carbamates and Liver Diseases studies

Research Excerpts

Excerpt	Relevance	Reference
"Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection."	3.83	Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. ( Bahirwani, R; Berg, C; Brown, RS; Castells, L; Chacko, KR; Durand, CM; ElSharkawy, AM; Emond, B; Ferenci, P; Fontana, RJ; Herzer, K; Ionescu-Ittu, R; Jafri, SM; Joshi, S; Knop, V; Lionetti, R; Loiacono, L; Londoño, MC; Montalbano, M; Moreno-Zamora, A; Mubarak, A; Pellicelli, AM; Prieto, M; Reddy, KR; Stadler, B; Stauber, RE; Stenmark, S; Torti, C; Vekeman, F; Weiland, O, 2016)
" For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily delivered 17% higher values for the maximum plasma amprenavir concentration at the steady state (C(max)), 22% higher values for the area under the plasma concentration versus time curve over the dosing interval at the steady state [AUC(0-tau)], similar values for the concentration at the end of the dosing interval (C(tau)), and 114% higher unbound C(tau) values."	2.74	Pharmacokinetics of fosamprenavir plus ritonavir in human immunodeficiency virus type 1-infected adult subjects with hepatic impairment. ( Clotet, B; Felizarta, F; Gutiérrez, F; Hernández-Quero, J; Lou, Y; Morellon, ML; Nichols, G; Ortega, E; Pérez-Elías, MJ; Pineda, JA; Rodríguez-Torres, M; Wire, MB, 2009)
"Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus."	2.69	Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. ( Christensen, MS; Hatorp, V; Haug-Pihale, G; Walther, KH, 2000)
" Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers."	2.69	Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function. ( Delvaux, M; Fosse, S; Gillotin, C; Lou, Y; Masliah, C; Petite, JP; Pillegand, B; Rautaureau, J; Sadler, BM; Stein, DS; Veronese, L, 2000)
"This manuscript summarizes the pharmacokinetic and biopharmaceutical properties of retigabine collated from published and unpublished in vitro and clinical phase I-III studies in healthy volunteers or patients with partial-onset seizures."	2.49	Clinical pharmacokinetics of retigabine/ezogabine. ( Crean, CS; Tompson, DJ, 2013)
"Repaglinide is a novel, fast-acting prandial oral hypoglycaemic agent developed for the treatment of patients with type 2 diabetes whose disease cannot be controlled by diet and exercise alone."	2.41	Clinical pharmacokinetics and pharmacodynamics of repaglinide. ( Hatorp, V, 2002)
"Participants with mild, moderate, or severe hepatic impairment and age-, sex-, and weight-matched healthy controls were enrolled in a 3-part, open-label, sequential-panel, single-dose pharmacokinetic study."	1.48	Pharmacokinetics, Safety, and Tolerability of Single-Dose Elbasvir in Participants with Hepatic Impairment. ( Butterton, JR; Caro, L; Fandozzi, C; Feng, HP; Garrett, G; Huang, X; Iwamoto, M; Lasseter, KC; Liu, F; Marbury, T; Marshall, WL; Panebianco, D; Preston, RA; Wenning, L; Yeh, WW, 2018)
"Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs."	1.31	Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat. ( Akbarsha, MA; Faridha, A; Girija, R; Kadalmani, B; Vijendrakumar, S, 2000)
" To study the mechanism of this toxicity, suspensions of mouse hepatocytes were tested as an in vitro model system suitable for the study of the relationship between (i) the toxic potential of formamides, (ii) their metabolism to N-alkylcarbamoylating species, and (iii) their ability to deplete hepatic glutathione pools."	1.27	Cytotoxicity and metabolism of the hepatotoxin N-methylformamide and related formamides in mouse hepatocytes. ( Gescher, A; Mráz, J; Shaw, AJ, 1988)

Research

Studies (15)

Authors

Clinical Trials (4)

