase including assessments which needs to be performed prior to the scheduled final visit (Visit 7) in order to assess eligibility for the extension study, RTG113413. Re-estimation of sample size and AED subgroup targets and typos and punctuations were corrected.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults with Partial-Onset Seizures.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with a >=50% reduction in partial-onset seizure (POS) frequency from Baseline

Primary: Number of participants with a >=50% reduction in partial-onset seizure (POS) frequency from Baseline

Secondary: Number of participants with the indicated reduction or increase from Baseline in partial-onset seizure frequency

Secondary: Number of participants with the indicated reduction or increase from Baseline in partial-onset seizure frequency

Secondary: Number of participants with a >=25%, >=75%, or 100% reduction in partial-onset seizure frequency from Baseline

Secondary: Number of participants with a >=25%, >=75%, or 100% reduction in partial-onset seizure frequency from Baseline

Secondary: Percent change from Baseline in partial-onset seizure frequency

Secondary: Percent change from Baseline in partial-onset seizure frequency

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related worry

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related worry

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you needed to

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you needed to

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you wanted to

Secondary: Functional Status Diary (FSD): Percent change from Baseline in epilepsy-related limitation of ability to do what you wanted to

Secondary: Percent change from Baseline in functional status: percentage of days with no missed work or school time

Secondary: Percent change from Baseline in functional status: percentage of days with no missed work or school time

Secondary: Change from Baseline in the Short Form 36 Health Survey, version 2 (SF-36v2) domain scores at Week 20/Early Withdrawal

Secondary: Change from Baseline in the Short Form 36 Health Survey, version 2 (SF-36v2) domain scores at Week 20/Early Withdrawal

Secondary: Change from Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal

Secondary: Change from Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal

Secondary: Change from Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal

Secondary: Change from Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal

Secondary: Number of participants with the indicated response for the epilepsy-related worry component of the Patient Global Impression of Change (PGI-C) Score

Secondary: Number of participants with the indicated response for the epilepsy-related worry component of the Patient Global Impression of Change (PGI-C) Score

Secondary: Change from Baseline in the PGI-C Score: Epilepsy-related worry

Secondary: Change from Baseline in the PGI-C Score: Epilepsy-related worry

Secondary: Number of participants with the indicated response for the current ability to do the things you need to do component of the PGI-C Score

Secondary: Number of participants with the indicated response for the current ability to do the things you need to do component of the PGI-C Score

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you need to do

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you need to do

Secondary: Number of participants with the indicated response for the current ability to do the things you want to do component of the PGI-C Score

Secondary: Number of participants with the indicated response for the current ability to do the things you want to do component of the PGI-C Score

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you want to do

Secondary: Change from Baseline in the PGI-C Score: Current ability to do the things you want to do

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults with Partial-Onset Seizures.