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Clinical Trial Results:
A multicenter, open-label, long-term, safety, tolerability and efficacy study of retigabine in adult epilepsy patients with partial-onset seizures (Extension of Study VRX-RET-E22-302)

Summary
EudraCT number	2006-000956-42
Trial protocol	GB HU BE ES DE
Global end of trial date	24 May 2018

Results information
Results version number	v4(current)
This version publication date	01 Nov 2018
First version publication date	08 Apr 2018
Other versions	v1 , v2 , v3
Version creation reason

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

VRX-RET-E22-304

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

25 Sep 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 May 2018

Was the trial ended prematurely?

Yes

Main objective of the trial

Main objective of the trial: To evaluate the safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy participants with partial-onset seizures, who completed the double-blind Study VRX-RET-E22-302

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Jul 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

12 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

France: 9

Country: Number of subjects enrolled

Germany: 41

Country: Number of subjects enrolled

Hungary: 11

Country: Number of subjects enrolled

Israel: 29

Country: Number of subjects enrolled

Poland: 70

Country: Number of subjects enrolled

Russian Federation: 48

Country: Number of subjects enrolled

South Africa: 43

Country: Number of subjects enrolled

Spain: 37

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Ukraine: 45

Country: Number of subjects enrolled

United States: 1

Worldwide total number of subjects

376

EEA total number of subjects

183

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)

374

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This was a multi-center, open-label, long-term, safety, tolerability and efficacy study involving 57 study sites in 13 countries (Australia, Belgium, France, Germany, Hungary, Israel, Poland, Russia, South Africa, Spain, Ukraine, the United Kingdom and the United States).

Screening details

A total of 376 adult epilepsy participants with partial-onset seizures who completed the parent study (VRX-RET-E22-302 [NCT00235755) entered this open label extension (OLE) study.

Period 1 title

Primary reporting phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Retigabine

Arm description

Eligible participants entered a 4-week transition phase of the double-blind parent study (study VRX-RET-E22-302), in which their dose of retigabine was titrated to or maintained at 300 milligrams (mg) three times daily (900 mg per day). Upon completion of the Transition phase of the parent study, participants enrolled into the extension study (RTG115097). Once enrolled in the OLE, doses were adjusted within the range of 600 mg to 1200 mg per day as an adjunct therapy to their ongoing antiepileptic drugs (AEDs) with or without vagal nerve stimulation (VNS) up to 121 months.

Arm type

Experimental

Investigational medicinal product name

Retigabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Retigabine was supplied as 50, 100 and 300 mg film coated tablets. Participants received retigabine dose of 300 mg three times daily (900 mg per day) a 4-week transition phase. Once enrolled in the OLE, doses were adjusted within the range of 600 mg to 1200 mg per day as an adjunct therapy to their ongoing AEDs with or without VNS up to 120 months.

Number of subjects in period 1	Retigabine
Started	376
Completed	30
Not completed	346
Adverse event, serious fatal	5
Physician decision	2
Request of the sponsor	19
Due to pigmentation risk concerns	2
Persistent ALT/AST above 3 times the ULN	3
Participant request	2
Termination of study at sponsor request	3
Discontinuation of study	1
Missing	1
ALT/AST levels above 5 times the ULN	3
Consent withdrawn by subject	97
Change in participant medical condition	3
Ongoing SAE from parent study	1
Participant passed away	1
Failed to return	8
Adverse event, non-fatal	96
Participant request unrelated to study	2
Pregnancy	3
Ministry of Health decision	25
Participant Immigrated to New Zealand	1
Unknown	1
Participant retired the informed consent	1
Lack of efficacy	56
Protocol deviation	10

Period 2 title

Safety follow-up continuation phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Safety follow-up continuation phase (SFUCP)

Arm description

Participants who withdraw from retigabine and who had retinal pigmentation or unexplained vision loss, pigmentation of non-retinal ocular tissue or discoloration of nails, lips, skin or mucosa entered the SFUCP. During the SFUCP, participants underwent 6-monthly comprehensive eye examinations and/or skin assessments by the investigator, ophthalmologist, retinal specialist or dermatologist as appropriate. Participants were followed up in the SFUCP until the dermatology/ophthalmology finding(s) either resolved or stabilized. Stabilization was defined in the protocol as no changes on two consecutive 6-monthly assessments over at least 12 months after discontinuation of retigabine.

Arm type

Experimental

Investigational medicinal product name

Retigabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2	Safety follow-up continuation phase (SFUCP)
Started	26
Completed	13
Not completed	13
Adverse event, serious fatal	1
Consent withdrawn by subject	5
Missing SFUCP disposition information	5
Study Closed/Terminated	2

Baseline characteristics

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Reporting group title

Retigabine

Reporting group description

Reporting group values	Retigabine	Total
Number of subjects	376
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	37.0 ± 11.85	-
Gender categorical
Units: Subjects
Female	195	195
Male	181	181
Race/Ethnicity, Customized
Units: Subjects
Caucasian	360	360
African-American (Black)	3	3
Asian	3	3
Unknown	10	10

End points

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Reporting group title

Retigabine

Reporting group description

Reporting group title

Safety follow-up continuation phase (SFUCP)

Reporting group description

Primary: Number of participants with treatment emergent adverse events (TEAEs) and Serious adverse events (TESAEs)

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End point title

Number of participants with treatment emergent adverse events (TEAEs) and Serious adverse events (TESAEs) ^[1]

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. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations and is associated with impaired liver function. TEAEs refer to an AE for which the onset was on or after Retigabine dose in this study and on or before 30 days after the last Retigabine dose date. AEs that started in the parent study that worsened in this study were also considered as TEAEs. Analysis was performed on the safety population which included participants who took at least 1 dose of study medication after being enrolled in this OLE study.

End point type

Primary

End point timeframe

Up to 122 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[2]
Units: Participants
Any TEAE	324
Any TESAE	78

Notes
[2] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with TEAEs leading to treatment discontinuation (disc.)

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End point title

Number of participants with TEAEs leading to treatment discontinuation (disc.) ^[3]

End point description

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A summary of participants with treatment emergent AEs leading to treatment disc. up to 122 months have been presented.

End point type

Primary

End point timeframe

Up to 122 months

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[4]
Units: Participants
Participants	115

Notes
[4] - Safety Population

No statistical analyses for this end point

Primary: Kaplan-Meier estimate of the Probability of disc. from Study Drug

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End point title

Kaplan-Meier estimate of the Probability of disc. from Study Drug ^[5]

End point description

Kaplan-Meier estimate of the probability of disc. at the specified time for all participants is presented. The time frame of premature study disc. was defined as the time from the day of first the study medication to the time of withdrawal from study drug. For those who had a taper dose start date, the time of withdrawal was the day before the start of taper dose. Participants who switched to commercial product were censored at the last dose of study drug (excluding taper). All participants who withdrew from the study/treatment prematurely but did not switch to commercial product were counted as an event. Number of participants continuing on retigabine at each time of withdrawal were analyzed (represented by n=x in the category titles).

End point type

Primary

End point timeframe

Up to 122 months

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[6]
Units: Percentage Probability of disc.
number (not applicable)
Day 0, n=374	0.5
Day 1, n=371	1.3
Day 2, n=369	1.9
Day 3, n=368	2.1
Day 4, n=367	2.4
Day 5, n=366	2.7
Day 6, n=365	2.9
Day 11, n=364	3.2
Day 13, n=363	3.5
Day 14, n=362	3.7
Day 16, n=361	4.0
Day 21, n=360	4.3
Day 22, n=359	4.5
Day 27, n=356	5.3
Day 28, n=350	6.9
Day 29, n=348	7.4
Day 30, n=344	8.5
Day 32, n=343	8.8
Day 35, n=341	9.3
Day 40, n=340	9.6
Day 41, n=339	9.8
Day 42, n=338	10.1
Day 45, n=337	10.4
Day 50, n=336	10.6
Day 56, n=335	10.9
Day 61, n=334	11.2
Day 62, n=333	11.4
Day 63, n=331	12.0
Day 71, n=330	12.2
Day 77, n=329	12.5
Day 82, n=328	12.8
Day 85, n=326	13.3
Day 86, n=325	13.6
Day 88, n=324	13.8
Day 90, n=322	14.4
Day 91, n=316	16.0
Day 92, n=313	16.8
Day 94, n=312	17.0
Day 95, n=310	17.6
Day 99, n=309	17.8
Day 104, n=308	18.1
Day 105, n=307	18.4
Day 107, n=306	18.6
Day 110, n=305	18.9
Day 112, n=303	19.4
Day 118, n=302	19.7
Day 121, n=300	20.2
Day 122, n=299	20.5
Day 126, n=298	20.7
Day 132, n=297	21.0
Day 134, n=296	21.3
Day 135, n=295	21.5
Day 138, n=294	21.8
Day 139, n=293	22.1
Day 141, n=292	22.3
Day 152, n=291	22.6
Day 155, n=290	22.9
Day 161, n=289	23.1
Day 164, n=288	23.4
Day 172, n=287	23.7
Day 176, n=286	23.9
Day 179, n=282	25.0
Day 180, n=278	26.1
Day 181, n=275	26.9
Day 182, n=273	27.4
Day 183, n=272	27.7
Day 184, n=271	27.9
Day 187, n=270	28.2
Day 188, n=269	28.5
Day 189, n=268	28.7
Day 192, n=267	29.0
Day 195, n=265	29.5
Day 198, n=264	29.8
Day 199, n=263	30.1
Day 204, n=262	30.3
Day 214, n=261	30.6
Day 216, n=260	30.9
Day 218, n=259	31.1
Day 221, n=258	31.4
Day 228, n=257	31.6
Day 231, n=256	31.9
Day 233, n=255	32.2
Day 235, n=254	32.4
Day 236, n=253	32.7
Day 237, n=251	33.2
Day 252, n=250	33.5
Day 260, n=249	33.8
Day 264, n=248	34.0
Day 265, n=247	34.3
Day 269, n=246	34.6
Day 270, n=245	34.8
Day 272, n=240	36.2
Day 274, n=239	36.4
Day 275, n=238	36.7
Day 276, n=236	37.2
Day 278, n=235	37.5
Day 279, n=234	37.8
Day 292, n=233	38.0
Day 299, n=231	38.6
Day 301, n=230	38.8
Day 310, n=229	39.1
Day 315, n=228	39.4
Day 316, n=227	39.6
Day 317, n=226	39.9
Day 322, n=225	40.2
Day 325, n=224	40.4
Day 339, n=223	40.7
Day 351, n=222	41.0
Day 357, n=221	41.2
Day 358, n=219	41.8
Day 363, n=218	42.0
Day 372, n=217	42.3
Day 375, n=216	42.6
Day 377, n=215	42.8
Day 416, n=214	43.1
Day 419, n=213	43.4
Day 425, n=212	43.6
Day 429, n=211	43.9
Day 437, n=210	44.1
Day 447, n=209	44.4
Day 455, n=208	44.7
Day 458, n=207	44.9
Day 460, n=206	45.2
Day 461, n=205	45.5
Day 478, n=204	45.7
Day 480, n=203	46.0
Day 482, n=202	46.3
Day 485, n=200	46.8
Day 492, n=197	47.6
Day 493, n=196	47.9
Day 497, n=194	48.4
Day 498, n=193	48.7
Day 501, n=192	48.9
Day 523, n=191	49.2
Day 525, n=190	49.5
Day 534, n=189	49.7
Day 536, n=188	50.0
Day 541, n=187	50.3
Day 553, n=186	50.5
Day 556, n=185	50.8
Day 587, n=184	51.1
Day 593, n=183	51.3
Day 594, n=182	51.6
Day 596, n=181	51.9
Day 601, n=180	52.1
Day 602, n=178	52.7
Day 610, n=177	52.9
Day 612, n=176	53.2
Day 617, n=175	53.5
Day 618, n=174	53.7
Day 632, n=173	54.0
Day 635, n=172	54.3
Day 669, n=171	54.5
Day 676, n=170	54.8
Day 678, n=169	55.1
Day 685, n=168	55.3
Day 700, n=167	55.6
Day 702, n=165	56.1
Day 703, n=164	56.4
Day 707, n=163	56.6
Day 714, n=162	56.9
Day 719, n=161	57.2
Day 720, n=160	57.4
Day 721, n=159	57.7
Day 724, n=158	58.0
Day 729, n=157	58.2
Day 760, n=156	58.5
Day 775, n=155	58.8
Day 777, n=154	59.0
Day 778, n=153	59.3
Day 779, n=152	59.6
Day 781, n=151	59.8
Day 796, n=150	60.1
Day 803, n=149	60.4
Day 818, n=148	60.6
Day 835, n=147	60.9
Day 840, n=146	61.2
Day 841, n=144	61.7
Day 842, n=143	62.0
Day 844, n=142	62.2
Day 845, n=141	62.5
Day 855, n=140	62.8
Day 856, n=139	63.0
Day 863, n=138	63.3
Day 870, n=137	63.6
Day 884, n=136	63.8
Day 893, n=135	64.1
Day 904, n=134	64.4
Day 924, n=133	64.6
Day 927, n=132	64.9
Day 938, n=131	65.2
Day 944, n=130	65.4
Day 947, n=128	66.0
Day 952, n=127	66.2
Day 975, n=126	66.5
Day 980, n=125	66.8
Day 994, n=123	67.3
Day 1067, n=122	67.6
Day 1074, n=121	67.8
Day 1084, n=120	68.1
Day 1091, n=119	68.4
Day 1129, n=118	68.6
Day 1141, n=117	68.9
Day 1142, n=116	69.1
Day 1148, n=115	69.4
Day 1196, n=114	69.7
Day 1198, n=113	69.9
Day 1206, n=112	70.2
Day 1207, n=111	70.5
Day 1211, n=110	70.7
Day 1221, n=109	71.0
Day 1231, n=108	71.3
Day 1299, n=107	71.5
Day 1316, n=106	71.8
Day 1322, n=105	72.1
Day 1389, n=104	72.3
Day 1413, n=103	72.6
Day 1436, n=102	72.6
Day 1446, n=101	72.9
Day 1450, n=100	73.1
Day 1451, n=99	73.1
Day 1452, n=98	73.4
Day 1521, n=97	73.7
Day 1541, n=96	73.7
Day 1545, n=95	73.7
Day 1547, n=94	74.0
Day 1563, n=93	74.0
Day 1567, n=92	74.2
Day 1569, n=91	74.5
Day 1589, n=90	74.5
Day 1618, n=89	74.5
Day 1619, n=88	74.5
Day 1623, n=87	74.5
Day 1632, n=86	74.5
Day 1656, n=85	74.5
Day 1660, n=84	74.5
Day 1668, n=83	74.8
Day 1672, n=82	75.1
Day 1676, n=81	75.4
Day 1680, n=80	75.4
Day 1694, n=79	75.4
Day 1697, n=78	75.4
Day 1752, n=77	75.4
Day 1756, n=76	75.8
Day 1760, n=75	75.8
Day 1792, n=74	76.1
Day 1802, n=73	76.1
Day 1807, n=72	76.1
Day 1814, n=71	76.4
Day 1819, n=70	76.4
Day 1836, n=69	76.4
Day 1849, n=68	76.4
Day 1855, n=67	76.4
Day 1887, n=66	76.4
Day 1895, n=65	76.8
Day 1904, n=64	76.8
Day 1919, n=63	76.8
Day 1920, n=62	77.1
Day 1926, n=61	77.5
Day 1928, n=60	77.5
Day 1929, n=59	77.9
Day 1931, n=58	78.3
Day 1937, n=57	78.3
Day 1951, n=56	78.6
Day 2005, n=55	79.0
Day 2037, n=54	79.4
Day 2044, n=53	79.4
Day 2092, n=52	79.8
Day 2157, n=51	80.2
Day 2161, n=50	80.6
Day 2162, n=49	81.0
Day 2182, n=48	81.3
Day 2183, n=47	81.7
Day 2184, n=46	82.1
Day 2227, n=45	82.5
Day 2281, n=44	82.9
Day 2283, n=43	83.3
Day 2285, n=42	83.7
Day 2296, n=41	83.7
Day 2317, n=40	84.1
Day 2380, n=39	84.5
Day 2395, n=37	85.3
Day 2400, n=36	85.7
Day 2405, n=35	86.1
Day 2408, n=34	86.5
Day 2415, n=33	86.9
Day 2443, n=32	86.9
Day 2525, n=31	87.3
Day 2533, n=30	87.7
Day 2537, n=29	88.1
Day 2639, n=28	88.5
Day 2664, n=27	88.9
Day 2772, n=26	89.3
Day 2793, n=25	89.7
Day 2829, n=24	90.1
Day 2870, n=23	90.6
Day 2884, n=22	91.0
Day 2973, n=21	91.4
Day 2975, n=20	91.8
Day 2998, n=19	92.2
Day 3101, n=18	92.6
Day 3118, n=17	93.0
Day 3137, n=16	93.4
Day 3144, n=15	93.8
Day 3147, n=14	94.3
Day 3185, n=13	94.7
Day 3220, n=11	95.5
Day 3231, n=10	95.9
Day 3243, n=9	96.3
Day 3246, n=8	96.7
Day 3276, n=7	97.1
Day 3277, n=6	97.5
Day 3285, n=5	97.9
Day 3318, n=4	98.4
Day 3360, n=3	98.8
Day 3483, n=2	99.2
Day 3582, n=1	99.6

Notes
[6] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in the supine and standing position

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End point title

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in the supine and standing position ^[7]