Trial Overview

Trial Outcomes

Apparent Terminal Half-Life (t1/2) of Elbasvir

Timeframe	Studies, this research(%)	All Research%
pre-1990	5 (33.33)	18.7374
1990's	0 (0.00)	18.2507
2000's	6 (40.00)	29.6817
2010's	4 (26.67)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Marshall, WL	1
Feng, HP	1
Wenning, L	1
Garrett, G	1
Huang, X	1
Liu, F	1
Panebianco, D	1
Caro, L	1
Fandozzi, C	1
Lasseter, KC	1
Preston, RA	1
Marbury, T	1
Butterton, JR	1
Iwamoto, M	1
Yeh, WW	1
Fontana, RJ	1
Brown, RS	1
Moreno-Zamora, A	1
Prieto, M	1
Joshi, S	1
Londoño, MC	1
Herzer, K	1
Chacko, KR	1
Stauber, RE	1
Knop, V	1
Jafri, SM	1
Castells, L	1
Ferenci, P	1
Torti, C	1
Durand, CM	1
Loiacono, L	1
Lionetti, R	1
Bahirwani, R	1
Weiland, O	1
Mubarak, A	1
ElSharkawy, AM	1
Stadler, B	1
Montalbano, M	1
Berg, C	1
Pellicelli, AM	1
Stenmark, S	1
Vekeman, F	1
Ionescu-Ittu, R	1
Emond, B	1
Reddy, KR	1
Rockstroh, JK	1
Ingiliz, P	1
Petersen, J	1
Peck-Radosavljevic, M	1
Welzel, TM	1
Van der Valk, M	1
Zhao, Y	1
Jimenez-Exposito, MJ	1
Zeuzem, S	1
Pérez-Elías, MJ	1
Morellon, ML	1
Ortega, E	1
Hernández-Quero, J	1
Rodríguez-Torres, M	1
Clotet, B	1
Felizarta, F	1
Gutiérrez, F	1
Pineda, JA	1
Nichols, G	1
Lou, Y	2
Wire, MB	1
Tompson, DJ	1
Crean, CS	1
Seminari, E	1
De Bona, A	1
Gentilini, G	1
Galli, L	1
Schira, G	1
Gianotti, N	1
Uberti-Foppa, C	1
Soldarini, A	1
Dorigatti, F	1
Lazzarin, A	1
Castagna, A	1
Hatorp, V	2
Walther, KH	1
Christensen, MS	1
Haug-Pihale, G	1
Veronese, L	1
Rautaureau, J	1
Sadler, BM	1
Gillotin, C	1
Petite, JP	1
Pillegand, B	1
Delvaux, M	1
Masliah, C	1
Fosse, S	1
Stein, DS	1
Akbarsha, MA	1
Vijendrakumar, S	1
Kadalmani, B	1
Girija, R	1
Faridha, A	1
Enat, R	1
Barzilai, D	1
Gellei, B	1
Shaw, AJ	1
Gescher, A	1
Mráz, J	1
Yamazaki, H	1
Sano, T	1
Odakura, T	1
Takeuchi, K	1
Matsumura, T	1
Hosaki, S	1
Shimamoto, T	1
Seawright, AA	2
Mattocks, AR	2

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Three-Part, Open-Label, Single-Dose Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of MK-8742[NCT01797536]	Phase 1	31 participants (Actual)	Interventional	2013-03-06	Completed
Efficacy and Safety of Sofosbuvir/Simeprevir Plus a Flat Dose of Ribavirin in Genotype 1 Elderly Cirrhotic Patients: a Real Life Study[NCT02702739]	Phase 4	270 participants (Actual)	Interventional	2015-01-31	Completed
A Multicenter Compassionate Use Program of Daclatasvir (BMS-790052) in Combination With Sofosbuvir With or Without Ribavirin for the Treatment of Subjects With Chronic Hepatitis C[NCT02097966]		0 participants	Expanded Access		No longer available
Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study - Determine Efficacy and Safety of Two Doses of Retigabine (900 Mg/Day and 600 Mg/Day) Used as Adjunctive Therapy in Refractory Epilepsy Patients With Partial-Onset Se[NCT00235755]	Phase 3	539 participants (Actual)	Interventional	2005-12-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the t1/2 of elbasvir. (NCT01797536)
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir

Intervention	hr (Geometric Mean)
Mild Hepatic Insufficiency	24.80
Moderate Hepatic Insufficiency	25.39
Severe Hepatic Insufficiency	33.72
Healthy Participants	20.74

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 to determine the AUC0-24hr of elbasvir. (NCT01797536)
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24

Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir

Intervention	μM•hr (Geometric Mean)
Mild Hepatic Insufficiency	0.87
Moderate Hepatic Insufficiency	0.92
Severe Hepatic Insufficiency	0.92
Healthy Participants	1.45

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the AUC0-inf of elbasvir. (NCT01797536)
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168

