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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

Results information
Results version number	v2
This version publication date	19 May 2018
First version publication date	08 Apr 2018
Other versions	v1 , v3 , v4
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

Interim

Date of interim/final analysis

25 Sep 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Apr 2017

Global end of trial reached?

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

11 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) entered this open label extension (OLE) study. The results presented are based on the analysis of data of primary reporting phase.

Period 1 title

Overall Study (overall period)

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

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

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

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End point title

Number of participants with TEAEs leading to treatment discontinuation ^[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 discontinuation 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 Discontinuation from Study Drug

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End point title

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

End point description

Kaplan-Meier estimate of the probability of discontinuation at the specified time for all participants is presented. The time frame of premature study discontinuation 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 of participants
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 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
[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 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
[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 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
[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 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
[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 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
[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 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
[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

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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 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
[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 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
[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 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
[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. NA 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
[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 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
[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)

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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 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
[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 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
[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 that 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
[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 that 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
[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 by the Investigator 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 in the Open-Label Treatment Phase ( second year, third year, fourth year) to assess the participant UVF. The questions were scored on a scale of 0 to 5, with 0 being (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 data was not available. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category tittles

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 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 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
[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 confrontational visual field from initial examination

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End point title

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

End point description

The parameter assessed was decrease in confrontational 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: 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 ^[52]
Units: Percent change
arithmetic mean (standard deviation)
Percent change	-36.1 ( 95.77 )

Notes
[52] - 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 ^[53]
Units: Percentage of participants
Percentage of responders	52

Notes
[53] - 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 ^[54]
Units: Participants
Participants	36

Notes
[54] - 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 ^[55]
Units: Participants
Participants	22

Notes
[55] - 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 ^[56]
Units: Percentage of days
arithmetic mean (standard deviation)
Percentage of days	76.8 ( 26.11 )

Notes
[56] - 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 upto 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
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
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
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
Ataxia
subjects affected / exposed	1 / 376 (0.27%)
occurrences causally related to treatment / all	1 / 1
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
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

Top of page

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

Primary: Number of participants with TEAEs leading to treatment discontinuation

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

Primary: Kaplan-Meier estimate of the Probability of Discontinuation 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 confrontational visual field from initial examination

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

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

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

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

Secondary: Percentage of seizure free days

Secondary: Percentage of seizure free days

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

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)