End point description

Vital sign measurements (supine and standing blood pressure ) were obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Evaluations of blood pressure were performed supine at each study visit, and again after the participant had been standing for approximately 2 minutes. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[8]
Units: Millimeters of mercury
arithmetic mean (standard deviation)
Supine DBP, Visit 1 (Month 1), n=358	0.4 ± 10.05
Supine DBP, Visit 2 (Month 3), n=328	0.3 ± 9.83
Supine DBP, Visit 3 (Month 6), n=287	-0.2 ± 10.19
Supine DBP, Visit 4 (Month 9), n=251	0.0 ± 11.09
Supine DBP, Visit 5 (Month 12), n=235	0.7 ± 10.79
Supine DBP, Visit 6 (Month 16), n=202	1.0 ± 10.02
Supine DBP, Visit 7 (Month 20), n=181	0.4 ± 10.03
Supine DBP, Visit 8 (Month 24), n=167	0.4 ± 10.63
Supine DBP, Visit 9 (Month 28), n=147	1.5 ± 10.62
Supine DBP, Visit 10 (Month 32), n=128	0.0 ± 10.42
Supine DBP, Visit 11 (Month 36), n=121	1.0 ± 10.65
Supine DBP,Visit 12 (Month 40), n=112	2.0 ± 10.37
Supine DBP, Visit 13 (Month 44), n=105	0.5 ± 9.54
Supine DBP, Visit 14 (Month 48), n=104	0.0 ± 10.30
Supine DBP, Visit 15 (Month 52), n=91	0.1 ± 11.10
Supine DBP, Visit 16 (Month 56), n=77	1.2 ± 9.68
Supine DBP, Visit 17 (Month 60), n=92	-1.0 ± 11.08
Supine DBP, Visit 18 (Month 64), n=58	1.6 ± 8.29
Supine DBP, Visit 19 (Month 68), n=53	0.6 ± 8.66
Supine DBP, Visit 20 (Month 72), n=61	1.3 ± 8.38
Supine DBP, Visit 21 (Month 76), n=43	3.2 ± 8.88
Supine DBP, Visit 22 (Month 80), n=37	1.8 ± 7.66
Supine DBP, Visit 23 (Month 84), n=32	-1.4 ± 8.64
Supine DBP, Visit 24 (Month 88), n=29	3.4 ± 8.83
Supine DBP, Visit 25 (Month 92), n=25	2.3 ± 7.29
Supine DBP, Visit 26 (Month 96), n=26	1.5 ± 10.10
Supine DBP, Visit 27 (Month 100), n=20	1.5 ± 8.42
Supine DBP, Visit 28 (Month 104), n=17	3.4 ± 10.56
Supine DBP, Visit 29 (Month 108), n=13	0.5 ± 6.74
Supine DBP, Visit 30 (Month 112), n=4	4.0 ± 7.30
Supine DBP, Visit 31 (Month 116), n=3	11.0 ± 7.55
Supine DBP, Visit 32 (Month 120), n=1	-2.0 ± 99999
Supine DBP, Follow up, n=267	1.3 ± 10.08
Standing DBP, Visit 1 (Month 1), n=357	0.6 ± 10.68
Standing DBP, Visit 2 (Month 3), n=328	0.2 ± 10.62
Standing DBP, Visit 3 (Month 6), n=287	-0.1 ± 10.21
Standing DBP, Visit 4 (Month 9), n=251	0.2 ± 10.14
Standing DBP, Visit 5 (Month 12), n=235	0.8 ± 10.17
Standing DBP, Visit 6 (Month 16), n=202	0.3 ± 10.16
Standing DBP, Visit 7 (Month 20), n=181	0.4 ± 9.51
Standing DBP, Visit 8 (Month 24), n=167	0.2 ± 9.83
Standing DBP, Visit 9 (Month 28), n=147	0.3 ± 10.00
Standing DBP, Visit 10 (Month 32), n=128	-0.6 ± 10.64
Standing DBP, Visit 11 (Month 36), n=121	0.9 ± 10.94
Standing DBP, Visit 12 (Month 40), n=111	1.4 ± 11.01
Standing DBP, Visit 13 (Month 44), n=105	-0.2 ± 10.76
Standing DBP, Visit 14 (Month 48), n=104	0.3 ± 10.35
Standing DBP, Visit 15 (Month 52), n=91	-1.5 ± 11.00
Standing DBP, Visit 16 (Month 56), n=77	-0.3 ± 10.40
Standing DBP, Visit 17 (Month 60), n=92	-1.5 ± 9.70
Standing DBP, Visit 18 (Month 64), n=58	0.5 ± 8.07
Standing DBP, Visit 19 (Month 68), n=53	0.0 ± 7.20
Standing DBP, Visit 20 (Month 72), n=61	0.3 ± 8.31
Standing DBP, Visit 21 (Month 76), n=43	1.4 ± 8.93
Standing DBP, Visit 22 (Month 80), n=37	0.3 ± 8.03
Standing DBP, Visit 23 (Month 84), n=32	-0.4 ± 7.98
Standing DBP, Visit 24 (Month 88), n=29	1.6 ± 8.38
Standing DBP, Visit 25 (Month 92), n=25	1.0 ± 7.33
Standing DBP, Visit 26 (Month 96), n=26	1.6 ± 9.20
Standing DBP, Visit 27 (Month 100), n=20	0.2 ± 10.48
Standing DBP, Visit 28 (Month 104), n=17	2.8 ± 11.65
Standing DBP, Visit 29 (Month 108), n=13	-0.5 ± 9.42
Standing DBP, Visit 30 (Month 112), n=4	1.3 ± 9.18
Standing DBP, Visit 31 (Month 116), n=3	8.0 ± 11.79
Standing DBP, Visit 32 (Month 120), n=1	-1.0 ± 99999
Standing DBP, Follow up, n=267	2.0 ± 10.57
Supine SBP, Visit 1 (Month 1), n=358	-0.2 ± 12.03
Supine SBP, Visit 2 (Month 3), n=328	-0.4 ± 12.09
Supine SBP, Visit 3 (Month 6), n=287	0.5 ± 13.53
Supine SBP, Visit 4 (Month 9), n=251	0.0 ± 15.32
Supine SBP, Visit 5 (Month 12), n=235	0.5 ± 12.99
Supine SBP, Visit 6 (Month 16), n=202	0.7 ± 14.39
Supine SBP, Visit 7 (Month 20), n=181	-0.5 ± 14.34
Supine SBP, Visit 8 (Month 24), n=167	-0.4 ± 14.11
Supine SBP, Visit 9 (Month 28), n=147	0.2 ± 13.78
Supine SBP, Visit 10 (Month 32), n=128	0.3 ± 13.60
Supine SBP, Visit 11 (Month 36), n=121	0.2 ± 14.90
Supine SBP, Visit 12 (Month 40), n=112	1.3 ± 13.90
Supine SBP, Visit 13 (Month 44), n=105	0.1 ± 11.28
Supine SBP, Visit 14 (Month 48), n=104	-1.1 ± 13.03
Supine SBP, Visit 15 (Month 52), n=91	-0.7 ± 14.05
Supine SBP, Visit 16 (Month 56), n=77	2.6 ± 13.41
Supine SBP, Visit 17 (Month 60), n=92	-0.2 ± 14.48
Supine SBP, Visit 18 (Month 64), n=58	1.8 ± 12.11
Supine SBP, Visit 19 (Month 68), n=53	1.1 ± 13.00
Supine SBP, Visit 20 (Month 72), n=61	2.5 ± 10.26
Supine SBP, Visit 21 (Month 76), n=43	4.4 ± 15.51
Supine SBP, Visit 22 (Month 80), n=37	2.3 ± 15.13
Supine SBP, Visit 23 (Month 84), n=32	1.1 ± 13.90
Supine SBP, Visit 24 (Month 88), n=29	2.7 ± 12.51
Supine SBP, Visit 25 (Month 92), n=25	2.8 ± 10.44
Supine SBP, Visit 26 (Month 96), n=26	2.9 ± 14.66
Supine SBP, Visit 27 (Month 100), n=20	2.6 ± 10.61
Supine SBP, Visit 28 (Month 104), n=17	5.8 ± 10.91
Supine SBP, Visit 29 (Month 108), n=13	-2.2 ± 8.68
Supine SBP, Visit 30 (Month 112), n=4	8.5 ± 6.95
Supine SBP, Visit 31 (Month 116), n=3	13.7 ± 4.93
Supine SBP, Visit 32 (Month 120), n=1	11.0 ± 99999
Supine SBP, Follow up, n=267	1.2 ± 14.15
Standing SBP, Visit 1 (Month 1), n=357	-1.2 ± 12.20
Standing SBP, Visit 2 (Month 3), n=328	-0.7 ± 13.30
Standing SBP, Visit 3 (Month 6), n=287	-0.2 ± 13.89
Standing SBP, Visit 4 (Month 9), n=251	-0.7 ± 15.10
Standing SBP, Visit 5 (Month 12), n=235	-0.7 ± 14.56
Standing SBP, Visit 6 (Month 16), n=202	-0.3 ± 14.09
Standing SBP, Visit 7 (Month 20), n=181	-0.8 ± 15.19
Standing SBP, Visit 8 (Month 24), n=167	-0.5 ± 15.35
Standing SBP, Visit 9 (Month 28), n=147	-0.3 ± 16.30
Standing SBP, Visit 10 (Month 32), n=128	-0.1 ± 15.06
Standing SBP, Visit 11 (Month 36), n=121	0.7 ± 15.51
Standing SBP, Visit 12 (Month 40), n=111	2.7 ± 14.21
Standing SBP, Visit 13 (Month 44), n=105	-1.3 ± 12.57
Standing SBP, Visit 14 (Month 48), n=104	-1.6 ± 14.67
Standing SBP, Visit 15 (Month 52), n=91	-1.2 ± 14.35
Standing SBP, Visit 16 (Month 56), n=77	0.9 ± 15.04
Standing SBP, Visit 17 (Month 60), n=92	-0.7 ± 14.92
Standing SBP, Visit 18 (Month 64), n= 58	0.6 ± 12.84
Standing SBP, Visit 19 (Month 68), n=53	0.2 ± 11.85
Standing SBP, Visit 20 (Month 72), n=61	0.5 ± 12.43
Standing SBP, Visit 21 (Month 76), n=43	3.5 ± 12.47
Standing SBP, Visit 22 (Month 80), n=37	0.9 ± 14.31
Standing SBP, Visit 23 (Month 84), n=32	-0.8 ± 14.85
Standing SBP, Visit 24 (Month 88), n=29	-0.6 ± 13.28
Standing SBP, Visit 25 (Month 92), n=25	-1.6 ± 10.49
Standing SBP, Visit 26 (Month 96), n=26	-0.2 ± 14.68
Standing SBP, Visit 27 (Month 100), n=20	0.0 ± 12.62
Standing SBP, Visit 28 (Month 104), n=17	2.9 ± 11.70
Standing SBP, Visit 29 (Month 108), n=13	-2.2 ± 10.58
Standing SBP, Visit 30 (Month 112), n=4	1.8 ± 9.60
Standing SBP, Visit 31 (Month 116), n=3	9.0 ± 1.00
Standing SBP, Visit 32 (Month 120), n=1	10.0 ± 99999
Standing SBP, Follow up, n=267	1.4 ± 14.59

Notes
[8] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in heart rate (HR) measurements in the supine and standing position

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End point title

Change from Baseline in heart rate (HR) measurements in the supine and standing position ^[9]

End point description

Vital sign measurement HR was obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Evaluations of HR was performed supine at each study visit, and again after the participant had been standing for approximately 2 minutes. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[10]
Units: Beats per minute
arithmetic mean (standard deviation)
Supine HR, Visit 1 (Month 1), n=358	-0.4 ± 9.89
Supine HR, Visit 2 (Month 3), n=328	-0.5 ± 9.93
Supine HR, Visit 3 (Month 6), n=287	0.1 ± 9.62
Supine HR, Visit 4 (Month 9), n=252	0.7 ± 9.69
Supine HR, Visit 5 (Month 12), n=235	0.0 ± 9.83
Supine HR, Visit 6 (Month 16), n=202	1.8 ± 10.56
Supine HR, Visit 7 (Month 20), n=181	2.3 ± 11.87
Supine HR, Visit 8 (Month 24), n=167	1.9 ± 10.28
Supine HR, Visit 9 (Month 28), n=147	2.7 ± 10.86
Supine HR, Visit 10 (Month 32), n=128	3.0 ± 10.50
Supine HR, Visit 11 (Month 36), n=121	0.8 ± 10.33
Supine HR, Visit 12 (Month 40), n=112	3.3 ± 11.20
Supine HR, Visit 13 (Month 44), n=105	1.8 ± 10.59
Supine HR, Visit 14 (Month 48), n=104	1.0 ± 10.78
Supine HR, Visit 15 (Month 52), n=91	2.0 ± 12.20
Supine HR, Visit 16 (Month 56), n=77	2.5 ± 10.70
Supine HR, Visit 17 (Month 60), n=92	0.9 ± 12.25
Supine HR, Visit 18 (Month 64), n=58	5.5 ± 10.44
Supine HR, Visit 19 (Month 68), n=53	2.4 ± 10.19
Supine HR, Visit 20 (Month 72), n=61	2.1 ± 12.23
Supine HR, Visit 21 (Month 76), n=43	2.8 ± 9.30
Supine HR, Visit 22 (Month 80), n=37	5.1 ± 10.13
Supine HR, Visit 23 (Month 84), n=32	3.5 ± 11.98
Supine HR, Visit 24 (Month 88), n=29	3.2 ± 13.66
Supine HR, Visit 25 (Month 92), n=25	3.9 ± 9.89
Supine HR, Visit 26 (Month 96), n=26	2.1 ± 10.37
Supine HR, Visit 27 (Month 100), n=20	3.1 ± 9.82
Supine HR, Visit 28 (Month 104), n=17	3.3 ± 8.62
Supine HR, Visit 29 (Month 108), n=13	0.5 ± 8.93
Supine HR, Visit 30 (Month 112), n=4	3.8 ± 12.84
Supine HR, Visit 31 (Month 116), n=3	7.7 ± 13.43
Supine HR, Visit 32 (Month 120), n=1	11.0 ± 99999
Supine HR, Follow up, n=267	2.1 ± 10.44
Standing HR, Visit 1 (Month 1), n=357	-0.1 ± 11.10
Standing HR, Visit 2 (Month 3), n=328	-0.2 ± 11.01
Standing HR, Visit 3 (Month 6), n=287	0.3 ± 10.39
Standing HR, Visit 4 (Month 9), n=252	1.7 ± 11.53
Standing HR, Visit 5 (Month 12), n=235	0.1 ± 11.06
Standing HR, Visit 6 (Month 16), n=202	1.6 ± 12.35
Standing HR, Visit 7 (Month 20), n=181	1.4 ± 12.71
Standing HR, Visit 8 (Month 24), n=167	1.9 ± 10.93
Standing HR, Visit 9 (Month 28), n=147	1.6 ± 11.25
Standing HR, Visit 10 (Month 32), n=128	2.2 ± 11.92
Standing HR, Visit 11 (Month 36), n=121	-0.6 ± 11.23
Standing HR, Visit 12 (Month 40), n=111	2.6 ± 12.94
Standing HR, Visit 13 (Month 44), n=105	2.8 ± 11.22
Standing HR, Visit 14 (Month 48), n=104	0.8 ± 11.81
Standing HR, Visit 15 (Month 52), n=91	3.1 ± 12.09
Standing HR, Visit 16 (Month 56), n=77	1.3 ± 12.12
Standing HR, Visit 17 (Month 60), n=92	0.6 ± 12.26
Standing HR, Visit 18 (Month 64), n=58	4.6 ± 12.09
Standing HR, Visit 19 (Month 68), n=52	1.3 ± 10.78
Standing HR, Visit 20 (Month 72), n=61	0.7 ± 13.45
Standing HR, Visit 21 (Month 76), n=43	0.3 ± 10.83
Standing HR, Visit 22 (Month 80), n=37	2.9 ± 10.96
Standing HR, Visit 23 (Month 84), n=32	2.3 ± 9.76
Standing HR, Visit 24 (Month 88), n=29	2.4 ± 10.64
Standing HR, Visit 25 (Month 92), n=25	3.6 ± 12.61
Standing HR, Visit 26 (Month 96), n=26	3.1 ± 12.01
Standing HR, Visit 27 (Month 100), n=20	5.2 ± 9.88
Syanding HR, Visit 28 (Month 104), n=17	6.2 ± 11.00
Standing HR, Visit 29 (Month 108), n=13	-0.2 ± 8.94
Standing HR, Visit 30 (Month 112), n=4	2.3 ± 12.84
Standing HR, Visit 31 (Month 116), n=3	7.3 ± 12.10
Standing HR, Visit 32 (Month 120), n=1	10.0 ± 99999
Standing HR, Follow up, n=267	2.2 ± 11.39

Notes
[10] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in body temperature

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End point title

Change from Baseline in body temperature ^[11]

End point description

Vital sign measurement temperature was obtained throughout the study at all visits during the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[12]
Units: Degree Celsius
arithmetic mean (standard deviation)
Body temperature, Visit 1 (Month 1), n=350	0.02 ± 0.386
Body temperature, Visit 2 (Month 3), n=318	0.02 ± 0.358
Body temperature, Visit 3 (Month 6), n=280	0.03 ± 0.384
Body temperature, Visit 4 (Month 9), n=244	0.00 ± 0.380
Body temperature, Visit 5 (Month 12), n=229	0.01 ± 0.392
Body temperature, Visit 6 (Month 16), n=197	0.02 ± 0.362
Body temperature, Visit 7 (Month 20), n=176	0.04 ± 0.381
Body temperature, Visit 8 (Month 24), n=161	0.02 ± 0.387
Body temperature, Visit 9 (Month 28), n=143	0.01 ± 0.407
Body temperature, Visit 10 (Month 32), n=125	0.02 ± 0.362
Body temperature, Visit 11 (Month 36), n=118	0.02 ± 0.385
Body temperature, Visit 12 (Month 40), n=109	0.01 ± 0.404
Body temperature, Visit 13 (Month 44), n=101	0.04 ± 0.387
Body temperature, Visit 14 (Month 48), n=100	0.05 ± 0.382
Body temperature, Visit 15 (Month 52), n=88	-0.02 ± 0.396
Body temperature, Visit 16 (Month 56), n=74	-0.01 ± 0.393
Body temperature, Visit 17 (Month 60), n=89	0.03 ± 0.391
Body temperature, Visit 18 (Month 64), n=58	-0.01 ± 0.306
Body temperature, Visit 19 (Month 68), n=53	0.05 ± 0.318
Body temperature, Visit 20 (Month 72), n=59	0.06 ± 0.373
Body temperature, Visit 21 (Month 76), n=42	0.06 ± 0.306
Body temperature, Visit 22 (Month 80), n=37	-0.04 ± 0.362
Body temperature, Visit 23 (Month 84), n=32	0.05 ± 0.324
Body temperature, Visit 24 (Month 88), n=29	-0.06 ± 0.313
Body temperature, Visit 25 (Month 92), n=25	0.00 ± 0.289
Body temperature, Visit 26 (Month 96), n=26	-0.10 ± 0.299
Body temperature, Visit 27 (Month 100), n=20	-0.03 ± 0.285
Body temperature, Visit 28 (Month 104), n=17	-0.02 ± 0.326
Body temperature, Visit 29 (Month 108), n=13	0.04 ± 0.275
Body temperature, Visit 30 (Month 112), n=4	-0.02 ± 0.126
Body temperature, Visit 31 (Month 116), n=3	-0.20 ± 0.200
Body temperature, Visit 32 (Month 120), n=1	0.10 ± 99999
Body temperature, Follow up, n=261	0.03 ± 0.397

Notes
[12] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in body weight

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End point title

Change from Baseline in body weight ^[13]

End point description

Weight in pounds or kilograms was measured in ordinary indoor clothing (without shoes) and was recorded at all study visits during the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[14]
Units: Kilograms
arithmetic mean (standard deviation)
Body weight, Visit 1 (Month 1), n=356	1.19 ± 3.125
Body weight, Visit 2 (Month 3), n=325	1.37 ± 3.630
Body weight, Visit 3 (Month 6), n=287	1.51 ± 4.528
Body weight, Visit 4 (Month 9), n=252	1.08 ± 5.068
Body weight, Visit 5 (Month 12), n=235	1.56 ± 4.764
Body weight, Visit 6 (Month 16), n=202	1.98 ± 5.382
Body weight, Visit 7 (Month 20), n=181	1.79 ± 5.762
Body weight, Visit 8 (Month 24), n=167	1.20 ± 6.571
Body weight, Visit 9 (Month 28), n=147	1.67 ± 6.101
Body weight, Visit 10 (Month 32), n=128	1.75 ± 7.103
Body weight, Visit 11 (Month 36), n=121	2.07 ± 7.151
Body weight, Visit 12 (Month 40), 112	2.12 ± 7.077
Body weight, Visit 13 (Month 44), n=105	1.09 ± 7.469
Body weight, Visit 14 (Month 48), n=104	1.08 ± 8.007
Body weight, Visit 15 (Month 52), n=91	0.66 ± 7.539
Body weight, Visit 16 (Month 56), n=77	0.71 ± 7.248
Body weight, Visit 17 (Month 60), n=91	1.31 ± 8.082
Body weight, Visit 18 (Month 64), n=58	1.32 ± 7.541
Body weight, Visit 19 (Month 68), n=53	1.49 ± 8.036
Body weight, Visit 20 (Month 72), n=61	1.65 ± 8.774
Body weight, Visit 21 (Month 76), n=43	1.71 ± 9.355
Body weight, Visit 22 (Month 80), n=37	2.30 ± 9.311
Body weight, Visit 23 (Month 84), n=32	2.00 ± 9.522
Body weight, Visit 24 (Month 88), n=29	1.12 ± 9.633
Body weight, Visit 25 (Month 92), n=25	0.83 ± 10.845
Body weight, Visit 26 (Month 96), n=26	0.12 ± 14.470
Body weight, Visit 27 (Month 100), n=20	1.57 ± 11.382
Body weight, Visit 28 (Month 104), n=17	1.62 ± 10.715
Body weight, Visit 29 (Month 108), n=13	2.32 ± 13.914
Body weight, Visit 30 (Month 112), n=4	4.85 ± 17.693
Body weight, Visit 31 (Month 116), n=3	9.73 ± 17.234
Body weight, Visit 32 (Month 120), n=1	0.50 ± 99999
Body weight, Follow up, n=267	1.34 ± 5.870

Notes
[14] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in Electocardiogram (ECG) parameters PR, QRS, QT, corrected QT interval (QTc) Bazett and QTc Friedericia

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End point title

Change from Baseline in Electocardiogram (ECG) parameters PR, QRS, QT, corrected QT interval (QTc) Bazett and QTc Friedericia ^[15]