Concentration at 24 Hours (C24) After Dosing Elbasvir

Intervention	μM•hr (Geometric Mean)
Mild Hepatic Insufficiency	1.56
Moderate Hepatic Insufficiency	1.86
Severe Hepatic Insufficiency	2.28
Healthy Participants	2.58

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24, to determine the concentration of elbasvir at Hour 24 was determined. (NCT01797536)
Timeframe: Hour 24

Maximum Concentration (Cmax) of Elbasvir

Intervention	nM (Geometric Mean)
Mild Hepatic Insufficiency	22.9
Moderate Hepatic Insufficiency	25.9
Severe Hepatic Insufficiency	29.6
Healthy Participants	37.7

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the Cmax of Elbasvir. (NCT01797536)
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Time to Maximum Concentration (Tmax) of Elbasvir

Intervention	nM (Geometric Mean)
Mild Hepatic Insufficiency	70.1
Moderate Hepatic Insufficiency	83.0
Severe Hepatic Insufficiency	70.7
Healthy Participants	121.0

Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the maximum concentration (Cmax) of elbasvir. The time to reach Cmax (Tmax) was determined. (NCT01797536)
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168

Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase

Intervention	hour (hr) (Median)
Mild Hepatic Insufficiency	3.50
Moderate Hepatic Insufficiency	3.50
Severe Hepatic Insufficiency	4.00
Healthy Participants	3.50

Clinical Global Impression of Improvement (CGI-I) is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the treatment. Scores on the scale are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. (NCT00235755)
Timeframe: Week 16/end of treatment phase

Patient Global Impression (PGI) Score at the End of the Maintenance Phase

Intervention	scores on a scale (Mean)
Placebo - DB Phase (Titration Plus Maintenance)	3.2
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	2.9
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	2.9

PGI is a participant-rated scale of improvement that was administered at the end of the Maintenance Phase in order to assess the participant's impression of his or her own improvement. PGI assessments were scored using a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. (NCT00235755)
Timeframe: Week 16/end of treatment phase

Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

Intervention	scores on a scale (Mean)
Placebo - DB Phase (Titration Plus Maintenance)	3.3
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	2.9
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	3.0

28-day total partial seizure frequency in the BL period = (No. of total partial seizures reported in the BL period divided by the No. of days of available total partial seizure data in the BL period) x 28 days. 28-day total partial seizure frequency in the Maintenance Phase = (No. of total partial seizures reported in the Maintenance Phase divided by the No. of days of available total partial seizure data in the same phase) x 28 days. Percent change = (value in the Maintenance Phase minus value at BL divided by the BL value) x 100%. Negative values indicate a reduction in seizure frequency. (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16

Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)

Intervention	Percent change in seizure frequency (Median)
Placebo - DB Phase (Titration Plus Maintenance)	-17.4
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	-35.3
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	-44.3

28-day total PS (PSs [also called focal seizures] are seizures limited to a specific area of the brain) frequency in the BL period = (Number [No.] of total PSs reported in the BL period divided by the No. of days of available total PS data in the BL period) x 28 days. 28-day total PS frequency in the DB period = (No. of total PSs reported in the DB period divided by the No. of days of available total PS data in the DB period) x 28 days. Percent change = ([value in the DB period minus value at BL] divided by the BL value) x 100%. Negative valu es indicate a reduction in seizure frequency. (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)

Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)

Intervention	percent change in seizure frequency (Median)
Placebo - Double Blind (DB) Phase (Titration Plus Maintenance)	-15.9
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	-39.9
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	-27.9

A seizure-free day was a day without any seizures. For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. The percentage of seizure-free days was calculated as the total number of days without seizures in the DB period divided by the number of days in DB period x 100%. (NCT00235755)
Timeframe: Week 1 through Week 16

Percentage of Seizure-free Days During the Maintenance Phase

Intervention	percentage of days (Median)
Placebo - DB Phase (Titration Plus Maintenance)	77.8
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	79.5
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	82.1

A seizure-free day was a day without any seizures. The percentage of seizure-free days was calculated as the total number of days without seizures in the Maintenance Phase divided by the number of days in the Maintenance Phase x 100%. (NCT00235755)
Timeframe: Week 5 through Week 16

Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase

Intervention	percentage of days (Median)
Placebo - DB Phase (Titration Plus Maintenance)	78.1
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	81.6
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	84.5

