Page last updated: 2024-10-16

carbamates and Fatigue

carbamates has been researched along with Fatigue in 17 studies

Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.

Research Excerpts

ExcerptRelevanceReference
"gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV)."9.51Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. ( Dong, M; Evon, DM; Lok, AS; Michael, L; Nelson, DR; Peter, J; Reeve, BB; Stewart, PW, 2022)
"gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV)."5.51Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. ( Dong, M; Evon, DM; Lok, AS; Michael, L; Nelson, DR; Peter, J; Reeve, BB; Stewart, PW, 2022)
"Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily."5.30Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Dutriaux, C; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D; Sileni, VC; Yamazaki, N, 2019)
" However, information about the rate of adverse events (AEs) across different DAA regimens is limited."2.87Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study. ( Andersen, ES; Bukh, J; Christensen, PB; Fahnøe, U; Gerstoft, J; Kjær, MS; Laursen, AL; Mössner, B; Pedersen, MS; Røge, BT; Schønning, K; Sølund, C; Weis, N, 2018)
" We calculated the risk ratio (RR) of ≥50%, ≥75% and 100% reduction in seizure frequency from baseline, as well as dropout and serious adverse events related to treatment."2.72Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis. ( Wang, C; Wang, J; Zhang, L, 2021)
"Few studies have investigated restless legs syndrome (RLS) treatment effects on individual International RLS Study Group Rating Scale (IRLS) items."2.53Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. ( Ahmed, M; Hays, R; Jaros, MJ; Kim, R; Shang, G; Steven Poceta, J, 2016)
"Only fatigue was reported as side effect during the treatment."1.56Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient. ( Chen, J; Lei, P; Li, G; Li, Y, 2020)
"HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU)."1.43Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study. ( Aichelburg, MC; Bucsics, T; Chromy, D; Grabmeier-Pfistershammer, K; Mandorfer, M; Peck-Radosavljevic, M; Reiberger, T; Scheiner, B; Schwabl, P; Steiner, S; Trauner, M, 2016)
" To examine the potential for drug-drug interactions at these two transporters, the pharmacokinetics of gabapentin enacarbil were evaluated in healthy adults after administration alone or in combination with either naproxen (an MCT-1 substrate) or cimetidine (an OCT2 substrate)."1.36Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. ( Blumenthal, R; Cundy, KC; Ho, J; Lal, R; Luo, W; Sukbuntherng, J; Vicente, V, 2010)

Research

Studies (17)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's14 (82.35)24.3611
2020's3 (17.65)2.80

Authors

AuthorsStudies
Evon, DM1
Dong, M1
Reeve, BB1
Peter, J1
Michael, L1
Lok, AS1
Nelson, DR1
Stewart, PW1
Gogas, HJ1
Flaherty, KT1
Dummer, R1
Ascierto, PA1
Arance, A1
Mandala, M1
Liszkay, G1
Garbe, C1
Schadendorf, D1
Krajsova, I1
Gutzmer, R1
Sileni, VC1
Dutriaux, C1
de Groot, JWB1
Yamazaki, N1
Loquai, C1
Gollerkeri, A1
Pickard, MD1
Robert, C1
Cursino, CN1
Monteiro, PGO1
Duarte, GDS1
Vieira, TBQ1
Crisante, VC1
Giordani, F1
Xavier, AR1
de Almeida, RMVR1
Calil-Elias, S1
Chen, J1
Li, Y1
Li, G1
Lei, P1
Zhang, L1
Wang, J2
Wang, C1
Sølund, C1
Andersen, ES1
Mössner, B1
Laursen, AL1
Røge, BT1
Kjær, MS1
Gerstoft, J1
Christensen, PB1
Pedersen, MS1
Schønning, K1
Fahnøe, U1
Bukh, J1
Weis, N1
Zignego, AL1
Monti, M1
Gragnani, L1
Lee, YJ1
Heo, J1
Kim, DY1
Chung, WJ1
Tak, WY1
Kim, YJ1
Paik, SW1
Sim, E1
Kulasingam, S1
Talwani, R1
Haber, B1
Hwang, P1
Zeuzem, S1
Ghalib, R1
Reddy, KR1
Pockros, PJ1
Ben Ari, Z1
Zhao, Y1
Brown, DD1
Wan, S1
DiNubile, MJ1
Nguyen, BY1
Robertson, MN1
Wahl, J1
Barr, E1
Butterton, JR1
Mangia, A1
Arleo, A1
Copetti, M1
Miscio, M1
Piazzolla, V1
Santoro, R1
Squillante, MM1
Stern, R1
Hametner, S1
Ramona, AZ1
Moser, S1
Karpi, A1
Laferl, H1
Stauber, RE1
Zoller, HM1
Maieron, A1
Vogel, W1
Graziadei, I1
Gschwantler, M1
Kozbial, K1
Freissmuth, C1
Hofer, H1
Ferenci, P1
Ahmed, M1
Hays, R1
Steven Poceta, J1
Jaros, MJ1
Kim, R1
Shang, G1
Scheiner, B1
Schwabl, P1
Steiner, S1
Bucsics, T1
Chromy, D1
Aichelburg, MC1
Grabmeier-Pfistershammer, K1
Trauner, M1
Peck-Radosavljevic, M1
Reiberger, T1
Mandorfer, M1
Yao, Y1
Yue, M1
Chen, H1
Liu, M1
Zang, F1
Li, J1
Zhang, Y1
Huang, P1
Yu, R1
Lal, R1
Sukbuntherng, J1
Luo, W1
Vicente, V1
Blumenthal, R1
Ho, J1
Cundy, KC1
Gil-Nagel, A1
Brodie, MJ1
Leroy, R1
Cyr, T1
Hall, S1
Castiglia, M1
Twomey, C1
VanLandingham, K1