End point description

A 12-lead ECG was performed at all study visits during the Open-Label Treatment Phase during the first year of the open-label extension study (Months 1, 3, 6, 9, 12) and at the end of each 12 month study cycle that the participant was enrolled (i.e., second year, third year, fourth year, etc.). The ECG parameters that were assessed were PR interval, QRS interval, QRS duration, QT interval, and QTc interval. QT intervals were corrected using both Bazett’s and Friedericia’s formulas. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates data was not available. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[16]
Units: Milliseconds
arithmetic mean (standard deviation)
PR interval, Visit 1 (Month 1), n=355	0.1 ± 13.47
PR interval, Visit 2 (Month 3), n=324	-0.4 ± 11.95
PR interval, Visit 3 (Month 6), n=278	-1.0 ± 13.18
PR interval, Visit 4 (Month 9), n=245	-1.7 ± 12.74
PR interval, Visit 5 (Month 12), n=233	-1.7 ± 13.01
PR interval, Visit 8 (Month 24), n=158	-2.1 ± 15.23
PR interval, Visit 11 (Month 36), n=113	-1.6 ± 14.20
PR interval, Visit 14 (Month 48), n=98	0.3 ± 13.30
PR interval, Visit 17 (Month 60), n=87	0.7 ± 13.70
PR interval, Visit 20 (Month 72), n=52	0.9 ± 14.07
PR interval, Visit 23 (Month 84), n=30	-3.5 ± 13.06
PR interval, Visit 26 (Month 96), n=22	-4.4 ± 11.96
PR interval, Visit 29 (Month 108), n=13	-1.9 ± 11.50
PR interval, Visit 32 (Month 120), n=1	-23.7 ± 99999
PR interval, Follow up, n=252	-1.3 ± 12.83
QRS duration, Visit 1 (Month 1), n=357	-0.6 ± 8.03
QRS duration, Visit 2 (Month 3), n=327	-1.1 ± 7.53
QRS duration, Visit 3 (Month 6), n=282	-1.2 ± 7.34
QRS duration, Visit 4 (Month 9), n=249	-1.4 ± 6.59
QRS duration, Visit 5 (Month 12), n=235	-0.1 ± 8.09
QRS duration, Visit 8 (Month 24), n=160	-1.1 ± 7.74
QRS duration, Visit 11 (Month 36), n=116	1.5 ± 7.66
QRS duration, Visit 14 (Month 48), n=99	1.1 ± 7.92
QRS duration, Visit 17 (Month 60), n=89	3.3 ± 12.89
QRS duration, Visit 20 (Month 72), n=56	5.2 ± 16.42
QRS duration, Visit 23 (Month 84), n=32	3.4 ± 18.65
QRS duration Visit 26 (Month 96), n=23	3.5 ± 24.77
QRS duration, Visit 29 (Month 108), n=13	1.2 ± 7.73
QRS duration, Visit 32 (Month 120), n=1	10.7 ± 99999
QRS duration, Follow up, n=254	-0.1 ± 8.74
QT interval, Visit 1 (Month 1), n=357	5.5 ± 23.66
QT interval, Visit 2 (Month 3), n=324	4.8 ± 23.35
QT interval, Visit 3 (Month 6), n=278	5.3 ± 23.10
QT interval, Visit 4 (Month 9), n=246	3.9 ± 23.47
QT interval, Visit 5 (Month 12), n=232	5.0 ± 24.37
QT interval, Visit 8 (Month 24), n=157	3.4 ± 25.09
QT interval, Visit 11 (Month 36), n=112	8.8 ± 24.66
QT interval, Visit 14 (Month 48), n=96	7.0 ± 22.57
QT interval, Visit 17 (Month 60), n=89	7.9 ± 23.55
QT interval, Visit 20 (Month 72), n=56	12.4 ± 28.30
QT interval, Visit 23 (Month 84), n=32	8.4 ± 30.17
QT interval, Visit 26 (Month 96), n=23	4.0 ± 31.01
QT interval, Visit 29 (Month 108), n=13	0.8 ± 29.90
QT interval, Visit 32 (Month 120), n=1	64.0 ± 99999
QT interval, Follow up, n=254	1.2 ± 24.95
QTc Bazett interval, Visit 1 (Month 1, n=357	1.2 ± 18.07
QTc Bazett interval, Visit 2 (Month 3), n=324	1.6 ± 18.09
QTc Bazett interval, Visit 3 (Month 6), n=278	3.4 ± 16.97
QTc Bazett interval, Visit 4 (Month 9, n=246	4.4 ± 17.33
QTc Bazett interval, Visit 5 (Month 12), n=232	2.3 ± 16.61
QTc Bazett interval, Visit 8 (Month 24), n=157	6.6 ± 18.27
QTc Bazett interval, Visit 11 (Month 36), n=112	4.5 ± 18.10
QTc Bazett interval, Visit 14 (Month 48), n=96	5.6 ± 18.18
QTc Bazett interval, Visit 17 (Month 60), n=89	12.4 ± 25.68
QTc Bazett interval, Visit 20 (Month 72), n=56	15.6 ± 24.79
QTc Bazett interval, Visit 23 (Month 84), n=32	18.7 ± 23.90
QTc Bazett interval, Visit 26 (Month 96, n=23	19.7 ± 28.67
QTc Bazett interval, Visit 29 (Month 108), n=13	17.6 ± 21.09
QTc Bazett interval, Visit 32 (Month 120), n=1	0.7 ± 99999
QTc Bazett interval, Follow up, n=254	4.9 ± 18.39
QTc Friedericia interval, Visit 1 (Month 1),n=357	2.7 ± 15.72
QTc Friedericia interval Visit 2 (Month 3),n=324	2.7 ± 15.88
QTc Friedericia interval,Visit 3 (Month 6),n=278	4.0 ± 15.59
QTc Friedericia interval, Visit 4 (Month 9),n=246	4.1 ± 15.86
QTc Friedericia intervalVisit 5 (Month 12),n=232	3.2 ± 15.62
QTc Friedericia interval,Visit 8 (Month 24),n=157	5.4 ± 15.00
QTc Friedericia intervalVisit 11 (Month 36),n=112	5.9 ± 15.69
QTc Friedericia interval,Visit 14 (Month 48),n=96	6.1 ± 15.08
QTc Friedericia interval,Visit 17 (Month 60),n=89	10.8 ± 18.93
QTc Friedericia intervalVisit 20 (Month 72),n=56	14.4 ± 19.28
QTc Friedericia intervalVisit 23 (Month 84),n=32	15.0 ± 20.97
QTc Friedericia interval,Visit 26 (Month 96),n=23	14.3 ± 22.90
QTcFriedericia intervalVisit 29 (Month 108)n=13	11.6 ± 17.76
QTc Friedericia interval,Visit 32 (Month 120),n=1	23.7 ± 99999
QTcFriedericia interval, Follow up,n=254	3.5 ± 16.58

Notes
[16] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in alkaline phosphatase (Alk. Phos.), alanine amino transferase (ALT) and aspartate amino transferase (AST)

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End point title

Change from Baseline in alkaline phosphatase (Alk. Phos.), alanine amino transferase (ALT) and aspartate amino transferase (AST) ^[17]

End point description

Clinical chemistry parameters included Alk. Phos., ALT and AST. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[18]
Units: International units per liter
arithmetic mean (standard deviation)
Alk. Phos., Visit 1 (Month 1), n=352	-0.9 ± 14.47
Alk. Phos., Visit 1a (Month 2), n=1	-18.0 ± 99999
Alk. Phos., Visit 2 (Month 3), n=322	-1.5 ± 14.56
Alk. Phos., Visit 2a (Month 4), n=1	4.0 ± 99999
Alk. Phos., Visit 3 (Month 6), n=279	-1.2 ± 14.91
Alk. Phos., Visit 4 (Month 9), n=248	-3.0 ± 14.25
Alk. Phos., Visit 5 (Month 12), n=228	-1.9 ± 15.06
Alk. Phos., Visit 6 (Month 16), n=200	-1.8 ± 15.96
Alk. Phos., Visit 7 (Month 20), n=176	-3.6 ± 17.32
Alk. Phos., Visit 8 (Month 24), n=163	-4.0 ± 17.68
Alk. Phos., Visit 9 (Month 28), n=142	-3.1 ± 17.88
Alk. Phos., Visit 10 (Month 32), n=126	-4.6 ± 18.94
Alk. Phos., Visit 11 (Month 36), n=116	-6.2 ± 22.36
Alk. Phos., Visit 12 (Month 40), n=108	-4.8 ± 21.05
Alk. Phos., Visit 13 (Month 44), n=101	-5.8 ± 21.53
Alk. Phos., Visit 14 (Month 48), n=101	-7.2 ± 21.34
Alk. Phos., Visit 15 (Month 52), n=88	-2.5 ± 23.46
Alk. Phos., Visit 16 (Month 56), n=76	-0.1 ± 19.72
Alk. Phos., Visit 17 (Month 60), n=90	-5.1 ± 21.15
Alk. Phos., Visit 18 (Month 64), n=55	-2.0 ± 18.95
Alk. Phos., Visit 19 (Month 68), n=50	-0.6 ± 14.60
Alk. Phos., Visit 20 (Month 72), n=58	0.3 ± 23.56
Alk. Phos., Visit 21 (Month 76), n=40	0.8 ± 15.41
Alk. Phos., Visit 22 (Month 80), n=35	3.2 ± 19.97
Alk. Phos., Visit 23 (Month 84), n=32	0.2 ± 16.54
Alk. Phos., Visit 24 (Month 88), n=28	-0.1 ± 19.55
Alk. Phos., Visit 25 (Month 92), n=25	1.5 ± 21.27
Alk. Phos., Visit 26 (Month 96), n=26	4.8 ± 23.10
Alk. Phos., Visit 27 (Month 100), n=20	4.1 ± 14.67
Alk. Phos., Visit 28 (Month 104), n=16	8.6 ± 21.80
Alk. Phos., Visit 29 (Month 108), n=13	6.6 ± 17.94
Alk. Phos., Visit 30 (Month 112), n=4	1.8 ± 14.57
Alk. Phos., Visit 31 (Month 116), n=3	3.0 ± 3.61
Alk. Phos., Visit 32 (Month 120), n=1	1.0 ± 99999
Alk. Phos., Follow up, n=261	-0.4 ± 18.15
ALT, Visit 1 (Month 1), n=352	2.6 ± 20.05
ALT, Visit 1a (Month 2), n=1	-24.0 ± 99999
ALT, Visit 2 (Month 3), n=322	1.5 ± 16.57
ALT, Visit 2a (Month 4), n=1	45.0 ± 99999
ALT, Visit 3 (Month 6), n=278	1.3 ± 13.99
ALT, Visit 4 (Month 9), n=246	-0.2 ± 10.94
ALT, Visit 5 (Month 12), n=227	3.4 ± 28.91
ALT, Visit 6 (Month 16), n=200	1.3 ± 12.56
ALT, Visit 7 (Month 20), n=174	1.2 ± 17.23
ALT, Visit 8 (Month 24), n=163	0.5 ± 11.03
ALT, Visit 9 (Month 28), n=141	1.7 ± 16.40
ALT, Visit 10 (Month 32), n=126	1.0 ± 9.95
ALT, Visit 11 (Month 36), n=115	0.1 ± 8.11
ALT, Visit 12 (Month 40), n=107	0.9 ± 8.49
ALT, Visit 13 (Month 44), n=101	0.6 ± 8.39
ALT, Visit 14 (Month 48), n=99	0.5 ± 8.47
ALT, Visit 15 (Month 52), n=88	0.9 ± 9.83
ALT, Visit 16 (Month 56), n=75	1.3 ± 9.16
ALT, Visit 17 (Month 60), n=89	0.0 ± 8.06
ALT, Visit 18 (Month 64), n=54	-0.8 ± 7.12
ALT, Visit 19 (Month 68), n=50	-0.5 ± 7.57
ALT, Visit 20 (Month 72), n=58	0.6 ± 10.70
ALT, Visit 21 (Month 76), n=39	0.3 ± 10.65
ALT, Visit 22 (Month 80), n=35	0.1 ± 16.27
ALT, Visit 23 (Month 84), n=32	-2.3 ± 7.95
ALT, Visit 24 (Month 88), n=28	-4.1 ± 9.45
ALT, Visit 25 (Month 92), n=25	-4.2 ± 9.99
ALT, Visit 26 (Month 96), n=26	-1.6 ± 11.74
ALT, Visit 27 (Month 100), n=20	-3.2 ± 6.76
ALT, Visit 28 (Month 104), n=16	-3.1 ± 12.15
ALT, Visit 29 (Month 108), n=13	-3.6 ± 8.65
ALT, Visit 30 (Month 112), n=4	-5.3 ± 11.84
ALT, Visit 31 (Month 116), n=3	2.3 ± 18.15
ALT, Visit 32 (Month 120), n=1	1.0 ± 99999
ALT, Follow up, n=259	5.5 ± 64.04
AST, Visit 1 (Month 1), n=352	2.1 ± 13.00
AST, Visit 1a (Month 2), n=1	-65.0 ± 99999
AST, Visit 2 (Month 3), n=322	1.8 ± 14.76
AST, Visit 2a (Month 4), n=1	24.0 ± 99999
AST, Visit 3 (Month 6), n=278	1.0 ± 9.60
AST, Visit 4 (Month 9), n=246	0.7 ± 8.90
AST, Visit 5 (Month 12), n=227	3.0 ± 16.88
AST, Visit 6 (Month 16), n=200	1.7 ± 7.95
AST, Visit 7 (Month 20), n=174	2.7 ± 10.53
AST, Visit 8 (Month 24), n=162	2.7 ± 8.42
AST, Visit 9 (Month 28), n=141	3.3 ± 11.36
AST, Visit 10 (Month 32), n=126	3.3 ± 7.36
AST, Visit 11 (Month 36), n=115	3.2 ± 7.77
AST, Visit 12 (Month 40), n=106	3.6 ± 8.78
AST, Visit 13 (Month 44), n=101	3.7 ± 8.37
AST, Visit 14 (Month 48), n=99	3.9 ± 7.67
AST, Visit 15 (Month 52), n=87	2.7 ± 8.15
AST, Visit 16 (Month 56), n=74	3.7 ± 8.77
AST, Visit 17 (Month 60), n=89	3.6 ± 6.57
AST, Visit 18 (Month 64), n=54	2.1 ± 8.24
AST, Visit 19 (Month 68), n=50	2.3 ± 7.22
AST, Visit 20 (Month 72), n=58	4.0 ± 10.35
AST, Visit 21 (Month 76), n=39	3.9 ± 10.22
AST, Visit 22 (Month 80), n=35	3.8 ± 11.96
AST, Visit 23 (Month 84), n=32	1.9 ± 9.96
AST, Visit 24 (Month 88), n=28	3.5 ± 11.21
AST, Visit 25 (Month 92), n=25	1.3 ± 9.09
AST, Visit 26 (Month 96), n=26	2.5 ± 9.78
AST, Visit 27 (Month 100), n=20	1.6 ± 7.67
AST, Visit 28 (Month 104), n=16	3.2 ± 10.71
AST, Visit 29 (Month 108), n=13	0.7 ± 8.70
AST, Visit 30 (Month 112), n=4	-4.5 ± 10.60
AST, Visit 31 (Month 116), n=3	2.7 ± 23.03
AST, Visit 32 (Month 120), n=1	7.0 ± 99999
AST, Follow up, n=257	3.4 ± 36.36

Notes
[18] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in bicarbonate, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium and urea

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End point title

Change from Baseline in bicarbonate, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium and urea ^[19]