Post-void residual (PVR) urine refers to the amount of urine remaining in the bladder after normal urination. To investigate the possible effects of retigabine on bladder function, all participants underwent post-void residual bladder ultrasound at Baseline and during the Maintenance Phase. The PVR bladder ultrasound was performed by a urologist, a qualified ultrasound technician, or a qualified study nurse who was certified to do PVR bladder ultrasound. Change from Baseline in PVR residual volume was calculated as the values at Week 10 and Week 16 minus the value at Baseline. (NCT00235755)
Timeframe: Baseline (Week -7 through 0), Weeks 8 and 16

Number of Participants Classified as Responders and Non-responders During the Maintenance Phase

Intervention	milliliters (Median)
	Week 8, n=143, 134, 121	Week 16, n=141, 131, 115
Placebo: Maintenance Phase	0	0
Retigabine 200 mg TID: Maintenance Phase	0	0
Retigabine 300 mg TID: Maintenance Phase	0	0

Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the Maintenance Phase as compared to the Baseline period. (NCT00235755)
Timeframe: Week 5 through Week 16

Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline

Intervention	participants (Number)
	Responders	Non-responders
Placebo - DB Phase (Titration Plus Maintenance)	31	133
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance	61	97
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	70	79

New seizure types included those seizures which were not reported by any participant at Baseline. (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16

Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase

Intervention	participants (Number)
	Partial seizures without motor signs	Partial evolving to secondarily generalized	Partial seizures with motor signs	Tonic-clonic seizures	Flurries	Tonic seizures	Complex partial seizures	Unclassified seizures
Placebo - DB Phase (Titration Plus Maintenance)	9	6	5	0	3	3	1	0
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	8	5	6	0	2	0	4	1
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	12	9	3	3	1	1	4	0

Participants who experienced an exacerbation from Baseline in the 28-day total partial seizure frequency were categorized as having a 0-25% or a >25% increase (EMEA endpoint). The number of participants experiencing a >0% reduction from Baseline in the 28-day total partial seizure frequency are also presented. (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16

Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)

Intervention	participants (Number)
	0% to 25% increase	>=25% increase	>0% reduction
Placebo - DB Phase (Titration Plus Maintenance)	28	22	114
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	14	23	121
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	11	19	119

A summary of the adverse events classified as renal or urinary disorders and in which at least 2% (rounded to an integer) of participants in any treatment arm reported during the study is presented. (NCT00235755)
Timeframe: Week 1 through Week 16

Number of Participants Who Were Responders and Non-responders During the DB Phase

Intervention	participants (Number)
	Dysuria	Urinary retention	Polyuria	Urinary hesitation	Haematuria
Placebo - DB Phase (Titration Plus Maintenance)	0	0	4	3	2
Placebo - Transition Phase	0	0	0	3	1
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	3	1	1	6	5
Retigabine 200 mg TID - Transition Phase	0	0	0	1	0
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	4	4	2	1	2
Retigabine 300 mg TID - Transition Phase	0	0	0	0	1

Responders were participants with at least a 50% reduction in the 28-day total partial seizure frequency in the DB Phase as compared to the Baseline period. Participants without any post-baseline data were considered non-responders. (NCT00235755)
Timeframe: Week 1 through Week 16

Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)

Intervention	participants (Number)
	Responders	Non-responders
Placebo - DB Phase (Titration Plus Maintenance)	31	148
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	57	124
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	70	108

Participants were considered to be seizure-free if they had not reported any seizures during the DB treatment period (Weeks 1-18). For a participant to be seizure free during the DB Phase, the participant had to be seizure free both Week 7 to Week 18 and Week 1 to Week 6. A participant could be seizure free Week 7 to Week 18 (during the Maintenance Phase), but not seizure free Week 1 to Week 6. Hence, there are fewer participants being reported as seizure free from Week 1 to Week 18 than from Week 7 to Week 18. (NCT00235755)
Timeframe: Week 1 through Week 16

Number of Participants Who Were Seizure-free During the Maintenance Phase

Intervention	participants (Number)
	Seizure-free	Not seizure-free
Placebo - DB Phase (Titration Plus Maintenance)	2	174
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	0	179
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	7	168

Participants were considered to be seizure-free if they had not reported any seizures during the Maintenance Phase. (NCT00235755)
Timeframe: Week 5 through Week 16

Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)

Intervention	participants (Number)
	Seizure-free	Not seizure-free
Placebo - DB Phase (Titration Plus Maintenance)	2	162
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	5	153
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	7	142