Clinical Trials (11)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders[NCT02786537]Phase 41,275 participants (Actual)Interventional2016-06-30Completed
A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma[NCT01909453]Phase 3921 participants (Actual)Interventional2013-12-13Active, not recruiting
Open-Labeled Trial Of Direct-Acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors[NCT02743897]Phase 1/Phase 262 participants (Actual)Interventional2016-05-01Completed
A Prospective Cohort Study to Improve HCV Care Using Multidisciplinary Approach to the Treatment of Chronic Hepatitis C in Dialysis Patients: The MATCH-D Study[NCT03791814]Phase 40 participants (Actual)Interventional2019-01-01Withdrawn (stopped due to The study was stopped due to difficulty in identifying potential patients.)
An Open-label, Cohort Study of Grazoprevir/Elbasvir Combination Therapy for Patients With Genotype 1b Chronic Hepatitis C After Liver or Kidney Transplantation[NCT03723824]Phase 414 participants (Actual)Interventional2019-02-14Terminated (stopped due to COV-19 pandemic)
Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors[NCT03146741]Phase 1/Phase 220 participants (Actual)Interventional2017-05-16Completed
Effect Of Interferon-Free Direct Acting Antiviral Agents For Treatment Of Hepatitis C Virus Patients On The Normal Kidney[NCT03296930]Phase 4100 participants (Anticipated)Interventional2017-10-01Not yet recruiting
A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT1, GT4, and GT6 Infection.[NCT02105467]Phase 3421 participants (Actual)Interventional2014-06-05Completed
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of XP13512 in Patients With Restless Legs Syndrome.[NCT00298623]Phase 3222 participants (Actual)Interventional2006-03-31Completed
A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Efficacy, Safety, and Pharmacokinetics of XP13512 (GSK1838262) in Patients With Restless Legs Syndrome[NCT01332305]Phase 2217 participants (Actual)Interventional2007-01-31Completed
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of XP13512 in Patients With Restless Legs Syndrome.[NCT00365352]Phase 3325 participants (Actual)Interventional2006-08-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

16 Wk EBR/GZR With RBV Efficacy on Patients With HCV RASs

"Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms).~Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients." (NCT02786537)
Timeframe: 12 weeks post treatment

InterventionParticipants (Count of Participants)
EBR/GZR With RBV-16 Weeks34

HCV SVR Durability -No Cirrhosis

Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment. (NCT02786537)
Timeframe: 24 weeks post-end of treatment up to 153 weeks

InterventionParticipants (Count of Participants)
EBR/GZR255
EBR/GZR With Ribavirin17
SOF/LDV146
SOF/LDV With RBV2
PrOD14
PrOD With RBV36

HCV SVR Durability-Patients With Cirrhosis

Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment. (NCT02786537)
Timeframe: Up to 132 weeks post HCV treatment

InterventionParticipants (Count of Participants)
EBR/GZR43
EBR/GZR With RBV7
SOF/LDV35
SOF/LDV With RBV7
PrOD6
PrOD With RBV7

Mean Change in Fatigue PRO -EBR/GZR vs SOF/LDV

Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline and Average On-Treatment Score

Interventionscore on a scale (Mean)
EBR/GZR With RBV-1.0
EBR/GZR-2.1
SOF/LDV With RBV-3.7
SOF/LDV-2.2

Mean Change in Fatigue PRO Score -Phase 1

Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline to On-treatment

Interventionunits on a scale (Mean)
EBR/GZR With RBV1.5
EBR/GZR-1.2
SOF/LDV With RBV-7.2
SOF/LDV-2.0
PrOD With RBV-1.9
PrOD-3.0

Mean Change in HCV- PRO- Phase 1

"HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Baseline to End of Treatment

Interventionunits on a scale (Mean)
EBR/GZR With RBV-0.9
EBR/GZR5.6
SOF/LDV With RBV2.5
SOF/LDV6.9
PrOD With RBV3.2
PrOD9.9

Mean Change in HCV-PRO (Functional Well-being) EBR/GZR vs. SOF/LDV Score-Phase 2

"HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2." (NCT02786537)
Timeframe: End of Treatment - Baseline

Interventionscore on a scale (Mean)
EBR/GZR With RBV3.2
EBR/GZR6.1
SOF/LDV With RBV6.3
SOF/LDV6.8