End point description

Clinical chemistry parameters included bicarbonate, calcium, chloride, cholesterol, Non-fasting Glucose, phosphorus, potassium, sodium and urea. Approximately 7-milliliter sample of blood was drawn for clinical chemistry assays. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[20]
Units: Millimoles per liter
arithmetic mean (standard deviation)
Bicarbonate, Visit 1 (Month 1), n=344	-0.2 ± 3.02
Bicarbonate, Visit 1a (Month 2), n=1	-2.0 ± 99999
Bicarbonate, Visit 2 (Month 3), n=316	-0.3 ± 3.34
Bicarbonate, Visit 3 (Month 6), n=272	0.0 ± 3.06
Bicarbonate, Visit 4 (Month 9), n=243	-0.3 ± 3.22
Bicarbonate, Visit 5 (Month 12), n=221	-0.8 ± 3.18
Bicarbonate, Visit 6 (Month 16), n=196	-0.2 ± 3.11
Bicarbonate, Visit 7 (Month 20), n=171	-0.2 ± 3.22
Bicarbonate, Visit 8 (Month 24), n=159	-0.2 ± 3.26
Bicarbonate, Visit 9 (Month 28), n=140	-0.1 ± 3.44
Bicarbonate, Visit 10 (Month 32), n=126	-0.5 ± 3.74
Bicarbonate, Visit 11 (Month 36), n=116	-0.4 ± 3.54
Bicarbonate, Visit 12 (Month 40), n=107	0.0 ± 3.52
Bicarbonate, Visit 13 (Month 44), n=100	0.4 ± 3.41
Bicarbonate, Visit 14 (Month 48), n=101	-0.1 ± 3.56
Bicarbonate, Visit 15 (Month 52), n=86	0.5 ± 3.77
Bicarbonate, Visit 16 (Month 56), n=76	-0.1 ± 3.07
Bicarbonate, Visit 17 (Month 60), n=90	-0.1 ± 3.45
Bicarbonate, Visit 18 (Month 64), n=55	-0.7 ± 3.93
Bicarbonate, Visit 19 (Month 68), n=49	-1.1 ± 4.11
Bicarbonate, Visit 20 (Month 72), n=56	-1.2 ± 3.81
Bicarbonate, Visit 21 (Month 76), n=39	-0.2 ± 3.58
Bicarbonate, Visit 22 (Month 80), n=35	-1.0 ± 3.24
Bicarbonate, Visit 23 (Month 84), n=32	-1.3 ± 3.17
Bicarbonate, Visit 24 (Month 88), n=28	-0.7 ± 3.56
Bicarbonate, Visit 25 (Month 92), n=25	-1.8 ± 3.15
Bicarbonate, Visit 26 (Month 96), n=25	-1.0 ± 3.48
Bicarbonate, Visit 27 (Month 100), n=20	-1.3 ± 3.91
Bicarbonate, Visit 28 (Month 104), n=15	-1.9 ± 3.70
Bicarbonate, Visit 29 (Month 108), n=13	-1.8 ± 2.35
Bicarbonate, Visit 30 (Month 112), n=4	-2.0 ± 1.41
Bicarbonate, Visit 31 (Month 116), n=3	3.3 ± 6.11
Bicarbonate, Visit 32 (Month 120), n=1	2.0 ± 99999
Bicarbonate, Follow up, n=256	-1.0 ± 3.19
Calcium, Visit 1 (Month 1), n=352	0.000 ± 0.1187
Calcium, Visit 1a (Month 2), n=1	-0.250 ± 99999
Calcium, Visit 2 (Month 3), n=322	0.008 ± 0.1146
Calcium, Visit 2a (Month 4), n=1	-0.100 ± 99999
Calcium, Visit 3 (Month 6), n=279	0.018 ± 0.1169
Calcium, Visit 4 (Month 9), n=248	0.022 ± 0.1187
Calcium, Visit 5 (Month 12), n=228	0.010 ± 0.1269
Calcium, Visit 6 (Month 16), n=200	0.005 ± 0.1168
Calcium, Visit 7 (Month 20), n=176	0.005 ± 0.1118
Calcium, Visit 8 (Month 24), n=163	0.014 ± 0.1193
Calcium, Visit 9 (Month 28), n=142	0.015 ± 0.1154
Calcium, Visit 10 (Month 32), n=126	0.023 ± 0.1161
Calcium, Visit 11 (Month 36), n=116	0.017 ± 0.1274
Calcium, Visit 12 (Month 40), n=108	0.035 ± 0.1239
Calcium, Visit 13 (Month 44), n=101	0.028 ± 0.1168
Calcium, Visit 14 (Month 48), n=101	0.025 ± 0.1176
Calcium, Visit 15 (Month 52), n=88	0.020 ± 0.1225
Calcium, Visit 16 (Month 56), n=76	0.016 ± 0.1227
Calcium, Visit 17 (Month 60), n=90	0.008 ± 0.1172
Calcium, Visit 18 (Month 64), n=55	-0.007 ± 0.1270
Calcium, Visit 19 (Month 68), n=51	0.019 ± 0.1177
Calcium, Visit 20 (Month 72), n=58	-0.012 ± 0.1298
Calcium, Visit 21 (Month 76), n=40	0.020 ± 0.1257
Calcium, Visit 22 (Month 80), n=35	0.079 ± 0.1531
Calcium, Visit 23 (Month 84), n=32	0.038 ± 0.1113
Calcium, Visit 24 (Month 88), n=28	0.034 ± 0.1497
Calcium, Visit 25 (Month 92), n=25	0.089 ± 0.1560
Calcium, Visit 26 (Month 96), n=26	0.075 ± 0.1636
Calcium, Visit 27 (Month 100), n=20	0.121 ± 0.1552
Calcium, Visit 28 (Month 104), n=16	0.091 ± 0.1653
Calcium, Visit 29 (Month 108), n=13	0.080 ± 0.1297
Calcium, Visit 30 (Month 112), n=4	0.133 ± 0.1063
Calcium, Visit 31 (Month 116), n=3	0.053 ± 0.1124
Calcium, Visit 32 (Month 120), n=1	-0.040 ± 99999
Calcium, Follow up, n=261	0.031 ± 0.1245
Chloride, Visit 1 (Month 1), n=352	0.1 ± 3.48
Chloride, Visit 1a (Month 2), n=1	1.0 ± 99999
Chloride, Visit 2 (Month 3), n=322	0.3 ± 3.49
Chloride, Visit 2a (Month 4), n=1	2.0 ± 99999
Chloride, Visit 3 (Month 6), n=279	0.9 ± 3.52
Chloride, Visit 4 (Month 9), n=248	1.0 ± 3.46
Chloride, Visit 5 (Month 12), n=228	1.2 ± 3.75
Chloride, Visit 6 (Month 16), n=200	1.8 ± 3.73
Chloride, Visit 7 (Month 20), n=176	2.0 ± 4.09
Chloride, Visit 8 (Month 24), n=164	1.8 ± 4.42
Chloride, Visit 9 (Month 28), n=143	2.1 ± 4.45
Chloride, Visit 10 (Month 32), n=127	1.3 ± 4.22
Chloride, Visit 11 (Month 36), n=118	1.3 ± 4.55
Chloride, Visit 12 (Month 40), n=108	2.4 ± 4.68
Chloride, Visit 13 (Month 44), n=103	2.2 ± 4.59
Chloride, Visit 14 (Month 48), n=102	1.2 ± 4.91
Chloride, Visit 15 (Month 52), n=89	2.0 ± 4.63
Chloride, Visit 16 (Month 56), n=76	1.6 ± 4.51
Chloride, Visit 17 (Month 60), n=91	1.3 ± 5.16
Chloride, Visit 18 (Month 64), n=55	2.3 ± 3.33
Chloride, Visit 19 (Month 68), n=51	0.9 ± 4.22
Chloride, Visit 20 (Month 72), n=58	0.2 ± 5.33
Chloride, Visit 21 (Month 76), n=40	0.6 ± 4.11
Chloride, Visit 22 (Month 80), n=35	0.8 ± 3.30
Chloride, Visit 23 (Month 84), n=32	1.1 ± 4.33
Chloride, Visit 24 (Month 88), n=28	0.8 ± 3.94
Chloride, Visit 25 (Month 92), n=25	-0.4 ± 5.97
Chloride, Visit 26 (Month 96), n=26	-0.4 ± 4.56
Chloride, Visit 27 (Month 100), n=20	0.1 ± 5.31
Chloride, Visit 28 (Month 104), n=16	-1.1 ± 4.86
Chloride, Visit 29 (Month 108), n=13	-1.0 ± 5.66
Chloride,Visit 30 (Month 112), n=4	-3.0 ± 4.24
Chloride,Visit 31 (Month 116), n=3	-2.3 ± 5.03
Chloride, Visit 32 (Month 120), n=1	-3.0 ± 99999
Chloride, Follow up, n=261	0.3 ± 4.03
Cholesterol, Visit 1 (Month 1), n=352	0.066 ± 0.6255
Cholesterol, Visit 1a (Month 2), n=1	-0.360 ± 99999
Cholesterol, Visit 2 (Month 3), n=322	0.108 ± 0.6368
Cholesterol, Visit 2a (Month 4), n=1	-0.470 ± 99999
Cholesterol, Visit 3 (Month 6), n=279	0.062 ± 0.6978
Cholesterol, Visit 4 (Month 9), n=248	0.062 ± 0.7238
Cholesterol, Visit 5 (Month 12), n=228	0.075 ± 0.7074
Cholesterol, Visit 6 (Month 16), n=200	0.101 ± 0.7601
Cholesterol, Visit 7 (Month 20), n=176	0.001 ± 0.7820
Cholesterol, Visit 8 (Month 24), n=163	0.087 ± 0.8471
Cholesterol, Visit 9 (Month 28), n=142	-0.001 ± 0.7732
Cholesterol, Visit 10 (Month 32), n=126	-0.028 ± 0.8520
Cholesterol, Visit 11 (Month 36), n=116	-0.087 ± 0.7823
Cholesterol, Visit 12 (Month 40), n=108	-0.001 ± 0.7830
Cholesterol, Visit 13 (Month 44), n=101	-0.043 ± 0.8053
Cholesterol, Visit 14 (Month 48), n=101	-0.128 ± 0.7505
Cholesterol, Visit 15 (Month 52), n=88	-0.057 ± 0.7427
Cholesterol, Visit 16 (Month 56), n=76	0.026 ± 0.7354
Cholesterol, Visit 17 (Month 60), n=90	0.016 ± 0.8209
Cholesterol, Visit 18 (Month 64), n=55	0.054 ± 0.7474
Cholesterol, Visit 19 (Month 68), n=50	0.074 ± 0.8943
Cholesterol, Visit 20 (Month 72), n=58	-0.048 ± 0.8221
Cholesterol, Visit 21 (Month 76), n=40	0.103 ± 0.9056
Cholesterol, Visit 22 (Month 80), n=35	0.096 ± 0.8671
Cholesterol, Visit 23 (Month 84), n=32	0.077 ± 0.9637
Cholesterol, Visit 24 (Month 88), n=28	0.310 ± 0.8553
Cholesterol, Visit 25 (Month 92), n=25	0.327 ± 0.8143
Cholesterol, Visit 26 (Month 96), n=26	0.489 ± 1.0353
Cholesterol, Visit 27 (Month 100), n=20	0.370 ± 0.6675
Cholesterol, Visit 28 (Month 104), n=16	0.354 ± 0.6488
Cholesterol, Visit 29 (Month 108), n=13	0.141 ± 1.0346
Cholesterol, Visit 30 (Month 112), n=4	1.775 ± 0.9858
Cholesterol, Visit 31 (Month 116), n=3	1.123 ± 0.8723
Cholesterol, Visit 32 (Month 120), n=1	0.050 ± 99999
Cholesterol, Follow up, n=261	-0.070 ± 0.7047
Non-fasting Glucose, Visit 1 (Month 1), n=351	0.06 ± 0.885
Non-fasting Glucose, Visit 1a (Month 2), n=1	-0.30 ± 99999
Non-fasting Glucose, Visit 2 (Month 3), n=321	0.17 ± 1.002
Non-fasting Glucose, Visit 2a (Month 4), n=1	0.40 ± 99999
Non-fasting Glucose, Visit 3 (Month 6), n=278	0.12 ± 0.804
Non-fasting Glucose, Visit 4 (Month 9), n=247	0.16 ± 1.066
Non-fasting Glucose, Visit 5 (Month 12), n=227	0.16 ± 0.906
Non-fasting Glucose, Visit 6 (Month 16), n=199	0.10 ± 0.851
Non-fasting Glucose, Visit 7 (Month 20), n=176	0.02 ± 0.843
Non-fasting Glucose, Visit 8 (Month 24), n=161	0.12 ± 0.858
Non-fasting Glucose, Visit 9 (Month 28), n=142	0.04 ± 0.842
Non-fasting Glucose, Visit 10 (Month 32), n=126	0.03 ± 0.976
Non-fasting Glucose, Visit 11 (Month 36), n=115	0.08 ± 0.951
Non-fasting Glucose, Visit 12 (Month 40), n=108	0.06 ± 0.938
Non-fasting Glucose, Visit 13 (Month 44), n=100	0.07 ± 0.912
Non-fasting Glucose, Visit 14 (Month 48), n=101	-0.04 ± 0.881
Non-fasting Glucose, Visit 15 (Month 52), n=88	0.08 ± 0.745
Non-fasting Glucose, Visit 16 (Month 56), n=75	0.19 ± 0.931
Non-fasting Glucose, Visit 17 (Month 60), n=89	0.08 ± 0.773
Non-fasting Glucose, Visit 18 (Month 64), n=55	0.14 ± 1.125
Non-fasting Glucose, Visit 19 (Month 68), n=49	0.05 ± 0.816
Non-fasting Glucose, Visit 20 (Month 72), n=58	0.16 ± 0.878
Non-fasting Glucose, Visit 21 (Month 76), n=40	0.03 ± 0.895
Non-fasting Glucose, Visit 22 (Month 80), n=35	0.29 ± 1.116
Non-fasting Glucose, Visit 23 (Month 84), n=32	-0.01 ± 0.903
Non-fasting Glucose, Visit 24 (Month 88), n=28	0.14 ± 1.017
Non-fasting Glucose, Visit 25 (Month 92), n=25	0.28 ± 1.105
Non-fasting Glucose, Visit 26 (Month 96), n=26	0.50 ± 1.381
Non-fasting Glucose, Visit 27 (Month 100), n=20	0.18 ± 1.022
Non-fasting Glucose, Visit 28 (Month 104), n=16	0.74 ± 0.916
Non-fasting Glucose, Visit 29 (Month 108), n=13	0.25 ± 0.989
Non-fasting Glucose, Visit 30 (Month 112), n=4	0.65 ± 0.839
Non-fasting Glucose, Visit 31 (Month 116), n=3	0.70 ± 1.127
Non-fasting Glucose, Visit 32 (Month 120), n=1	-0.30 ± 99999
Non-fasting Glucose, Follow up, n=259	0.18 ± 1.068
Phosphorus, Visit 1 (Month 1), n=351	0.017 ± 0.1991
Phosphorus, Visit 1a (Month 2), n=1	0.030 ± 99999
Phosphorus, Visit 2 (Month 3), n=320	0.014 ± 0.2011
Phosphorus, Visit 2a (Month 4), n=1	0.160 ± 99999
Phosphorus, Visit 3 (Month 6), n=278	-0.001 ± 0.2125
Phosphorus, Visit 4 (Month 9), n=247	-0.009 ± 0.1912
Phosphorus, Visit 5 (Month 12), n=227	-0.016 ± 0.2130
Phosphorus, Visit 6 (Month 16), n=199	-0.023 ± 0.1994
Phosphorus, Visit 7 (Month 20), n=176	-0.022 ± 0.2224
Phosphorus, Visit 8 (Month 24), n=161	-0.012 ± 0.2332
Phosphorus, Visit 9 (Month 28), n=142	-0.011 ± 0.2146
Phosphorus, Visit 10 (Month 32), n=126	-0.005 ± 0.2231
Phosphorus, Visit 11 (Month 36), n=115	-0.026 ± 0.2284
Phosphorus, Visit 12 (Month 40), n=108	-0.030 ± 0.2585
Phosphorus, Visit 13 (Month 44), n=100	-0.026 ± 0.2241
Phosphorus, Visit 14 (Month 48), n=101	-0.050 ± 0.2331
Phosphorus, Visit 15 (Month 52), n=88	-0.054 ± 0.2207
Phosphorus, Visit 16 (Month 56), n=75	-0.052 ± 0.2465
Phosphorus, Visit 17 (Month 60), n=89	-0.047 ± 0.2419
Phosphorus, Visit 18 (Month 64), n=55	-0.059 ± 0.2540
Phosphorus, Visit 19 (Month 68), n=49	-0.047 ± 0.2905
Phosphorus, Visit 20 (Month 72), n=58	-0.076 ± 0.2502
Phosphorus, Visit 21 (Month 76), n=40	-0.074 ± 0.2503
Phosphorus, Visit 22 (Month 80), n=35	-0.071 ± 0.2930
Phosphorus, Visit 23 (Month 84), n=32	-0.068 ± 0.3006
Phosphorus, Visit 24 (Month 88), n=28	-0.115 ± 0.3460
Phosphorus, Visit 25 (Month 92), n=25	-0.130 ± 0.3251
Phosphorus, Visit 26 (Month 96), n=26	-0.098 ± 0.2820
Phosphorus, Visit 27 (Month 100), n=20	-0.197 ± 0.3030
Phosphorus, Visit 28 (Month 104), n=16	-0.261 ± 0.2665
Phosphorus, Visit 29 (Month 108), n=13	-0.300 ± 0.1534
Phosphorus, Visit 30 (Month 112), n=4	-0.065 ± 0.0603
Phosphorus, Visit 31 (Month 116), n=3	-0.260 ± 0.0000
Phosphorus, Visit 32 (Month 120), n=1	-0.320 ± 99999
Phosphorus, Follow up, n=260	-0.038 ± 0.2237
Potassium, Visit 1 (Month 1), n=351	-0.02 ± 0.426
Potassium, Visit 1a (Month 2), n=1	-0.40 ± 99999
Potassium, Visit 2 (Month 3), n=322	-0.05 ± 0.410
Potassium, Visit 2a (Month 4), n=1	0.40 ± 99999
Potassium, Visit 3 (Month 6), n=279	-0.04 ± 0.424
Potassium, Visit 4 (Month 9), n=247	-0.08 ± 0.427
Potassium, Visit 5 (Month 12), n=230	-0.07 ± 0.440
Potassium, Visit 6 (Month 16), n=199	0.00 ± 0.436
Potassium, Visit 7 (Month 20), n=174	-0.02 ± 0.434
Potassium, Visit 8 (Month 24), n=162	-0.03 ± 0.430
Potassium, Visit 9 (Month 28), n=143	-0.01 ± 0.434
Potassium, Visit 10 (Month 32), n=127	-0.01 ± 0.451
Potassium, Visit 11 (Month 36), n=116	-0.01 ± 0.457
Potassium, Visit 12 (Month 40), n=108	-0.05 ± 0.475
Potassium, Visit 13 (Month 44), n=102	-0.06 ± 0.466
Potassium, Visit 14 (Month 48), n=101	-0.01 ± 0.443
Potassium, Visit 15 (Month 52), n=89	-0.01 ± 0.436
Potassium, Visit 16 (Month 56), n=75	0.00 ± 0.506
Potassium, Visit 17 (Month 60), n=89	-0.05 ± 0.477
Potassium, Visit 18 (Month 64), n=55	-0.12 ± 0.468
Potassium, Visit 19 (Month 68), n=50	-0.03 ± 0.484
Potassium, Visit 20 (Month 72), n=58	-0.10 ± 0.485
Potassium, Visit 21 (Month 76), n=39	-0.11 ± 0.469
Potassium, Visit 22 (Month 80), n=35	-0.08 ± 0.461
Potassium, Visit 23 (Month 84), n=32	0.01 ± 0.523
Potassium, Visit 24 (Month 88), n=28	-0.05 ± 0.517
Potassium, Visit 25 (Month 92), n=25	-0.01 ± 0.488
Potassium, Visit 26 (Month 96), n=26	-0.02 ± 0.603
Potassium, Visit 27 (Month 100), n=20	-0.09 ± 0.609
Potassium, Visit 28 (Month 104), n=16	-0.18 ± 0.481
Potassium, Visit 29 (Month 108), n=13	-0.09 ± 0.647
Potassium, Visit 30 (Month 112), n=4	-0.38 ± 0.574
Potassium, Visit 31 (Month 116), n=3	-0.83 ± 0.611
Potassium, Visit 32 (Month 120), n=1	-0.30 ± 99999
Potassium, Follow up, n=258	-0.02 ± 0.456
Sodium, Visit 1 (Month 1), n=352	-0.3 ± 3.60
Sodium, Visit 1a (Month 2), n=1	0.0 ± 99999
Sodium, Visit 2 (Month 3), n=324	-0.1 ± 3.52
Sodium, Visit 2a (Month 4), n=1	1.0 ± 99999
Sodium, Visit 3 (Month 6), n=280	0.8 ± 3.49
Sodium, Visit 4 (Month 9), n=248	0.5 ± 3.50
Sodium, Visit 5 (Month 12), n=231	0.6 ± 3.84
Sodium, Visit 6 (Month 16), n=200	0.9 ± 3.81
Sodium, Visit 7 (Month 20), n=176	1.1 ± 3.88
Sodium, Visit 8 (Month 24), n=164	1.0 ± 4.38
Sodium, Visit 9 (Month 28), n=143	1.6 ± 4.36
Sodium, Visit 10 (Month 32), n=127	1.2 ± 4.08
Sodium, Visit 11 (Month 36), n=118	1.3 ± 5.15
Sodium, Visit 12 (Month 40), n=108	1.9 ± 4.25
Sodium, Visit 13 (Month 44), n=103	1.7 ± 4.06
Sodium, Visit 14 (Month 48), n=102	1.1 ± 4.44
Sodium, Visit 15 (Month 52), n=89	1.8 ± 4.29
Sodium, Visit 16 (Month 56), n=76	1.7 ± 3.75
Sodium, Visit 17 (Month 60), n=91	1.8 ± 4.62
Sodium, Visit 18 (Month 64), n=55	2.7 ± 3.32
Sodium, Visit 19 (Month 68), n=51	2.2 ± 3.63
Sodium, Visit 20 (Month 72), n=58	1.0 ± 4.46
Sodium, Visit 21 (Month 76), n=40	2.2 ± 3.82
Sodium, Visit 22 (Month 80), n=35	2.0 ± 3.11
Sodium, Visit 23 (Month 84), n=32	2.4 ± 3.72
Sodium, Visit 24 (Month 88), n=28	1.9 ± 3.85
Sodium, Visit 25 (Month 92), n=25	1.4 ± 5.45
Sodium, Visit 26 (Month 96), n=26	1.8 ± 4.48
Sodium, Visit 27 (Month 100), n=20	1.8 ± 4.76
Sodium, Visit 28 (Month 104), n=16	0.9 ± 3.14
Sodium, Visit 29 (Month 108), n=13	0.5 ± 4.58
Sodium, Visit 30 (Month 112), n=4	-0.3 ± 5.85
Sodium, Visit 31 (Month 116), n=3	0.7 ± 3.79
Sodium, Visit 32 (Month 120), n=1	-5.0 ± 99999
Sodium, Follow up, n=261	0.3 ± 3.91
Urea, Visit 1 (Month 1), n=351	0.583 ± 1.2933
Urea, Visit 1a (Month 2), n=1	2.860 ± 99999
Urea, Visit 2 (Month 3), n=322	0.606 ± 1.2846
Urea, Visit 2a (Month 4), n=1	1.780 ± 99999
Urea, Visit 3 (Month 6), n=279	0.623 ± 1.3294
Urea, Visit 4 (Month 9), n=248	0.642 ± 1.3781
Urea, Visit 5 (Month 12), n=228	0.599 ± 1.3323
Urea, Visit 6 (Month 16), n=200	0.656 ± 1.3598
Urea, Visit 7 (Month 20), n=176	0.750 ± 1.3893
Urea, Visit 8 (Month 24), n=163	0.652 ± 1.5332
Urea, Visit 9 (Month 28), n=142	0.578 ± 1.3512
Urea, Visit 10 (Month 32), n=126	0.748 ± 1.5680
Urea, Visit 11 (Month 36), n=117	0.552 ± 1.6650
Urea, Visit 12 (Month 40), n=108	0.794 ± 1.5456
Urea, Visit 13 (Month 44), n=102	0.697 ± 1.5664
Urea, Visit 14 (Month 48), n=101	0.792 ± 1.7321
Urea, Visit 15 (Month 52), n=88	0.828 ± 1.4226
Urea, Visit 16 (Month 56), n=76	0.742 ± 1.3964
Urea, Visit 17 (Month 60), n=90	0.778 ± 1.5392
Urea, Visit 18 (Month 64), n=55	0.766 ± 1.5980
Urea, Visit 19 (Month 68), n=51	0.791 ± 1.3485
Urea, Visit 20 (Month 72), n=58	0.794 ± 1.5895
Urea, Visit 21 (Month 76), n=40	1.152 ± 1.3824
Urea, Visit 22 (Month 80), n=35	0.939 ± 1.2432
Urea, Visit 23 (Month 84), n=32	0.781 ± 1.3376
Urea, Visit 24 (Month 88), n=28	0.791 ± 1.0485
Urea, Visit 25 (Month 92), n=25	0.529 ± 1.6380
Urea, Visit 26 (Month 96), n=26	0.811 ± 1.4025
Urea, Visit 27 (Month 100), n=20	0.501 ± 1.1668
Urea, Visit 28 (Month 104), n=16	0.536 ± 0.9589
Urea, Visit 29 (Month 108), n=13	0.523 ± 1.2418
Urea, Visit 30 (Month 112), n=4	0.983 ± 1.0297
Urea, Visit 31 (Month 116), n=3	0.837 ± 1.6082
Urea, Visit 32 (Month 120), n=1	-1.070 ± 99999
Urea, Follow up, n=260	0.158 ± 1.2473

Notes
[20] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in creatinine, total bilirubin and uric acid

Top of page

End point title

Change from Baseline in creatinine, total bilirubin and uric acid ^[21]