Clinically important changes in laboratory values were to be reported as an adverse event if they met one of the following criteria: (1) intervention required; (2) change in dose of study drug required; (3) other treatment/therapy required; (4) association with other diagnoses. (NCT00235755)
Timeframe: Week 1 through Week 16

Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase

Intervention	participants (Number)
	Protenuria	Hyperlipidemia	Hypercholesterolemia	Hematuria
Placebo - DB Phase (Titration Plus Maintenance)	3	3	2	2
Placebo - Transition Phase	0	0	0	1
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	2	0	4	5
Retigabine 200 mg TID - Transition Phase	1	0	0	0
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	0	0	1	2
Retigabine 300 mg TID - Transition Phase	0	0	1	1

The number of participants with recorded weight gain of >=7% over their baseline weight was measured. (NCT00235755)
Timeframe: Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase

Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories

Intervention	participants (Number)
	Week 2, n=174, 180, 175	Week 4, n=169, 172, 167	Week 6, n=169, 165, 152	Week 8, n=161, 160, 149	Week 12, n=159, 151, 144	Week 16, n=153, 139, 132
Placebo - DB Phase (Titration Plus Maintenance)	0	0	1	1	6	4
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	3	7	8	9	15	13
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	3	8	7	7	13	12

Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized in decile cutting, i.e., reduction categories of 90-100%, 80-<90%, 70-<80%, 60-<70%, 50-<60%, 40-<50%, 30-<40%, 20-<30%, 10-<20%, >0-<10%, and increase categories of 0-10%, >10-20%, >20-30%, >30% (FDA endpoint). Participants without any post-baseline data were included in the category 0-10% increase category. (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16

Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories

Intervention	participants (Number)
	Reduction: 90% to 100%	Reduction: 80% to <90%	Reduction: 70% to <80%	Reduction: 60% to <70%	Reduction: 50% to <60%	Reduction: 40% to <50%	Reduction: 30% to <40%	Reduction: 20% to <30%	Reduction: 10% to <20%	Reduction: >0% to <10%	Increase: 0% to 10%	Increase: >10% to 20%	Increase: >20% to 30%	Increase: >30%
Placebo - DB Phase (Titration Plus Maintenance)	3	4	8	7	9	9	15	24	18	16	20	13	8	25
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	5	8	11	14	19	13	16	16	18	13	11	9	3	25
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	11	14	7	21	17	17	21	9	10	8	11	7	1	24

"Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a reduction of 75-100%, 50-<75%, 25-<50%, or <25%, in addition to having no reduction. This quartile cutting was specified in the study protocol. Participants without any post-baseline data are included in the No reduction category." (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 1 through Week 16

Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase

Intervention	participants (Number)
	75% to 100% reduction	50% to <75% reduction	25% to <50% reduction	>0 to <25% reduction	No reduction
Placebo - DB Phase (Titration Plus Maintenance)	12	19	39	43	66
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	16	41	38	38	48
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	27	43	41	24	43

Participants who experienced a reduction from Baseline in the 28-day total partial seizure frequency were categorized as having a >75%, a 50-75%, or a <50% reduction, in addition to having no reduction (EMEA endpoint). (NCT00235755)
Timeframe: Baseline (Week -7 through Week 0), Week 5 through Week 16

Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16

Intervention	participants (Number)
	>75% reduction	50% to 75% reduction	>0 to <50% reduction	No reduction
Placebo - DB Phase (Titration Plus Maintenance)	11	20	83	50
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	27	34	60	37
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	30	40	49	30

The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry, emotional well being, energy/fatigue, cognitive functioning, medication effects, social functioning, overall QOL. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are first converted to 0-100 point scores; higher converted scores always reflect better QOL. The overall score is derived by weighting and then summing the 7 domain scores. (NCT00235755)
Timeframe: End of Baseline (Week 0), Weeks 4, 8, and 16

Intervention	scores on a scale (Mean)
	Baseline, n=165, 173, 166	Week 4 (Titration Phase), n=155, 155, 149)	Week 8 (Maintenance Phase), n=141, 146, 127	Week 16 (Maintenance Phase), n=143, 133, 123
Placebo - DB Phase (Titration Plus Maintenance)	53.3	55.4	55.3	54.7
Retigabine 200 mg TID - DB Phase (Titration Plus Maintenance)	56.0	57.3	59.6	59.1
Retigabine 300 mg TID - DB Phase (Titration Plus Maintenance)	52.1	52.7	52.7	53.2

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carbamates and Liver Diseases