End point description

Clinical chemistry parameters included creatinine, total bilirubin and uric acid. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[22]
Units: Micromoles per liter
arithmetic mean (standard deviation)
Creatinine, Visit 1 (Month 1), n=351	1.8 ± 12.85
Creatinine, Visit 1a (Month 2), n=1	0.0 ± 99999
Creatinine, Visit 2 (Month 3), n=320	0.9 ± 8.49
Creatinine, Visit 2a (Month 4), n=1	9.0 ± 99999
Creatinine, Visit 3 (Month 6), n=278	0.7 ± 8.89
Creatinine, Visit 4 (Month 9), n=247	0.1 ± 9.04
Creatinine, Visit 5 (Month 12), n=227	0.0 ± 9.33
Creatinine, Visit 6 (Month 16), n=199	0.8 ± 10.14
Creatinine, Visit 7 (Month 20), n=176	0.6 ± 9.84
Creatinine, Visit 8 (Month 24), n=161	0.0 ± 8.81
Creatinine, Visit 9 (Month 28), n=142	-0.2 ± 9.98
Creatinine, Visit 10 (Month 32), n=126	1.3 ± 10.98
Creatinine, Visit 11 (Month 36), n=115	-0.3 ± 10.13
Creatinine, Visit 12 (Month 40), n=108	0.8 ± 10.30
Creatinine, Visit 13 (Month 44), n=101	0.5 ± 10.70
Creatinine, Visit 14 (Month 48), n=101	-0.3 ± 10.49
Creatinine, Visit 15 (Month 52), n=88	0.8 ± 9.55
Creatinine, Visit 16 (Month 56), n=75	1.1 ± 22.92
Creatinine, Visit 17 (Month 60), n=89	-1.6 ± 10.31
Creatinine, Visit 18 (Month 64), n=55	-0.7 ± 11.09
Creatinine, Visit 19 (Month 68), n=50	-0.9 ± 13.22
Creatinine, Visit 20 (Month 72), n=58	-3.6 ± 11.31
Creatinine, Visit 21 (Month 76), n=40	-0.7 ± 13.10
Creatinine, Visit 22 (Month 80), n=35	-2.2 ± 11.98
Creatinine, Visit 23 (Month 84), n=32	-1.4 ± 12.50
Creatinine, Visit 24 (Month 88), n=28	-4.1 ± 12.03
Creatinine, Visit 25 (Month 92), n=25	-3.2 ± 10.84
Creatinine, Visit 26 (Month 96), n=26	-2.6 ± 13.67
Creatinine, Visit 27 (Month 100), n=20	-3.9 ± 11.05
Creatinine, Visit 28 (Month 104), n=16	-4.2 ± 10.63
Creatinine, Visit 29 (Month 108), n=13	-7.7 ± 13.98
Creatinine, Visit 30 (Month 112), n=4	-6.3 ± 6.85
Creatinine, Visit 31 (Month 116), n=3	-18.7 ± 8.50
Creatinine, Visit 32 (Month 120), n=1	-19.0 ± 99999
Creatinine, Follow up, n=260	0.6 ± 9.99
Total Bilirubin, Visit 1 (Month 1), n=351	3.5 ± 3.41
Total Bilirubin, Visit 1a (Month 2), n=1	0.0 ± 99999
Total Bilirubin, Visit 2 (Month 3), n=322	3.5 ± 3.57
Total Bilirubin, Visit 2a (Month 4), n=1	6.0 ± 99999
Total Bilirubin, Visit 3 (Month 6), n=278	3.6 ± 3.62
Total Bilirubin, Visit 4 (Month 9), n=245	3.5 ± 3.63
Total Bilirubin, Visit 5 (Month 12), n=227	3.4 ± 3.56
Total Bilirubin, Visit 6 (Month 16), n=200	3.6 ± 3.69
Total Bilirubin, Visit 7 (Month 20), n=176	3.7 ± 3.60
Total Bilirubin, Visit 8 (Month 24), n=162	3.8 ± 3.70
Total Bilirubin, Visit 9 (Month 28), n=141	3.7 ± 3.57
Total Bilirubin, Visit 10 (Month 32), n=126	4.1 ± 3.68
Total Bilirubin, Visit 11 (Month 36), n=116	4.0 ± 3.82
Total Bilirubin, Visit 12 (Month 40), n=107	3.7 ± 3.44
Total Bilirubin, Visit 13 (Month 44), n=101	3.9 ± 3.46
Total Bilirubin, Visit 14 (Month 48), n=100	3.7 ± 3.67
Total Bilirubin, Visit 15 (Month 52), n=88	3.7 ± 3.37
Total Bilirubin, Visit 16 (Month 56), n=76	3.6 ± 3.47
Total Bilirubin, Visit 17 (Month 60), n=90	3.8 ± 3.36
Total Bilirubin, Visit 18 (Month 64), n=55	3.7 ± 3.68
Total Bilirubin, Visit 19 (Month 68), n=51	3.1 ± 4.12
Total Bilirubin, Visit 20 (Month 72), n=58	3.3 ± 3.69
Total Bilirubin, Visit 21 (Month 76), n=40	3.7 ± 4.02
Total Bilirubin, Visit 22 (Month 80), n=35	3.2 ± 4.22
Total Bilirubin, Visit 23 (Month 84), n=32	3.4 ± 4.01
Total Bilirubin, Visit 24 (Month 88), n=28	3.6 ± 5.04
Total Bilirubin, Visit 25 (Month 92), n=25	5.5 ± 4.57
Total Bilirubin, Visit 26 (Month 96), n=26	5.5 ± 6.59
Total Bilirubin, Visit 27 (Month 100), n=20	5.2 ± 6.29
Total Bilirubin, Visit 28 (Month 104), n=16	5.8 ± 5.01
Total Bilirubin, Visit 29 (Month 108), n=13	5.5 ± 8.32
Total Bilirubin, Visit 30 (Month 112), n=4	5.0 ± 3.65
Total Bilirubin, Visit 31 (Month 116), n=3	2.7 ± 6.03
Total Bilirubin, Visit 32 (Month 120), n=1	11.0 ± 99999
Total Bilirubin, Follow up, n=258	0.0 ± 2.92
Uric acid, Visit 1 (Month 1), n=352	2.1 ± 38.02
Uric acid, Visit 1a (Month 2), n=1	41.0 ± 99999
Uric acid, Visit 2 (Month 3), n=322	5.5 ± 42.30
Uric acid, Visit 2a (Month 4), n=1	107.0 ± 99999
Uric acid, Visit 3 (Month 6), n=279	4.3 ± 44.39
Uric acid, Visit 4 (Month 9), n=248	7.8 ± 41.60
Uric acid, Visit 5 (Month 12), n=228	5.3 ± 45.90
Uric acid, Visit 6 (Month 16), n=200	7.9 ± 49.61
Uric acid, Visit 7 (Month 20), n=176	8.8 ± 50.55
Uric acid, Visit 8 (Month 24), n=163	10.1 ± 54.77
Uric acid, Visit 9 (Month 28), n=142	7.7 ± 59.32
Uric acid, Visit 10 (Month 32), n=126	8.7 ± 55.37
Uric acid, Visit 11 (Month 36), n=116	9.8 ± 55.78
Uric acid, Visit 12 (Month 40), n=108	13.8 ± 64.68
Uric acid, Visit 13 (Month 44), n=101	13.4 ± 61.73
Uric acid, Visit 14 (Month 48), n=101	6.8 ± 61.69
Uric acid, Visit 15 (Month 52), n=88	14.2 ± 69.08
Uric acid, Visit 16 (Month 56), n=76	12.0 ± 60.26
Uric acid, Visit 17 (Month 60), n=90	14.7 ± 61.14
Uric acid, Visit 18 (Month 64), n=55	14.8 ± 58.21
Uric acid, Visit 19 (Month 68), n=50	25.2 ± 62.64
Uric acid, Visit 20 (Month 72), n=58	14.4 ± 62.38
Uric acid, Visit 21 (Month 76), n=40	25.5 ± 67.33
Uric acid, Visit 22 (Month 80), n=35	18.3 ± 63.64
Uric acid, Visit 23 (Month 84), n=32	21.4 ± 60.20
Uric acid, Visit 24 (Month 88), n=28	14.0 ± 72.96
Uric acid, Visit 25 (Month 92), n=25	29.6 ± 79.56
Uric acid, Visit 26 (Month 96), n=26	14.3 ± 69.23
Uric acid, Visit 27 (Month 100), n=20	14.2 ± 71.63
Uric acid, Visit 28 (Month 104), n=16	-1.8 ± 59.67
Uric acid, Visit 29 (Month 108), n=13	9.2 ± 74.02
Uric acid, Visit 30 (Month 112), n=4	46.3 ± 87.78
Uric acid, Visit 31 (Month 116), n=3	-8.0 ± 37.24
Uric acid, Visit 32 (Month 120), n=1	-23.0 ± 99999
Uric acid, Follow up, n=261	11.7 ± 45.09

Notes
[22] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in total protein

Top of page

End point title

Change from Baseline in total protein ^[23]

End point description

Clinical chemistry parameter included total protein. The clinical laboratory evaluation were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[24]
Units: Grams per liter
arithmetic mean (standard deviation)
Total Protein, Visit 1 (Month 1), n=352	-1.1 ± 4.32
Total Protein, Visit 1a (Month 2), n=1	-12.0 ± 99999
Total Protein, Visit 2 (Month 3), n=322	-0.8 ± 4.34
Total Protein, Visit 2a (Month 4), n=1	-3.0 ± 99999
Total Protein, Visit 3 (Month 6), n=279	-1.1 ± 4.18
Total Protein, Visit 4 (Month 9), n=248	-1.8 ± 5.42
Total Protein, Visit 5 (Month 12), n=228	-1.6 ± 4.34
Total Protein, Visit 6 (Month 16), n=200	-1.3 ± 4.24
Total Protein, Visit 7 (Month 20), n=176	-1.8 ± 4.19
Total Protein, Visit 8 (Month 24), n=163	-1.5 ± 4.25
Total Protein, Visit 9 (Month 28), n=142	-1.5 ± 4.22
Total Protein, Visit 10 (Month 32), n=126	-1.3 ± 4.62
Total Protein, Visit 11 (Month 36), n=116	-2.1 ± 4.35
Total Protein, Visit 12 (Month 40), n=108	-1.9 ± 4.36
Total Protein, Visit 13 (Month 44), n=101	-1.8 ± 4.10
Total Protein, Visit 14 (Month 48), n=101	-2.0 ± 4.37
Total Protein, Visit 15 (Month 52), n=88	-1.9 ± 4.81
Total Protein, Visit 16 (Month 56), n=76	-2.1 ± 4.18
Total Protein, Visit 17 (Month 60), n=90	-2.4 ± 4.29
Total Protein, Visit 18 (Month 64), n=55	-2.2 ± 4.12
Total Protein, Visit 19 (Month 68), n=50	-2.2 ± 3.95
Total Protein, Visit 20 (Month 72), n=58	-3.0 ± 4.85
Total Protein, Visit 21 (Month 76), n=40	-1.8 ± 4.01
Total Protein, Visit 22 (Month 80), n=35	-0.6 ± 5.09
Total Protein, Visit 23 (Month 84), n=32	-2.2 ± 4.38
Total Protein, Visit 24 (Month 88), n=28	-1.9 ± 4.63
Total Protein, Visit 25 (Month 92), n=25	-1.2 ± 4.82
Total Protein, Visit 26 (Month 96), n=26	-1.1 ± 5.32
Total Protein, Visit 27 (Month 100), n=20	-0.9 ± 4.08
Total Protein, Visit 28 (Month 104), n=16	-0.2 ± 4.68
Total Protein, Visit 29 (Month 108), n=13	-2.1 ± 4.57
Total Protein, Visit 30 (Month 112), n=4	0.8 ± 2.36
Total Protein, Visit 31 (Month 116), n=3	-4.7 ± 0.58
Total Protein, Visit 32 (Month 120), n=1	-4.0 ± 99999
Total Protein, Follow up, n=261	-1.1 ± 4.75

Notes
[24] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, white blood cells (WBC)

Top of page

End point title

Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, white blood cells (WBC) ^[25]

End point description

Hematology parameters included eosinophils, basophils lymphocytes, monocytes, neutrophils, platelet count , and WBC. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[26]
Units: 10^9 cells per Liter
arithmetic mean (standard deviation)
Basophils, Visit 1 (Month 1), n=345	0.003 ± 0.0261
Basophils, Visit 1a (Month 2), n=64	0.013 ± 0.0340
Basophils, Visit 2 (Month 3), n=309	0.001 ± 0.0251
Basophils, Visit 2a (Month 4), n=82	0.021 ± 0.0488
Basophils, Visit 3 (Month 6), n=273	0.003 ± 0.0340
Basophils, Visit 3a (Month 8), n=97	0.005 ± 0.0300
Basophils, Visit 4 (Month 9), n=239	0.000 ± 0.0222
Basophils, Visit 4a (Month 10), n=111	0.003 ± 0.0276
Basophils, Visit 5 (Month 12), n=225	0.002 ± 0.0188
Basophils, Visit 6 (Month 16), n=198	0.002 ± 0.0215
Basophils, Visit 7 (Month 20), n=173	0.003 ± 0.0230
Basophils, Visit 8 (Month 24), n=159	0.001 ± 0.0205
Basophils, Visit 9 (Month 28), n=139	0.005 ± 0.0200
Basophils, Visit 10 (Month 32), n=125	0.008 ± 0.0229
Basophils, Visit 11 (Month 36), n=112	0.005 ± 0.0200
Basophils, Visit 12 (Month 40), n=108	0.007 ± 0.0253
Basophils, Visit 13 (Month 44), n=98	0.002 ± 0.0157
Basophils, Visit 14 (Month 48), n=100	0.002 ± 0.0201
Basophils, Visit 15 (Month 52), n=88	0.005 ± 0.0249
Basophils, Visit 16 (Month 56), n=75	0.006 ± 0.0245
Basophils, Visit 17 (Month 60), n=89	0.006 ± 0.0186
Basophils, Visit 18 (Month 64), n=51	0.005 ± 0.0334
Basophils, Visit 19 (Month 68), n=50	0.006 ± 0.0184
Basophils, Visit 20 (Month 72), n=54	0.005 ± 0.0173
Basophils, Visit 21 (Month 76), n=39	0.009 ± 0.0226
Basophils, Visit 22 (Month 80), n=35	0.004 ± 0.0140
Basophils, Visit 23 (Month 84), n=32	0.009 ± 0.0178
Basophils, Visit 24 (Month 88), n=27	0.004 ± 0.0189
Basophils, Visit 25 (Month 92), n=25	0.013 ± 0.0281
Basophils, Visit 26 (Month 96), n=24	0.010 ± 0.0254
Basophils, Visit 27 (Month 100), n=20	0.010 ± 0.0192
Basophils, Visit 28 (Month 104), n=16	0.008 ± 0.0118
Basophils, Visit 29 (Month 108), n=13	0.005 ± 0.0156
Basophils, Visit 30 (Month 112), n=4	0.003 ± 0.0171
Basophils, Visit 31 (Month 116), n=3	-0.003 ± 0.0153
Basophils, Visit 32 (Month 120), n=1	-0.020 ± 99999
Basophils, Follow up, n=252	0.001 ± 0.0236
Eosinophils, Visit 1 (Month 1), n=345	-0.006 ± 0.1045
Eosinophils, Visit 1a (Month 2), n=64	-0.018 ± 0.0982
Eosinophils, Visit 2 (Month 3), n=309	-0.006 ± 0.1061
Eosinophils, Visit 2a (Month 4), n=82	-0.002 ± 0.1274
Eosinophils, Visit 3 (Month 6), n=273	-0.009 ± 0.0941
Eosinophils, Visit 3a (Month 8), n=97	-0.010 ± 0.1142
Eosinophils, Visit 4 (Month 9), n=239	0.001 ± 0.1148
Eosinophils, Visit 4a (Month 10), n=111	-0.003 ± 0.1126
Eosinophils, Visit 5 (Month 12), n=225	-0.005 ± 0.1160
Eosinophils, Visit 6 (Month 16), n=198	-0.012 ± 0.1015
Eosinophils, Visit 7 (Month 20), n=173	-0.008 ± 0.1070
Eosinophils, Visit 8 (Month 24), n=159	-0.007 ± 0.0989
Eosinophils, Visit 9 (Month 28), n=139	-0.013 ± 0.0972
Eosinophils, Visit 10 (Month 32), n=125	-0.007 ± 0.0997
Eosinophils, Visit 11 (Month 36), n=112	-0.004 ± 0.1042
Eosinophils, Visit 12 (Month 40), n=108	-0.006 ± 0.1044
Eosinophils, Visit 13 (Month 44), n=98	-0.007 ± 0.0962
Eosinophils, Visit 14 (Month 48), n=100	-0.018 ± 0.0973
Eosinophils, Visit 15 (Month 52), n=88	-0.008 ± 0.1115
Eosinophils, Visit 16 (Month 56), n=75	-0.008 ± 0.1051
Eosinophils, Visit 17 (Month 60), n=88	0.009 ± 0.1214
Eosinophils, Visit 18 (Month 64), n=51	-0.001 ± 0.1298
Eosinophils, Visit 19 (Month 68), n=50	-0.008 ± 0.1335
Eosinophils, Visit 20 (Month 72), n=54	-0.002 ± 0.1235
Eosinophils, Visit 21 (Month 76), n=39	0.000 ± 0.1365
Eosinophils, Visit 22 (Month 80), n=35	0.000 ± 0.1352
Eosinophils, Visit 23 (Month 84), n=32	0.015 ± 0.1251
Eosinophils, Visit 24 (Month 88), n=27	-0.022 ± 0.1272
Eosinophils, Visit 25 (Month 92), n=25	-0.004 ± 0.1064
Eosinophils, Visit 26 (Month 96), n=24	-0.007 ± 0.1082
Eosinophils, Visit 27 (Month 100), n=20	0.032 ± 0.1637
Eosinophils, Visit 28 (Month 104), n=16	0.041 ± 0.1509
Eosinophils, Visit 29 (Month 108), n=13	0.062 ± 0.1678
Eosinophils, Visit 30 (Month 112), n=4	0.185 ± 0.1933
Eosinophils, Visit 31 (Month 116), n=3	0.043 ± 0.0603
Eosinophils, Visit 32 (Month 120), n=1	-0.020 ± 99999
Eosinophils, Follow up, n=252	-0.010 ± 0.1082
Lymphocytes, Visit 1 (Month 1), n=345	-0.127 ± 0.4854
Lymphocytes, Visit 1a (Month 2), n=64	-0.029 ± 0.5459
Lymphocytes, Visit 2 (Month 3), n=309	-0.147 ± 0.4446
Lymphocytes, Visit 2a (Month 4), n=82	-0.089 ± 0.5561
Lymphocytes, Visit 3 (Month 6), n=273	-0.124 ± 0.4476
Lymphocytes, Visit 3a (Month 8), n=97	-0.104 ± 0.4733
Lymphocytes, Visit 4 (Month 9), n=239	-0.137 ± 0.4833
Lymphocytes, Visit 4a (Month 10), n=111	0.007 ± 0.4505
Lymphocytes, Visit 5 (Month 12), n=225	-0.118 ± 0.4839
Lymphocytes, Visit 6 (Month 16), n=198	-0.130 ± 0.4605
Lymphocytes, Visit 7 (Month 20), n=173	-0.103 ± 0.4656
Lymphocytes, Visit 8 (Month 24), n=159	-0.091 ± 0.4387
Lymphocytes, Visit 9 (Month 28), n=139	-0.099 ± 0.4582
Lymphocytes, Visit 10 (Month 32), n=125	-0.103 ± 0.4502
Lymphocytes, Visit 11 (Month 36), n=112	-0.135 ± 0.4232
Lymphocytes, Visit 12 (Month 40), n=108	-0.114 ± 0.5521
Lymphocytes, Visit 13 (Month 44), n=98	-0.057 ± 0.4896
Lymphocytes, Visit 14 (Month 48), n=100	-0.117 ± 0.4672
Lymphocytes, Visit 15 (Month 52), n=88	-0.055 ± 0.4918
Lymphocytes, Visit 16 (Month 56), n=75	-0.049 ± 0.5077
Lymphocytes, Visit 17 (Month 60), n=88	-0.034 ± 0.5568
Lymphocytes, Visit 18 (Month 64), n=51	0.004 ± 0.5778
Lymphocytes, Visit 19 (Month 68), n=50	0.077 ± 0.5280
Lymphocytes, Visit 20 (Month 72), n=54	0.000 ± 0.5129
Lymphocytes, Visit 21 (Month 76), n=39	0.113 ± 0.5493
Lymphocytes, Visit 22 (Month 80), n=35	0.110 ± 0.5896
Lymphocytes, Visit 23 (Month 84), n=32	0.166 ± 0.4766
Lymphocytes, Visit 24 (Month 88), n=27	0.133 ± 0.5958
Lymphocytes, Visit 25 (Month 92), n=25	0.144 ± 0.3940
Lymphocytes, Visit 26 (Month 96), n=24	-0.001 ± 0.6195
Lymphocytes, Visit 27 (Month 100), n=20	0.172 ± 0.5272
Lymphocytes, Visit 28 (Month 104), n=16	0.141 ± 0.5226
Lymphocytes, Visit 29 (Month 108), n=13	0.193 ± 0.5144
Lymphocytes, Visit 30 (Month 112), n=4	0.278 ± 0.8945
Lymphocytes, Visit 31 (Month 116), n=3	0.367 ± 0.4038
Lymphocytes, Visit 32 (Month 120), n=1	-0.130 ± 99999
Lymphocytes, Follow up, n=252	0.022 ± 0.5031
Monocytes, Visit 1 (Month 1), n=345	0.024 ± 0.1425
Monocytes, Visit 1a (Month 2), n=64	0.085 ± 0.1846
Monocytes, Visit 2 (Month 3), n=309	0.017 ± 0.1580
Monocytes, Visit 2a (Month 4), n=82	0.071 ± 0.1850
Monocytes, Visit 3 (Month 6), n=273	0.022 ± 0.1610
Monocytes, Visit 3a (Month 8), n=97	0.073 ± 0.1581
Monocytes, Visit 4 (Month 9), n=239	0.022 ± 0.1518
Monocytes, Visit 4a (Month 10), n=111	0.080 ± 0.1653
Monocytes, Visit 5 (Month 12), n=225	0.028 ± 0.1563
Monocytes, Visit 6 (Month 16), n=198	0.023 ± 0.1598
Monocytes, Visit 7 (Month 20), n=173	0.019 ± 0.1661
Monocytes, Visit 8 (Month 24), n=159	0.038 ± 0.1840
Monocytes, Visit 9 (Month 28), n=139	0.056 ± 0.1646
Monocytes, Visit 10 (Month 32), n=125	0.047 ± 0.1597
Monocytes, Visit 11 (Month 36), n=112	0.049 ± 0.1649
Monocytes, Visit 12 (Month 40), n=108	0.040 ± 0.1750
Monocytes, Visit 13 (Month 44), n=98	0.037 ± 0.1780
Monocytes, Visit 14 (Month 48), n=100	0.033 ± 0.1442
Monocytes, Visit 15 (Month 52), n=88	0.065 ± 0.1720
Monocytes, Visit 16 (Month 56), n=75	0.043 ± 0.1632
Monocytes, Visit 17 (Month 60), n=88	0.044 ± 0.1736
Monocytes, Visit 18 (Month 64), n=51	0.028 ± 0.1644
Monocytes, Visit 19 (Month 68), n=50	0.027 ± 0.1253
Monocytes, Visit 20 (Month 72), n=54	0.039 ± 0.1201
Monocytes, Visit 21 (Month 76), n=39	0.078 ± 0.2002
Monocytes, Visit 22 (Month 80), n=35	0.046 ± 0.1629
Monocytes, Visit 23 (Month 84), n=32	0.064 ± 0.1596
Monocytes, Visit 24 (Month 88), n=27	0.065 ± 0.2083
Monocytes, Visit 25 (Month 92), n=25	0.057 ± 0.1956
Monocytes, Visit 26 (Month 96), n=24	0.035 ± 0.1405
Monocytes, Visit 27 (Month 100), n=20	0.119 ± 0.1604
Monocytes, Visit 28 (Month 104), n=16	0.039 ± 0.1903
Monocytes, Visit 29 (Month 108), n=13	0.068 ± 0.2342
Monocytes, Visit 30 (Month 112), n=4	0.030 ± 0.1985
Monocytes, Visit 31 (Month 116), n=3	-0.007 ± 0.0850
Monocytes, Visit 32 (Month 120), n=1	0.080 ± 99999
Monocytes, Follow up, n=252	0.022 ± 0.1754
Neutrophils, Visit 1 (Month 1), n=345	-0.143 ± 1.3093
Neutrophils, Visit 1a (Month 2), n=64	-0.142 ± 1.3123
Neutrophils, Visit 2 (Month 3), n=309	-0.045 ± 1.1768
Neutrophils, Visit 2a (Month 4), n=82	0.075 ± 1.4826
Neutrophils, Visit 3 (Month 6), n=273	-0.087 ± 1.3700
Neutrophils, Visit 3a (Month 8), n=97	-0.098 ± 1.3412
Neutrophils, Visit 4 (Month 9), n=239	0.032 ± 1.1933
Neutrophils, Visit 4a (Month 10), n=111	0.203 ± 1.3922
Neutrophils, Visit 5 (Month 12), n=225	0.015 ± 1.6014
Neutrophils, Visit 6 (Month 16), n=198	0.086 ± 1.3107
Neutrophils, Visit 7 (Month 20), n=173	0.121 ± 1.2780
Neutrophils, Visit 8 (Month 24), n=159	0.368 ± 1.4584
Neutrophils, Visit 9 (Month 28), n=139	0.188 ± 1.2575
Neutrophils, Visit 10 (Month 32), n=125	0.118 ± 1.1824
Neutrophils, Visit 11 (Month 36), n=112	0.057 ± 1.2868
Neutrophils, Visit 12 (Month 40), n=108	0.196 ± 1.1770
Neutrophils, Visit 13 (Month 44), n=98	0.243 ± 1.4180
Neutrophils, Visit 14 (Month 48), n=100	0.095 ± 1.2410
Neutrophils, Visit 15 (Month 52), n=88	0.432 ± 1.4504
Neutrophils, Visit 16 (Month 56), n=75	0.412 ± 1.4045
Neutrophils, Visit 17 (Month 60), n=88	0.416 ± 1.3905
Neutrophils, Visit 18 (Month 64), n=51	0.296 ± 1.2674
Neutrophils, Visit 19 (Month 68), n=50	0.436 ± 1.0379
Neutrophils, Visit 20 (Month 72), n=54	0.552 ± 1.3322
Neutrophils, Visit 21 (Month 76), n=39	0.639 ± 1.5548
Neutrophils, Visit 22 (Month 80), n=35	0.346 ± 1.3809
Neutrophils, Visit 23 (Month 84), n=32	0.560 ± 1.4536
Neutrophils, Visit 24 (Month 88), n=27	0.366 ± 1.8672
Neutrophils, Visit 25 (Month 92), n=25	0.130 ± 1.9387
Neutrophils, Visit 26 (Month 96), n=24	0.707 ± 1.7085
Neutrophils, Visit 27 (Month 100), n=20	0.247 ± 1.6045
Neutrophils, Visit 28 (Month 104), n=16	0.458 ± 1.1406
Neutrophils, Visit 29 (Month 108), n=13	-0.027 ± 1.4607
Neutrophils, Visit 30 (Month 112), n=4	0.658 ± 1.2219
Neutrophils, Visit 31 (Month 116), n=3	0.297 ± 0.5320
Neutrophils, Visit 32 (Month 120), n=1	0.470 ± 99999
Neutrophils, Follow up, n=252	-0.010 ± 1.5258
Platelet Count, Visit 1 (Month 1), n=345	0.9 ± 40.69
Platelet count, Visit 1a (Month 2), n=65	6.4 ± 41.67
Platelet count, Visit 2 (Month 3), n=311	0.7 ± 37.59
Platelet count, Visit 2a (Month 4), n=82	12.7 ± 37.26
Platelet count, Visit 3 (Month 6), n=273	-1.7 ± 41.28
Platelet count, Visit 3a (Month 8), n=99	-5.3 ± 31.49
Platelet count, Visit 4 (Month 9), n=241	-7.1 ± 37.88
Platelet count, Visit 4a (Month 10), n=108	-2.8 ± 38.71
Platelet count, Visit 5 (Month 12), n=225	-8.6 ± 35.57
Platelet count, Visit 6 (Month 16), n=196	-9.0 ± 43.09
Platelet count, Visit 7 (Month 20), n=171	-15.8 ± 41.13
Platelet count, Visit 8 (Month 24), n=162	-17.3 ± 44.99
Platelet count, Visit 9 (Month 28), n=137	-18.0 ± 44.47
Platelet count, Visit 10 (Month 32), n=124	-20.8 ± 38.96
Platelet count, Visit 11 (Month 36), n=114	-25.8 ± 42.66
Platelet count, Visit 12 (Month 40), n=108	-24.3 ± 39.96
Platelet count, Visit 13 (Month 44), n=98	-22.4 ± 37.92
Platelet count, Visit 14 (Month 48), n=98	-25.2 ± 37.88
Platelet count, Visit 15 (Month 52), n=84	-22.3 ± 40.93
Platelet count, Visit 16 (Month 56), n=75	-17.1 ± 50.19
Platelet count, Visit 17 (Month 60), n=88	-18.6 ± 46.11
Platelet count, Visit 18 (Month 64), n=54	-23.1 ± 38.78
Platelet count, Visit 19 (Month 68), n=50	-17.7 ± 42.66
Platelet count, Visit 20 (Month 72), n=53	-20.4 ± 51.90
Platelet count, Visit 21 (Month 76), n=40	-11.1 ± 55.97
Platelet count, Visit 22 (Month 80), n=34	-10.0 ± 57.22
Platelet count, Visit 23 (Month 84), n=31	-7.0 ± 50.20
Platelet count, Visit 24 (Month 88), n=25	-22.1 ± 29.77
Platelet count, Visit 25 (Month 92), n=25	-16.8 ± 40.54
Platelet count, Visit 26 (Month 96), n=24	-4.9 ± 43.76
Platelet count, Visit 27 (Month 100), n=20	1.9 ± 45.98
Platelet count, Visit 28 (Month 104), n=16	-6.3 ± 44.81
Platelet count, Visit 29 (Month 108), n=13	-9.5 ± 41.54
Platelet count, Visit 30 (Month 112), n=4	10.0 ± 32.44
Platelet count, Visit 31 (Month 116), n=3	-5.7 ± 30.09
Platelet count, Visit 32 (Month 120), n=1	25.0 ± 99999
Platelet count, Follow up, n=249	-9.4 ± 49.63
WBC, Visit 1 (Month 1), n=349	-0.25 ± 1.403
WBC, Visit 1a (Month 2), n=65	-0.11 ± 1.478
WBC, Visit 2 (Month 3), n=315	-0.22 ± 1.371
WBC, Visit 2a (Month 4), n=82	0.07 ± 1.648
WBC, Visit 3 (Month 6), n=278	-0.20 ± 1.531
WBC, Visit 3a (Month 8), n=99	-0.15 ± 1.537
WBC, Visit 4 (Month 9), n=244	-0.08 ± 1.356
WBC, Visit 4a (Month 10), n=113	0.28 ± 1.608
WBC, Visit 5 (Month 12), n=226	-0.09 ± 1.690
WBC, Visit 6 (Month 16), n=199	-0.06 ± 1.385
WBC, Visit 7 (Month 20), n=174	0.01 ± 1.468
WBC, Visit 8 (Month 24), n=164	0.25 ± 1.655
WBC, Visit 9 (Month 28), n=142	0.10 ± 1.367
WBC, Visit 10 (Month 32), n=126	0.09 ± 1.374
WBC, Visit 11 (Month 36), n=115	-0.05 ± 1.387
WBC, Visit 12 (Month 40), n=109	0.10 ± 1.514
WBC, Visit 13 (Month 44), n=98	0.21 ± 1.687
WBC, Visit 14 (Month 48), n=101	-0.01 ± 1.381
WBC, Visit 15 (Month 52), n=88	0.43 ± 1.648
WBC, Visit 16 (Month 56), n=76	0.37 ± 1.603
WBC, Visit 17 (Month 60), n=89	0.41 ± 1.663
WBC, Visit 18 (Month 64), n=54	0.33 ± 1.613
WBC, Visit 19 (Month 68), n=50	0.54 ± 1.376
WBC, Visit 20 (Month 72), n=55	0.57 ± 1.532
WBC, Visit 21 (Month 76), n=40	0.81 ± 1.940
WBC, Visit 22 (Month 80), n=35	0.52 ± 1.622
WBC, Visit 23 (Month 84), n=32	0.83 ± 1.599
WBC, Visit 24 (Month 88), n=27	0.57 ± 1.964
WBC, Visit 25 (Month 92), n=25	0.34 ± 2.114
WBC, Visit 26 (Month 96), n=24	0.75 ± 1.670
WBC, Visit 27 (Month 100), n=20	0.59 ± 1.809
WBC, Visit 28 (Month 104), n=16	0.70 ± 1.372
WBC, Visit 29 (Month 108), n=13	0.30 ± 1.614
WBC, Visit 30 (Month 112), n=4	1.18 ± 1.864
WBC, Visit 31 (Month 116), n=3	0.70 ± 0.800
WBC, Visit 32 (Month 120), n=1	0.40 ± 99999
WBC, Follow up, n=255	0.02 ± 1.738

Notes
[26] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in hematocrit

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End point title

Change from Baseline in hematocrit ^[27]

End point description

Blood samples for the assessment of clinical laboratory parameter hematocrit were collected at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[28]
Units: Percentage of red blood cells in blood
arithmetic mean (standard deviation)
Hematocrit, Visit 1 (Month 1), n=340	-0.009 ± 0.0215
Hematocrit, Visit 1a (Month 2), n=63	-0.005 ± 0.0227
Hematocrit, Visit 2 (Month 3), n=308	-0.004 ± 0.0229
Hematocrit, Visit 2a (Month 4), n=79	-0.012 ± 0.0230
Hematocrit, Visit 3 (Month 6), n=274	-0.005 ± 0.0244
Hematocrit, Visit 3a (Month 8), n=95	-0.009 ± 0.0264
Hematocrit, Visit 4 (Month 9), n=231	-0.002 ± 0.0263
Hematocrit, Visit 4a (Month 10), n=111	-0.004 ± 0.0254
Hematocrit, Visit 5 (Month 12), n=223	-0.004 ± 0.0256
Hematocrit, Visit 6 (Month 16), n=196	-0.003 ± 0.0270
Hematocrit, Visit 7 (Month 20), n=166	-0.001 ± 0.0255
Hematocrit, Visit 8 (Month 24), n=160	0.000 ± 0.0275
Hematocrit, Visit 9 (Month 28), n=141	0.005 ± 0.0260
Hematocrit, Visit 10 (Month 32), n=122	0.004 ± 0.0285
Hematocrit, Visit 11 (Month 36), n=113	-0.001 ± 0.0301
Haematocrit, Visit 12 (Month 40), n=106	0.006 ± 0.0301
Hematocrit, Visit 13 (Month 44), n=95	0.003 ± 0.0274
Hematocrit, Visit 14 (Month 48), n=100	-0.003 ± 0.0286
Hematocrit, Visit 15 (Month 52), n=88	-0.001 ± 0.0289
Hematocrit, Visit 16 (Month 56), n=74	-0.001 ± 0.0230
Haematocrit, Visit 17 (Month 60), n=88	0.000 ± 0.0314
Hematocrit, Visit 18 (Month 64), n=51	0.009 ± 0.0270
Hematocrit, Visit 19 (Month 68), n=50	0.008 ± 0.0278
Hematocrit, Visit 20 (Month 72), n=55	0.004 ± 0.0287
Hematocrit, Visit 21 (Month 76), n=39	0.010 ± 0.0377
Hematocrit, Visit 22 (Month 80), n=34	0.015 ± 0.0303
Hematocrit, Visit 23 (Month 84), n=30	0.000 ± 0.0344
Hematocrit, Visit 24 (Month 88), n=26	0.005 ± 0.0294
Hematocrit, Visit 25 (Month 92), n=24	0.016 ± 0.0264
Hematocrit, Visit 26 (Month 96), n=24	0.013 ± 0.0258
Hematocrit, Visit 27 (Month 100), n=20	0.016 ± 0.0201
Hematocrit, Visit 28 (Month 104), n=16	0.016 ± 0.0203
Hematocrit, Visit 29 (Month 108), n=13	-0.002 ± 0.0268
Hematocrit, Visit 30 (Month 112), n=4	0.000 ± 0.0365
Hematocrit, Visit 31 (Month 116), n=3	0.033 ± 0.0666
Hematocrit, Visit 32 (Month 120), n=1	0.080 ± 99999
Hematocrit,Follow up, n=253	0.003 ± 0.0262

Notes
[28] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in hemoglobin

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End point title

Change from Baseline in hemoglobin ^[29]

End point description

The hematology parameters included hemoglobin. The clinical laboratory evaluations were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[30]
Units: Grams per liter
arithmetic mean (standard deviation)
Hemoglobin, Visit 1 (Month 1), n=349	-2.6 ± 6.96
Hemoglobin, Visit 1a (Month 2), n=65	-1.8 ± 7.30
Hemoglobin, Visit 2 (Month 3), n=316	-0.8 ± 7.89
Hemoglobin, Visit 2a (Month 4), n=82	-3.3 ± 8.11
Hemoglobin, Visit 3 (Month 6), n=279	-1.3 ± 8.21
Hemoglobin, Visit 3a (Month 8), n=99	-3.0 ± 8.70
Hemoglobin, Visit 4 (Month 9), n=244	-0.7 ± 8.87
Hemoglobin, Visit 4a (Month 10), n=113	-2.0 ± 8.41
Hemoglobin, Visit 5 (Month 12), n=226	-1.4 ± 8.64
Hemoglobin, Visit 6 (Month 16), n=199	-0.4 ± 8.83
Hemoglobin, Visit 7 (Month 20), n=174	-0.6 ± 9.01
Hemoglobin, Visit 8 (Month 24), n=164	-0.3 ± 8.58
Hemoglobin, Visit 9 (Month 28), n=142	1.2 ± 8.99
Hemoglobin, Visit 10 (Month 32), n=126	0.3 ± 9.58
Hemoglobin, Visit 11 (Month 36), n=115	-1.0 ± 10.12
Hemoglobin, Visit 12 (Month 40), n=109	0.4 ± 9.78
Hemoglobin, Visit 13 (Month 44), n=98	-0.1 ± 9.44
Hemoglobin, Visit 14 (Month 48), n=101	-1.6 ± 9.57
Hemoglobin, Visit 15 (Month 52), n=88	-1.6 ± 9.75
Hemoglobin, Visit 16 (Month 56), n=76	-2.3 ± 7.47
Hemoglobin, Visit 17 (Month 60), n=89	-2.4 ± 10.14
Hemoglobin, Visit 18 (Month 64), n=54	-1.1 ± 8.76
Hemoglobin, Visit 19 (Month 68), n=50	-0.4 ± 9.42
Hemoglobin, Visit 20 (Month 72), n=55	-2.5 ± 10.78
Hemoglobin, Visit 21 (Month 76), n=40	-1.5 ± 11.67
Hemoglobin, Visit 22 (Month 80), n=35	-0.8 ± 9.66
Hemoglobin, Visit 23 (Month 84), n=32	-3.6 ± 11.61
Hemoglobin, Visit 24 (Month 88), n=27	-3.0 ± 9.46
Hemoglobin, Visit 25 (Month 92), n=25	-2.3 ± 8.09
Hemoglobin, Visit 26 (Month 96), n=24	-4.0 ± 8.26
Hemoglobin, Visit 27 (Month 100), n=20	-2.8 ± 5.82
Hemoglobin, Visit 28 (Month 104), n=16	-2.9 ± 9.54
Hemoglobin, Visit 29 (Month 108), n=13	-8.1 ± 8.56
Hemoglobin, Visit 30 (Month 112), n=4	-12.5 ± 6.14
Hemoglobin, Visit 31 (Month 116), n=3	3.0 ± 22.52
Hemoglobin, Visit 32 (Month 120), n=1	25.0 ± 99999
Hemoglobin, Follow up, n=256	-0.1 ± 8.89

Notes
[30] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in hematology parameter red blood cells (RBC)

Top of page

End point title

Change from Baseline in hematology parameter red blood cells (RBC) ^[31]

End point description

The hematology parameters included RBC. The clinical laboratory evaluation were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[32]
Units: 10^12 cells per liter
arithmetic mean (standard deviation)
RBC, Visit 1 (Month 1), n=349	-0.07 ± 0.226
RBC, Visit 1a (Month 2), n=65	0.00 ± 0.236
RBC, Visit 2 (Month 3), n=316	-0.02 ± 0.237
RBC, Visit 2a (Month 4), n=82	-0.06 ± 0.233
RBC, Visit 3 (Month 6), n=279	-0.04 ± 0.243
RBC, Visit 3a (Month 8), n=99	-0.05 ± 0.269
RBC, Visit 4 (Month 9), n=244	-0.03 ± 0.256
RBC, Visit 4a (Month 10), n=113	-0.02 ± 0.235
RBC, Visit 5 (Month 12), n=226	-0.04 ± 0.255
RBC, Visit 6 (Month 16), n=199	-0.01 ± 0.264
RBC, Visit 7 (Month 20), n=174	-0.02 ± 0.243
RBC, Visit 8 (Month 24), n=164	-0.03 ± 0.281
RBC, Visit 9 (Month 28), n=142	0.00 ± 0.271
RBC, Visit 10 (Month 32), n=126	-0.05 ± 0.286
RBC, Visit 11 (Month 36), n=115	-0.09 ± 0.283
RBC, Visit 12 (Month 40), n=109	-0.02 ± 0.275
RBC, Visit 13 (Month 44), n=98	-0.06 ± 0.287
RBC, Visit 14 (Month 48), n=101	-0.10 ± 0.280
RBC, Visit 15 (Month 52), n=88	-0.08 ± 0.285
RBC, Visit 16 (Month 56), n=76	-0.08 ± 0.252
RBC, Visit 17 (Month 60), n=89	-0.07 ± 0.323
RBC, Visit 18 (Month 64), n=54	-0.01 ± 0.263
RBC, Visit 19 (Month 68), n=50	0.01 ± 0.255
RBC, Visit 20 (Month 72), n=55	-0.03 ± 0.239
RBC, Visit 21 (Month 76), n=40	0.02 ± 0.346
RBC, Visit 22 (Month 80), n=35	0.09 ± 0.338
RBC, Visit 23 (Month 84), n=32	0.00 ± 0.290
RBC, Visit 24 (Month 88), n=27	0.00 ± 0.314
RBC, Visit 25 (Month 92), n=25	0.05 ± 0.337
RBC, Visit 26 (Month 96), n=24	0.06 ± 0.317
RBC, Visit 27 (Month 100), n=20	0.13 ± 0.251
RBC, Visit 28 (Month 104), n=16	0.14 ± 0.365
RBC, Visit 29 (Month 108), n=13	-0.04 ± 0.328
RBC, Visit 30 (Month 112), n=4	0.08 ± 0.386
RBC, Visit 31 (Month 116), n=3	0.10 ± 0.346
RBC, Visit 32 (Month 120), n=1	0.00 ± 99999
RBC, Follow up, n=256	-0.01 ± 0.263

Notes
[32] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in urine specific gravity

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End point title

Change from Baseline in urine specific gravity ^[33]

End point description

Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. Urinalysis assessments were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[34]
Units: Ratio
arithmetic mean (standard deviation)
Specific gravity, Visit 1 (Month 1), n=348	-0.0011 ± 0.00936
Specific gravity, Visit 1a (Month 2), n=1	0.0000 ± 99999
Specific gravity, Visit 2 (Month 3), n=312	-0.0011 ± 0.00918
Specific gravity, Visit 3 (Month 6), n=270	0.0003 ± 0.00896
Specific gravity, Visit 4 (Month 9), n=243	0.0002 ± 0.00984
Specific gravity, Visit 5 (Month 12), n=221	-0.0010 ± 0.01014
Specific gravity, Visit 6 (Month 16), n=196	0.0006 ± 0.01016
Specific gravity, Visit 7 (Month 20), n=170	0.0015 ± 0.00901
Specific gravity, Visit 8 (Month 24), n=157	0.0002 ± 0.01015
Specific gravity, Visit 9 (Month 28), n=137	0.0007 ± 0.00922
Specific gravity, Visit 10 (Month 32), n=124	0.0001 ± 0.00986
Specific gravity, Visit 11 (Month 36), n=111	-0.0016 ± 0.01058
Specific gravity, Visit 12 (Month 40), n=106	0.0004 ± 0.01007
Specific gravity, Visit 13 (Month 44), n=97	0.0004 ± 0.00944
Specific gravity, Visit 14 (Month 48), n=99	0.0000 ± 0.01019
Specific gravity, Visit 15 (Month 52), n=83	-0.0100 ± 0.10022
Specific gravity, Visit 16 (Month 56), n=71	0.0003 ± 0.01089
Specific gravity, Visit 17 (Month 60), n=84	-0.0008 ± 0.01022
Specific gravity, Visit 18 (Month 64), n=53	0.0006 ± 0.00894
Specific gravity, Visit 19 (Month 68), n=50	0.0014 ± 0.01052
Specific gravity, Visit 20 (Month 72), n=55	-0.0021 ± 0.00882
Specific gravity, Visit 21 (Month 76), n=39	0.0030 ± 0.00837
Specific gravity, Visit 22 (Month 80), n=35	0.0015 ± 0.00939
Specific gravity, Visit 23 (Month 84), n=31	0.0024 ± 0.00917
Specific gravity, Visit 24 (Month 88), n=28	0.0043 ± 0.00994
Specific gravity, Visit 25 (Month 92), n=25	0.0046 ± 0.00861
Specific gravity, Visit 26 (Month 96), n=26	0.0035 ± 0.00857
Specific gravity, Visit 27 (Month 100), n=20	0.0029 ± 0.00718
Specific gravity, Visit 28 (Month 104), n=16	0.0026 ± 0.00713
Specific gravity, Visit 29 (Month 108), n=13	0.0020 ± 0.00709
Specific gravity, Visit 30 (Month 112), n=4	0.0020 ± 0.00673
Specific gravity, Visit 31 (Month 116), n=3	0.0030 ± 0.01082
Specific gravity, Visit 32 (Month 120), n=1	-0.0010 ± 99999
Specific gravity, Follow up, n=247	0.0008 ± 0.00889

Notes
[34] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in urine potential of hydrogen (pH)

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End point title

Change from Baseline in urine potential of hydrogen (pH) ^[35]

End point description

Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. Urinalysis assessments were performed at all study visits during the Open-Label Treatment Phase. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[36]
Units: Unit on a pH scale
arithmetic mean (standard deviation)
pH, Visit 1 (Month 1), n=349	-0.13 ± 0.685
pH, Visit 1a (Month 2), n=1	0.50 ± 99999
pH, Visit 2 (Month 3), n=313	-0.09 ± 0.699
pH, Visit 3 (Month 6), n=270	-0.07 ± 0.634
pH, Visit 4 (Month 9), n=245	0.02 ± 0.633
pH, Visit 5 (Month 12), n=222	-0.02 ± 0.616
pH, Visit 6 (Month 16), n=196	0.07 ± 0.651
pH, Visit 7 (Month 20), n=170	0.04 ± 0.686
pH, Visit 8 (Month 24), n=158	0.09 ± 0.672
pH, Visit 9 (Month 28), n=138	0.17 ± 0.787
pH, Visit 10 (Month 32), n=124	0.17 ± 0.715
pH, Visit 11 (Month 36), n=111	0.26 ± 0.663
pH, Visit 12 (Month 40), n=107	0.30 ± 0.700
pH, Visit 13 (Month 44), n=97	0.36 ± 0.736
pH, Visit 14 (Month 48), n=99	0.38 ± 0.722
pH, Visit 15 (Month 52), n=83	0.27 ± 0.621
pH, Visit 16 (Month 56), n=71	0.34 ± 0.840
pH, Visit 17 (Month 60), n=84	0.32 ± 0.662
pH, Visit 18 (Month 64), n=53	0.33 ± 0.627
pH, Visit 19 (Month 68), n=50	0.42 ± 0.785
pH, Visit 20 (Month 72), n=55	0.27 ± 0.686
pH, Visit 21 (Month 76), n=39	0.36 ± 0.688
pH, Visit 22 (Month 80), n=35	0.23 ± 0.657
pH, Visit 23 (Month 84), n=31	0.35 ± 0.661
pH, Visit 24 (Month 88), n=28	0.29 ± 0.517
pH, Visit 25 (Month 92), n=25	0.36 ± 0.621
pH, Visit 26 (Month 96), n=26	0.21 ± 0.551
pH, Visit 27 (Month 100), n=20	0.45 ± 0.724
pH, Visit 28 (Month 104), n=16	0.13 ± 0.342
pH, Visit 29 (Month 108), n=13	0.77 ± 0.753
pH, Visit 30 (Month 112), n=4	0.50 ± 0.577
pH, Visit 31 (Month 116), n=3	-0.17 ± 0.764
pH, Visit 32 (Month 120), n=1	0.00 ± 99999
pH, Follow up, n=248	0.22 ± 0.746

Notes
[36] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in Post-Void Residual (PVR) bladder ultrasound volume

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End point title

Change from Baseline in Post-Void Residual (PVR) bladder ultrasound volume ^[37]

End point description

The post-void residual urine volume in the bladder was evaluated by transabdominal ultrasound. The urine bladder was sonicated from two directions perpendicular to one another, and the volume calculated automatically. A PVR bladder ultrasound to assess urinary retention was performed during the first year at Months 1, 3 and 12 and at the end of each 12 month study cycle that the participant was enrolled (i.e.,second year, third year, fourth year, etc.) in the Open-Label Treatment Phase of the study. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category title).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[38]
Units: Milliliters
arithmetic mean (standard deviation)
PVR urine volume, Visit 1 (Month 1), n=337	4.6 ± 52.10
PVR urine volume, Visit 2 (Month 3), n=307	4.1 ± 40.88
PVR urine volume, Visit 5 (Month 12), n=223	4.1 ± 52.38
PVR urine volume, Visit 8 (Month 24), n=111	5.5 ± 67.28
PVR urine volume, Visit 11 (Month 36), n=106	5.0 ± 46.29
PVR urine volume, Visit 14 (Month 48), n=96	-2.3 ± 39.69
PVR urine volume, Visit 17 (Month 60), n=77	22.2 ± 87.43
PVR urine volume, Visit 20 (Month 72), n=53	7.1 ± 49.87
PVR urine volume, Visit 23 (Month 84), n=29	15.7 ± 74.06
PVR urine volume, Visit 26 (Month 96), n=24	2.0 ± 38.54
PVR urine volume, Visit 29 (Month 108), n=10	21.9 ± 63.58
PVR urine volume, Follow up, n=186	-4.0 ± 47.11

Notes
[38] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in the urinary voiding function [UVF] (assessed using the American Urological Association [AUA] Symptom Index)

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End point title

Change from Baseline in the urinary voiding function [UVF] (assessed using the American Urological Association [AUA] Symptom Index) ^[39]

End point description

AUA Symptom Index was completed during the first year at Months 1, 3, 12 and at the end of each 12 month study cycle that the participant was enrolled in the Open-Label Treatment Phase (second, third, fourth year) to assess the participant UVF. The questions were scored on a scale of 0 to 5, with 0 (not at all) to 5 (almost always). A Symptom Index is determined by adding the scores. The lowest possible score is 0 and the highest possible score is 35, which would represent the highest level of pain and discomfort. Baseline assessment in this OLE study was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed represented by (n=x).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[40]
Units: Scores on a scale
arithmetic mean (standard deviation)
AUA Overall Score, Visit 1 (Month 1), n=348	-0.4 ± 3.82
AUA Overall Score, Visit 2 (Month 3), n=325	-0.5 ± 3.80
AUA Overall Score, Visit 5 (Month 12), n=228	-0.5 ± 3.58
AUA Overall Score, Visit 8 (Month 24), n=114	-0.5 ± 3.84
AUA Overall Score, Visit 11 (Month 36), n=115	-0.3 ± 5.22
AUA Overall Score, Visit 14 (Month 48), n=102	-0.6 ± 4.89
AUA Overall Score, Visit 17 (Month 60), n=87	-0.4 ± 5.02
AUA Overall Score, Visit 20 (Month 72), n=56	-0.1 ± 5.52
AUA Overall Score, Visit 23 (Month 84), n=32	0.8 ± 6.61
AUA Overall Score, Visit 26 (Month 96), n=26	0.5 ± 5.58
AUA Overall Score, Visit 29 (Month 108), n=13	0.0 ± 1.68
AUA Overall Score, Visit 32 (Month 120), n=1	0.0 ± 99999
AUA Overall Score, Follow up, n=217	0.0 ± 4.43

Notes
[40] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire

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End point title

Change from Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire ^[41]

End point description

The QOLIE-31-P questionnaire contained 30 items. The subscale scores (seizure worry, overall QOL, emotional well-being, energy-fatigue, cognitive, medication effects, social functioning), the final QOLIE-31-P score and the weighted total score (overall assessment) were calculated according to the scoring algorithm defined by the author. Scores range from 0 to 100 with higher scores indicating better function. Baseline was defined as the last assessment of that endpoint in VRX-RET-E22-302 taken prior to the first active treatment with retigabine. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline values. 99999 indicates standard deviation could not be calculated as only 1 participant was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[42]
Units: Scores on a scale
arithmetic mean (standard deviation)
Final QOLIE-31-P Score, Visit 2 (Month 3), n=296	1.33 ± 14.409
Final QOLIE-31-P Score, Visit 3 (Month 6), n=262	0.87 ± 14.618
Final QOLIE-31-P Score, Visit 4 (Month 9), n=229	0.27 ± 14.365
Final QOLIE-31-P Score, Visit 5 (Month 12), n=214	1.24 ± 14.498
Final QOLIE-31-P Score, Visit 8 (Month 24), n=142	3.76 ± 12.406
Final QOLIE-31-P Score, Visit 11 (Month 36), n=97	2.77 ± 13.784
Final QOLIE-31-P Score, Visit 14 (Month 48), n=83	0.78 ± 13.976
Final QOLIE-31-P Score Visit 17 (Month 60), n=68	2.37 ± 15.197
Final QOLIE-31-P Score Visit 20 (Month 72), n=47	3.07 ± 16.172
Final QOLIE-31-P Score Visit 23 (Month 84), n=26	4.31 ± 13.849
Final QOLIE-31-P Score Visit 26 (Month 96), n=24	4.07 ± 11.745
Final QOLIE-31-P Score Visit 29 (Month 108), n=12	6.35 ± 14.783
Final QOLIE-31-P Score Visit 32 (Month 120), n=1	14.36 ± 99999
Final QOLIE-31-P Score, Follow up, n=224	-0.83 ± 14.256

Notes
[42] - Safety Population

No statistical analyses for this end point

Primary: Percentage of participants with Abnormal Results of Physical Examination

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End point title

Percentage of participants with Abnormal Results of Physical Examination ^[43]

End point description

A complete physical examination was performed at the end of each 12 month study cycle (i.e., first year, second year, third year, etc.) during the Open-Label Treatment Phase. The investigator assessed the skin at every clinic visit. If abnormal skin discoloration was confirmed, the participant continued to be followed by the dermatologist. If the abnormal skin discoloration was not confirmed, the investigator resumed assessing the participants skin at all scheduled clinic visits. Only data for abnormal values on physical examination have been presented. Only those participants available at the specified time points were analyzed.

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[44]
Units: Percentage of participants
Visit 5 (Month 12), n=234	18
Visit 8 (Month 24), n=166	17
Visit 11 (Month 36), n=121	21
Visit 14 (Month 48), n=104	19
Visit 17 (Month 60), n=88	19
Visit 20 (Month 72), n=58	24
Visit 23 (Month 84), n=32	34
Visit 26 (Month 96), n=26	35
Visit 29 (Month 108), n=13	38
Follow up visit, n=260	27

Notes
[44] - Safety Population

No statistical analyses for this end point

Primary: Percentage of participants with Abnormal Results of Neurological Examination

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End point title

Percentage of participants with Abnormal Results of Neurological Examination ^[45]

End point description

A complete neurological examination was performed at the end of each 12 month study cycle (i.e., first year, second year, third year, etc.) during the Open-Label Treatment Phase. Abnormal results were categorized as Abnormal-Not Clinically Significant (A-NCS) and Abnormal and Clinically Significant (A-CS). Only data for abnormal values on neurological examination have been presented. Only those participants available at the specified time points were analyzed.

End point type

Primary

End point timeframe

Baseline and up to 122 months

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Retigabine
Number of subjects analysed	376 ^[46]
Units: Percentage of participants
Visit 1 (Month 1), A-NCS, n=356	23
Visit 1 (Month 1), A-CS, n=356	10
Visit 2 (Month 3), A-NCS, n=328	23
Visit 2 (Month 3), A-CS, n=328	9
Visit 3 (Month 6), A-NCS, n=287	22
Visit 3 (Month 6), A-CS, n=287	10
Visit 4 (Month 9), A-NCS, n=252	23
Visit 4 (Month 9), A-CS, n=252	11
Visit 5 (Month 12), A-NCS, n=234	27
Visit 5 (Month 12), A-CS, n=234	12
Visit 6 (Month 16), A-NCS, n=202	24
Visit 6 (Month 16), A-CS, n=202	9
Visit 7 (Month 20), A-NCS, n=179	25
Visit 7 (Month 20), A-CS, n=179	9
Visit 8 (Month 24), A-NCS, n=166	34
Visit 8 (Month 24), A-CS, n=166	10
Visit 9 (Month 28), A-NCS, n=146	32
Visit 9 (Month 28), A-CS, n=146	8
Visit 10 (Month 32), A-NCS, n=127	32
Visit 10 (Month 32), A-CS, n=127	8
Visit 11 (Month 36), A-NCS, n=121	35
Visit 11 (Month 36), A-CS, n=121	8
Visit 12 (Month 40), A-NCS, n=112	28
Visit 12 (Month 40), A-CS, n=112	10
Visit 13 (Month 44), A-NCS, n=105	31
Visit 13 (Month 44), A-CS, n=105	9
Visit 14 (Month 48), A-NCS, n=104	28
Visit 14 (Month 48), A-CS, n=104	11
Visit 15 (Month 52), A-NCS, n=91	31
Visit 15 (Month 52), A-CS, n=91	9
Visit 16 (Month 56), A-NCS, n=77	32
Visit 16 (Month 56), A-CS, n=77	9
Visit 17 (Month 60), A-NCS, n=89	29
Visit 17 (Month 60), A-CS, n=89	9
Visit 18 (Month 64), A-NCS, n=58	29
Visit 18 (Month 64), A-CS, n=58	10
Visit 19 (Month 68), A-NCS, n=53	36
Visit 19 (Month 68), A-CS, n=53	9
Visit 20 (Month 72), A-NCS, n=59	41
Visit 20 (Month 72), A-CS, n=59	7
Visit 21 (Month 76), A-NCS, n=43	40
Visit 21 (Month 76), A-CS, n=43	7
Visit 22 (Month 80), A-NCS, n=37	41
Visit 22 (Month 80), A-CS, n=37	5
Visit 23 (Month 84), A-NCS, n=32	47
Visit 23 (Month 84), A-CS, n=32	3
Visit 24 (Month 88), A-NCS, n=29	45
Visit 24 (Month 88), A-CS, n=29	7
Visit 25 (Month 92), A-NCS, n=25	40
Visit 25 (Month 92), A-CS, n=25	8
Visit 26 (Month 96), A-NCS, n=26	42
Visit 26 (Month 96), A-CS, n=26	15
Visit 27 (Month 100), A-NCS, n=19	21
Visit 27 (Month 100), A-CS, n=19	16
Visit 28 (Month 104), A-NCS, n=17	24
Visit 28 (Month 104), A-CS, n=17	24
Visit 29 (Month 108), A-NCS, n=13	31
Visit 29 (Month 108), A-CS, n=13	8
Follow up visit, A-NCS, n=263	22
Follow up visit, A-CS, n=263	8

Notes
[46] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with retinal pigmentary abnormalities (RPA)

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End point title

Percentage of participants with retinal pigmentary abnormalities (RPA)

End point description

RPA was determined by either an ophthalmologist or retina specialist. RPA is the composite endpoint assessed by its components: pigmentary abnormalities (PA) in the macula, PA in the peripheral retina (PR), PA in both macula and PR and PA at location unspecified. Only those participants with >=1 ophthalmology exam on or before last dose of retigabine are presented..

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	54 ^[47]
Units: Percentage of participants
RPA	31
PA in the macula	22
PA of the PR	22
PA in both the macula and PR	13
PA: location unspecified	2

Notes
[47] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with pigmentation of non-retinal ocular tissue (Non-ret. Pig. Abn)

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End point title

Percentage of participants with pigmentation of non-retinal ocular tissue (Non-ret. Pig. Abn)

End point description

Non-retinal ocular tissue abnormalities were determined by either an ophthalmologist or retina specialist. Non-ret. Pig. Abn is a composite endpoint assessed by its components: abnormal pigmentation (ABP) of the sclera and/or conjunctiva, ABP of the cornea, ABP of the iris and ABP of the lens. Only those participants with >=1 ophthalmology exam on or before last dose of retigabine are presented.

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	54 ^[48]
Units: Percentage of participants
Non-ret. Pig. Abn	28
ABP of sclera and/or conjunctiva	13
ABP of the cornea	4
ABP of the iris	17
ABP of the lens	0

Notes
[48] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with abnormal pigmentation of skin, including the skin around the eyes and the eyelids, lips, nails, or mucosa

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End point title

Percentage of participants with abnormal pigmentation of skin, including the skin around the eyes and the eyelids, lips, nails, or mucosa

End point description

Abnormal discoloration of the skin was determined by a dermatologist. The parameters assessed were abnormal discoloration of the skin, abnormal discoloration of the lips, abnormal discoloration of the nails, abnormal discoloration of the mucosa, abnormal discoloration of sun-exposed tissue, abnormal discoloration of non sun-exposed tissue. Only those participants with at least one skin exam by the investigator or dermatologist on or before the last dose of retigabine or dermatologist-confirmed discoloration with start date on or before the date of last dose of retigabine are presented.

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	46 ^[49]
Units: Percentage of participants
Any abnormal dermatologic discoloration	50
Abnormal discoloration of lips	26
Abnormal discoloration of skin	37
Abnormal discoloration of nails	41
Abnormal discoloration of mucosa	30
Abnormal discoloration of sun-exposed tissue	48
Abnormal discoloration of non sun-exposed tissue	37

Notes
[49] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with a clinically significant decrease (CSD) in visual acuity (VA) from initial examination

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End point title

Percentage of participants with a clinically significant decrease (CSD) in visual acuity (VA) from initial examination

End point description

VA refers to the clarity of vision. The parameters assessed were CSD in VA from initial examination which can be explained and CSD in VA from initial examination which cannot be explained. Only those participants with both initial and at least 1 follow-up exam while on retigabine are presented.

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	38 ^[50]
Units: Percentage of participants
CSD in VA from initial examination, n=38	13
CSD which can be explained (Form 2), n=34	12
CSD which can not be explained (Form 2), n=34	0

Notes
[50] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of participants with decrease in confrontation visual field from initial examination

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End point title

Percentage of participants with decrease in confrontation visual field from initial examination

End point description

The parameter assessed was decrease in confrontation visual field from initial examination. Only those participants with data available at the indicated time point were analyzed. Only those participants with both initial and at least 1 follow-up exam while on retigabine are presented.

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	38 ^[51]
Units: Percentage of participants
Percentage of participants	13

Notes
[51] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With Resolution of Abnormal Eye Pigmentation after Discontinuation of Retigabine

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End point title

Number of Participants With Resolution of Abnormal Eye Pigmentation after Discontinuation of Retigabine

End point description

The ophthalmologist/retina specialist determined the presence or absence of retinal and non-retinal ocular abnormalities. Retinal abnormalities included abnormalities in the macula and/or the peripheral retina. Only those participants available at the specified time points were analyzed. All SFUCP Subjects Population included participants with one or more finding(s) of abnormal pigmentation of the retina or unexplained vision loss, pigmentation of non-retinal ocular tissue or discoloration of skin, lips, nails or mucosa at the treatment phase withdrawal/follow-up visit and who enter the SFUCP phase.

End point type

Secondary

End point timeframe

3 years and 10 months

End point values	Safety follow-up continuation phase (SFUCP)
Number of subjects analysed	26 ^[52]
Units: Participants
Retinal pigmentary abnormality	0
Pigmentary abnormality of macula	1
Pigmentary abnormality of peripheral retina	2
Non-retinal ocular pigmentary abnormality	8

Notes
[52] - All SFUCP Subjects Population

No statistical analyses for this end point

Secondary: Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration after Discontinuation of Retigabine

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End point title

Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration after Discontinuation of Retigabine

End point description

An assessment of the participant’s nails, lips, skin and mucosa was completed by the investigator at the 6 monthly SFUCP study visits. The assessment of the participant’s skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa.

End point type

Secondary

End point timeframe

3 years and 10 months

End point values	Safety follow-up continuation phase (SFUCP)
Number of subjects analysed	26 ^[53]
Units: Participants	7

Notes
[53] - All SFUCP Subjects Population

No statistical analyses for this end point

Secondary: Time from Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

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End point title

Time from Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

End point description

Retinal pigmentary abnormality was determined by either an ophthalmologist or retina specialist. Retinal pigmentary abnormality included pigmentary abnormality of macula, pigmentary abnormality of the peripheral retina and non-retinal ocular pigmentary abnormality. If a participant had pigmentary abnormality of macula and pigmentary abnormality of the peripheral retina both should be resolved in order for retinal pigmentary abnormality to be considered resolved. If a participant had non-retinal ocular pigmentary abnormality in more than location (conjunctiva, sclera, cornea, iris or lens), all should be resolved for non-retinal pigmentary abnormality to be considered resolved. Only participants with resolution of the specified pigmentation are included in this analysis. 99999 indicates data was not available as no participants were analyzed.

End point type

Secondary

End point timeframe

3 years and 10 months

End point values	Safety follow-up continuation phase (SFUCP)
Number of subjects analysed	26 ^[54]
Units: Days
median (full range (min-max))
Retinal Pigmentary Abnormality, n=0	99999 (99999 to 99999)
Pigmentary Abnormality of Macula, n=1	233.0 (233 to 233)
Pigmentary Abnormality of Peripheral Retina, n=2	307.0 (245 to 369)
Non-Retinal Ocular Pigmentary Abnormality, n=8	312.0 (9 to 538)

Notes
[54] - All SFUCP Subjects Population

No statistical analyses for this end point

Secondary: Time from Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

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End point title

Time from Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

End point description

Assessments were at approximately 6-monthly intervals (timed relative to the participants previous dermatology assessment) until the abnormal discoloration either resolved or stabilized (as defined by no changes over 2 consecutive 6-monthly assessments performed by the dermatologist over at least 12 months after discontinuation of retigabine). The assessment of the participant’s skin included assessment of the skin around the eyes and the eyelids, lips, nails, and mucosa. Only participants with resolution of the specified tissue are included in this analysis.

End point type

Secondary

End point timeframe

3 years and 10 months

End point values	Safety follow-up continuation phase (SFUCP)
Number of subjects analysed	26 ^[55]
Units: Days
median (full range (min-max))
All, n=7	380.0 (197 to 672)
Skin, n=6	382.5 (162 to 425)
Lips, n=5	379.0 (197 to 672)
Nails,n=7	379.0 (197 to 462)
Mucosa, n=8	201.0 (175 to 425)

Notes
[55] - All SFUCP Subjects Population

No statistical analyses for this end point

Secondary: Percentage change in the 28-day partial seizure rate from the Baseline phase (obtained during the 8-week Baseline period of Study VRX-RET-E22-302) to open-label treatment.

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End point title

Percentage change in the 28-day partial seizure rate from the Baseline phase (obtained during the 8-week Baseline period of Study VRX-RET-E22-302) to open-label treatment.

End point description

28-day partial seizure rate observed during the OLE period was compared to the 28-day partial seizure rate observed during the Baseline phase of the double-blind parent study VRX-R ET-E22-302. Percent change from Baseline in 28-day total partial seizure rate was calculated as ([28-day partial seizure frequency for the period of interest – Baseline 28-day partial seizure frequency] / Baseline 28-day partial seizure frequency) × 100 percent. A negative percent change indicated a reduction (improvement) from Baseline, so the best possible outcome was -100 percent. Only those participants with data available at the indicated time point were analyzed.

End point type

Secondary

End point timeframe

Baseline and up to 121 months

End point values	Retigabine
Number of subjects analysed	371 ^[56]
Units: Percent change
arithmetic mean (standard deviation)
Percent change	-36.1 ± 95.77

Notes
[56] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of Participants with 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

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End point title

Percentage of Participants with 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

End point description

A Responder was defined as a participant with >=50 percent decrease from Baseline in the 28-day partial seizure frequency, i.e., a percent change from Baseline less than or equal to -50 percent. The percentage of responders from Baseline phase of the parent study (VRX-RET-E22-302) to open label treatment have been presented.

End point type

Secondary

End point timeframe

Baseline and up to 121 months

End point values	Retigabine
Number of subjects analysed	371 ^[57]
Units: Percentage of participants
Percentage of responders	52

Notes
[57] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants who were seizure free for any 6 continuous months

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End point title

Number of participants who were seizure free for any 6 continuous months

End point description

Seizure free for any continuous 6 months is defined as no seizures occuring during any consecutive 180 days between the first date (Baseline) and the last date (before tapering of dose). The number of participants who were seizure free for 6 continuous months within the 121 month OLE period have been presented.

End point type

Secondary

End point timeframe

Up to 6 continuous months within the 121 months period

End point values	Retigabine
Number of subjects analysed	279 ^[58]
Units: Participants
Participants	36

Notes
[58] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants who were seizure free for any 12 continuous months

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End point title

Number of participants who were seizure free for any 12 continuous months

End point description

Seizure free for any continuous 12 months is defined as no seizures occurring during any consecutive 360 days. Number of participants who were seizure free for 12 continuous months within the 121 month OLE period have been presented.

End point type

Secondary

End point timeframe

Up to 12 continuous months within the 121 months period

End point values	Retigabine
Number of subjects analysed	222 ^[59]
Units: Participants
Participants	22

Notes
[59] - Safety Population

No statistical analyses for this end point

Secondary: Percentage of seizure free days

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End point title

Percentage of seizure free days

End point description

A seizure free day is defined as the number of applicable days without any seizures (partial, generalized or unclassified). Only the days in which a subject had non-missing seizure data were considered as applicable days. Percentage of seizure free days is calculated as Number of seizure free days / number of applicable days × 100 percent. Only those participants with data available at the indicated time point were analyzed.

End point type

Secondary

End point timeframe

Up to 121 months

End point values	Retigabine
Number of subjects analysed	371 ^[60]
Units: Percentage of days
arithmetic mean (standard deviation)
Percentage of days	76.8 ± 26.11

Notes
[60] - Safety 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 adverse events (AEs) were collected from the start of the study treatment up to 122 months.

Adverse event reporting additional description

Safety population was used to assess AEs and SAEs.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Retigabine

Reporting group description

Eligible participants entered a 4-week transition phase of the double-blind parent study (study VRX-RET-E22-302), in which their dose of retigabine was titrated to or maintained at 300 mg three times daily (900 mg per day). Upon completion of the Transition phase of the parent study, participants enrolled into the extension study (RTG115097). Once enrolled in the OLE, doses were adjusted within the range of 600 mg to 1200 mg per day as an adjunct therapy to their ongoing AEDs with or without VNS up to 121 months.

Serious adverse events	Retigabine
Total subjects affected by serious adverse events
subjects affected / exposed	78 / 376 (20.74%)
number of deaths (all causes)	7
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Lymphoma
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Non-Hodgkin's lymphoma
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Plasma cell myeloma
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	1 / 1
Uterine leiomyoma
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Surgical and medical procedures
Tracheostomy
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Sudden unexplained death in epilepsy
subjects affected / exposed	3 / 376 (0.80%)
occurrences causally related to treatment / all	2 / 3
deaths causally related to treatment / all	2 / 3
Chest pain
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Social circumstances
Treatment noncompliance
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	2 / 376 (0.53%)
occurrences causally related to treatment / all	1 / 2
deaths causally related to treatment / all	0 / 0
Psychiatric disorders
Psychotic disorder
subjects affected / exposed	4 / 376 (1.06%)
occurrences causally related to treatment / all	2 / 4
deaths causally related to treatment / all	0 / 0
Confusional state
subjects affected / exposed	3 / 376 (0.80%)
occurrences causally related to treatment / all	3 / 3
deaths causally related to treatment / all	0 / 0
Psychogenic seizure
subjects affected / exposed	2 / 376 (0.53%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Aggression
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Agitation
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Anxiety
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Disorientation
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Epileptic psychosis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hallucination
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hallucination, auditory
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Hallucinations, mixed
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Obsessive-compulsive personality disorder
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Postictal psychosis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Suicidal ideation
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Suicide attempt
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Burns second degree
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Burns third degree
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Fall
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Femoral neck fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Foot fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Head injury
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hip fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Humerus fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Intentional overdose
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Jaw fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Near drowning
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Radius fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Rib fracture
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Road traffic accident
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Skull fractured base
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Nervous system disorders
Seizure
subjects affected / exposed	16 / 376 (4.26%)
occurrences causally related to treatment / all	6 / 23
deaths causally related to treatment / all	0 / 0
Epilepsy
subjects affected / exposed	6 / 376 (1.60%)
occurrences causally related to treatment / all	4 / 7
deaths causally related to treatment / all	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	5 / 376 (1.33%)
occurrences causally related to treatment / all	1 / 6
deaths causally related to treatment / all	0 / 0
Status epilepticus
subjects affected / exposed	5 / 376 (1.33%)
occurrences causally related to treatment / all	1 / 6
deaths causally related to treatment / all	0 / 0
Dizziness
subjects affected / exposed	3 / 376 (0.80%)
occurrences causally related to treatment / all	2 / 3
deaths causally related to treatment / all	0 / 0
Focal dyscognitive seizures
subjects affected / exposed	3 / 376 (0.80%)
occurrences causally related to treatment / all	0 / 3
deaths causally related to treatment / all	0 / 0
Coma
subjects affected / exposed	2 / 376 (0.53%)
occurrences causally related to treatment / all	1 / 2
deaths causally related to treatment / all	0 / 0
Arachnoid cyst
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ataxia
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Depressed level of consciousness
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Dysarthria
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Facial paralysis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Incoherent
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Partial seizures
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Partial seizures with secondary generalisation
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Seizure cluster
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 2
deaths causally related to treatment / all	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Eye disorders
Retinal pigmentation
subjects affected / exposed	3 / 376 (0.80%)
occurrences causally related to treatment / all	3 / 3
deaths causally related to treatment / all	0 / 0
Diplopia
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Vision blurred
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Acute abdomen
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Nausea
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vomiting
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cholelithiasis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Drug-induced liver injury
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Skin and subcutaneous tissue disorders
Pigmentation disorder
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Renal and urinary disorders
Hydronephrosis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Nephropathy toxic
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Pain in extremity
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Bronchitis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cellulitis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	1 / 1
Gastroenteritis
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pneumonia
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Pneumonia streptococcal
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Septic shock
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	1 / 1
Typhoid fever
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	2 / 376 (0.53%)
occurrences causally related to treatment / all	1 / 2
deaths causally related to treatment / all	0 / 0

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

Non-serious adverse events	Retigabine
Total subjects affected by non serious adverse events
subjects affected / exposed	239 / 376 (63.56%)
Nervous system disorders
Dizziness
subjects affected / exposed	83 / 376 (22.07%)
occurrences all number	140
Somnolence
subjects affected / exposed	78 / 376 (20.74%)
occurrences all number	99
Headache
subjects affected / exposed	61 / 376 (16.22%)
occurrences all number	231
Tremor
subjects affected / exposed	34 / 376 (9.04%)
occurrences all number	42
Memory impairment
subjects affected / exposed	26 / 376 (6.91%)
occurrences all number	31
Seizure
subjects affected / exposed	22 / 376 (5.85%)
occurrences all number	37
Aphasia
subjects affected / exposed	20 / 376 (5.32%)
occurrences all number	27
Amnesia
subjects affected / exposed	19 / 376 (5.05%)
occurrences all number	23
General disorders and administration site conditions
Fatigue
subjects affected / exposed	43 / 376 (11.44%)
occurrences all number	50
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	19 / 376 (5.05%)
occurrences all number	19
Gastrointestinal disorders
Oral mucosal discolouration
subjects affected / exposed	20 / 376 (5.32%)
occurrences all number	23
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	22 / 376 (5.85%)
occurrences all number	25
Infections and infestations
Viral upper respirator tract infection
subjects affected / exposed	30 / 376 (7.98%)
occurrences all number	45
Influenza
subjects affected / exposed	24 / 376 (6.38%)
occurrences all number	42
Urinary tract infection
subjects affected / exposed	21 / 376 (5.59%)
occurrences all number	25

More information

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Were there any global substantial amendments to the protocol? Yes

02 Jul 2007

• A urine pregnancy test at Visit 0, for female participants, was added. • Pregnancy exclusion criteria were more clearly defined. • Modifications of dosage scheduling were allowed and defined for the investigator. • Interim study visits were added to allow more frequent haematological monitoring per Food and Drug Administration (FDA) comment. • Expedited reporting of low neutrophil counts and discontinuation due to haematological reasons or infections was added per FDA comment.

14 Aug 2008

• Extended the study from 36 to 48 months • American Urological Association (AUA) and post-void residual (PVR) assessments added at the end of second, third and fourth year of this study at Visits 8, 11 and 14. • Full physical and neurological examination to be performed at Visit 14 and brief neurological examinations added at Visits 12 and 13. • Added a 12-lead ECG at Visit 14. • Participants tapering/discontinuing in the fourth year, were to complete assessments and evaluations scheduled for Visit 14.

10 Mar 2010

• Visits X, Y, Z were added to enable an open ended visit schedule. Study Visit_X, Study Visit_Y and Study Visit _Z/Early Termination occurred in 4 month intervals and designated additional 12-month periods after the participanthad completed Visit 14 in the study. Once the participant had completed Study V_Z/Early Termination, they repeated Study V_X at the next scheduled visit and entered into the subsequent 12 month cycle. This continued for each 12-month period, providing an open-ended visit schedule, which allowed participant to remain on treatment until the study drug, retigabine, was approved and commercially available, or until the program was discontinued. • Information on when participant were to return for the final visit after discontinuation was clarified as 1 to 30 days following their last dose intake of study drug.

08 Mar 2011

• Ownership of retigabine and sponsorship of the study were transferred from Valeant Pharmaceuticals International, Inc to GSK • From this amendment, retigabine was supplied by GSK.

03 Nov 2011

• Updated Quintiles address • Clarified there was to be a 3-week tapering period for participant who withdrew from the study prematurely • Clarified that the 30-day post-study period for collection of AEs was for all subjects • Added participant switched to commercially available retigabine as a reason for withdrawal and included information on how to switch participant to commercially available retigabine.

11 Dec 2012

• Included the option to continue retigabine in another long-term study if this study was discontinued by the Sponsor if the subject was expected to benefit from continued treatment. • All participant were referred to an ophthalmologist for baseline eye examinations and annual eye examinations included in the study procedures. • If a participant withdrew from the study early, an eye examination was to be performed if it had been greater than 6 months since their last examination. • Any participant with discolouration/pigmentation of nail, skin and/or mucosal surfaces were referred to a dermatologist who completed the Targeted Follow-up Questionnaire.

06 Nov 2013

• Included an additional secondary objective to evaluate whether retinal pigmentation, unexplained vision loss, pigmentation of non-retinal ocular tissue (NROT) and discolouration of nails (DON), lips, skin or mucosa change over time after discontinuation of retigabine. • Removed the option to continue retigabine in another long-term open-label safety study; requirement to transition participants to commercial retigabine when available was removed (made optional). • The study design was modified to include a SFUCP for eligible participants. • Added the new assessments (comprehensive eye and dermatological examination) and 2 analysis phases (primary and final completion) to allow for reporting after the end of the Open-Label/Safety Follow-up Phase and after the end of the overall study. • Follow-up comprehensive skin and eye examinations were collected for participants who previously discontinued retigabine. • Details on procedures to be carried out during the SFUCP were added. • Additional reasons for withdrawal from the Open-Label Treatment Phase/ study were added which included occurrence of any of the following events: agranulocytosis, anaphylaxis and anaphylactoid reactions, hepatotoxicity, acute renal failure, Stevens Johnson Syndrome/Toxic Epidermal Necrolysis, actual/risk of suicide attempt, status epilepticus in a participant who does not have a history of previous episodes of status epilepticus/risk of retinal pigmentation and possible associated vision loss that outweighs the benefits of continued treatment with retigabine for participants who have other suitable treatment options. • The following were designated adverse events of special interest (AESIs): RPA and/or vision loss (e.g., decrease in visual acuity and/visual field), pigmentation of NROT (conjunctiva, sclera, iris) DON, lips, skin, and mucosa. • Added Appendix E for the plan to collect an optional blood sample for potential pharmacogenetic (PGx) analysis in participants on treatment/SFUCP.

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: A multicenter, open-label, long-term, safety, tolerability and efficacy study of retigabine in adult epilepsy patients with partial-onset seizures (Extension of Study VRX-RET-E22-302)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with treatment emergent adverse events (TEAEs) and Serious adverse events (TESAEs)

Primary: Number of participants with treatment emergent adverse events (TEAEs) and Serious adverse events (TESAEs)

Primary: Number of participants with TEAEs leading to treatment discontinuation (disc.)

Primary: Number of participants with TEAEs leading to treatment discontinuation (disc.)

Primary: Kaplan-Meier estimate of the Probability of disc. from Study Drug

Primary: Kaplan-Meier estimate of the Probability of disc. from Study Drug

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in the supine and standing position

Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in the supine and standing position

Primary: Change from Baseline in heart rate (HR) measurements in the supine and standing position

Primary: Change from Baseline in heart rate (HR) measurements in the supine and standing position

Primary: Change from Baseline in body temperature

Primary: Change from Baseline in body temperature

Primary: Change from Baseline in body weight

Primary: Change from Baseline in body weight

Primary: Change from Baseline in Electocardiogram (ECG) parameters PR, QRS, QT, corrected QT interval (QTc) Bazett and QTc Friedericia

Primary: Change from Baseline in Electocardiogram (ECG) parameters PR, QRS, QT, corrected QT interval (QTc) Bazett and QTc Friedericia

Primary: Change from Baseline in alkaline phosphatase (Alk. Phos.), alanine amino transferase (ALT) and aspartate amino transferase (AST)

Primary: Change from Baseline in alkaline phosphatase (Alk. Phos.), alanine amino transferase (ALT) and aspartate amino transferase (AST)

Primary: Change from Baseline in bicarbonate, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium and urea

Primary: Change from Baseline in bicarbonate, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium and urea

Primary: Change from Baseline in creatinine, total bilirubin and uric acid

Primary: Change from Baseline in creatinine, total bilirubin and uric acid

Primary: Change from Baseline in total protein

Primary: Change from Baseline in total protein

Primary: Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, white blood cells (WBC)

Primary: Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet count, white blood cells (WBC)

Primary: Change from Baseline in hematocrit

Primary: Change from Baseline in hematocrit

Primary: Change from Baseline in hemoglobin

Primary: Change from Baseline in hemoglobin

Primary: Change from Baseline in hematology parameter red blood cells (RBC)

Primary: Change from Baseline in hematology parameter red blood cells (RBC)

Primary: Change from Baseline in urine specific gravity

Primary: Change from Baseline in urine specific gravity

Primary: Change from Baseline in urine potential of hydrogen (pH)

Primary: Change from Baseline in urine potential of hydrogen (pH)

Primary: Change from Baseline in Post-Void Residual (PVR) bladder ultrasound volume

Primary: Change from Baseline in Post-Void Residual (PVR) bladder ultrasound volume

Primary: Change from Baseline in the urinary voiding function [UVF] (assessed using the American Urological Association [AUA] Symptom Index)

Primary: Change from Baseline in the urinary voiding function [UVF] (assessed using the American Urological Association [AUA] Symptom Index)

Primary: Change from Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire

Primary: Change from Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire

Primary: Percentage of participants with Abnormal Results of Physical Examination

Primary: Percentage of participants with Abnormal Results of Physical Examination

Primary: Percentage of participants with Abnormal Results of Neurological Examination

Primary: Percentage of participants with Abnormal Results of Neurological Examination

Secondary: Percentage of participants with retinal pigmentary abnormalities (RPA)

Secondary: Percentage of participants with retinal pigmentary abnormalities (RPA)

Secondary: Percentage of participants with pigmentation of non-retinal ocular tissue (Non-ret. Pig. Abn)

Secondary: Percentage of participants with pigmentation of non-retinal ocular tissue (Non-ret. Pig. Abn)

Secondary: Percentage of participants with abnormal pigmentation of skin, including the skin around the eyes and the eyelids, lips, nails, or mucosa

Secondary: Percentage of participants with abnormal pigmentation of skin, including the skin around the eyes and the eyelids, lips, nails, or mucosa

Secondary: Percentage of participants with a clinically significant decrease (CSD) in visual acuity (VA) from initial examination

Secondary: Percentage of participants with a clinically significant decrease (CSD) in visual acuity (VA) from initial examination

Secondary: Percentage of participants with decrease in confrontation visual field from initial examination

Secondary: Percentage of participants with decrease in confrontation visual field from initial examination

Secondary: Number of Participants With Resolution of Abnormal Eye Pigmentation after Discontinuation of Retigabine

Secondary: Number of Participants With Resolution of Abnormal Eye Pigmentation after Discontinuation of Retigabine

Secondary: Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration after Discontinuation of Retigabine

Secondary: Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration after Discontinuation of Retigabine

Secondary: Time from Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

Secondary: Time from Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation

Secondary: Time from Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

Secondary: Time from Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration

Secondary: Percentage change in the 28-day partial seizure rate from the Baseline phase (obtained during the 8-week Baseline period of Study VRX-RET-E22-302) to open-label treatment.

Secondary: Percentage change in the 28-day partial seizure rate from the Baseline phase (obtained during the 8-week Baseline period of Study VRX-RET-E22-302) to open-label treatment.

Secondary: Percentage of Participants with 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

Secondary: Percentage of Participants with 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment

Secondary: Number of participants who were seizure free for any 6 continuous months

Secondary: Number of participants who were seizure free for any 6 continuous months

Clinical Trial Results:
A multicenter, open-label, long-term, safety, tolerability and efficacy study of retigabine in adult epilepsy patients with partial-onset seizures (Extension of Study VRX-RET-E22-302)