Mean Change in Headache-EBR/GZR and SOF/LDV

Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: Baseline to On-Treatment

Interventionunits on a scale (Mean)
EBR/GZR With RBV-0.8
EBR/GZR-0.7
SOF/LDV With RBV0.4
SOF/LDV-0.8

Mean Change in Headache-PRO Scores -Phase 1

Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom. (NCT02786537)
Timeframe: Baseline to On-Treatment

Interventionunits on a scale (Mean)
EBR/GZR With Ribavirin (RBV)0.0
EBR/GZR Regimen-0.8
SOF/LDV With RBV-0.7
SOF/LDV-0.5
PrOD With RBV Regimen-0.2
PrOD-2.2

Mean Change in Nausea/Vomiting PRO Score -Phase 1

"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.~The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status." (NCT02786537)
Timeframe: Baseline to On-Treatment

Interventionunits on a scale (Mean)
EBR/GZR With RBV1.3
EBR/GZR-1.4
SOF/LDV With RBV-3.9
SOF/LDV-0.7
PrOD With RBV2.5
PrOD0.7

Mean Change in Nausea/Vomiting PROMIS Score -EBR/GZR vs. LDV/SOF

"Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting.~Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment.~A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline and Average On-Treatment Score

Interventionunits on a scale (Mean)
EBR/GZR With RBV-0.3
EBR/GZR-0.6
SOF/LDV With RBV-1.6
SOF/LDV-0.4

Median Change in Fatigue -Phase 1

Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline to End of Treatment

Interventionunits on a scale (Median)
EBR/GZR With RBV2.2
EBR/GZR Regimen-0.9
SOF/LDV With RBV-10.2
SOF/LDV-3.4
PrOD Regimen With RBV-0.2
PrOD-4.1

Median Change in Fatigue-Phase 2

Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline-On Treatment (up to 16 weeks)

Interventionunits on a scale (Median)
EBR/GZR With RBV-1.3
EBR/GZR-1.2
SOF/LDV With RBV-2.4
SOF/LDV-1.4

Median Change in HCV-PRO (Overall Well Being) -Phase 1

"HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Baseline to End of Treatment

Interventionscore on a scale (Median)
EBR/GZR With RBV0.0
EBR/GZR4.3
SOF/LDV With RBV4.7
SOF/LDV4.7
PrOD With RBV3.1
PrOD8.6

Median Change in Headache -Phase 1

Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: 12 weeks (Baseline and Average On-treatment Score)

Interventionunits on a scale (Median)
EBR/GZR (Elbasvir/Grazoprevir) With RBV0.0
EBR/GZR (Elbasvir/Grazoprevir)0.0
SOF/LDV (Sofosbuvir/Ledipasvir) With RBV-2.0
SOF/LDV (Sofosbuvir/Ledipasvir)-1.0
PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) With RBV (Phase 1 Only)0.0
PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir)-1.0

Median Change in Headache-Phase 2

Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: Baseline -on Treatment (12-16 weeks)

Interventionunits on a scale (Median)
EBR/GZR With RBV-1.0
EBR/GZR0.0
SOF/LDV With RBV0.5
SOF/LDV-0.5

Median Change in Nausea PRO Score -Phase 1

"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.~The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline to end of treatment

Interventionunits on a scale (Median)
EBR/GZR With RBV0.4
EBR/GZR0.0
SOF/LDV With RBV-6.1
SOF/LDV0.0
PrOD With RBV0.0
PrOD0.0

Median Change in Nausea PROMIS Score-EBR/GZR SOF/LDV

"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement.~The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline- On Treatment (up to 16 weeks)

Interventionscore on a scale (Median)
EBR/GZR With RBV0.0
EBR/GZR0.0
SOF/LDV With RBV0.0
SOF/LDV0.0

Number of Participants With Adverse Events That Caused Treatment Discontinuation-EBR/GZR vs. LDV/SOF

The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen) (NCT02786537)
Timeframe: Treatment start date through treatment completion (up to 24 weeks)

InterventionParticipants (Count of Participants)
EBR/GZR Regimen12
SOF/LDV Regimen4

Phase 1 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)

"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~Number of subjects reflects participants randomized during Phase 1 only." (NCT02786537)
Timeframe: 12 -24 weeks post-treatment

InterventionParticipants (Count of Participants)
EBR/GZR With RBV9
EBR/GZR108
SOF/LDV With RBV6
SOF/LDV88
PrOD With RBV77
PrOD (Phase 1 Only)42

Phase 1-Sustained Virologic Response (SVR12) mITT With Imputation

"SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only." (NCT02786537)
Timeframe: 12 weeks post-treatment

InterventionParticipants (Count of Participants)
EBR/GZR With RBV9
EBR/GZR108
SOF/LDV With RBV6
SOF/LDV88
PrOD With RBV77
PrOD42

Phase 1/2 Number of Participants With Sustained Virologic Response (SVR12-mITT Without Imputation)

"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2." (NCT02786537)
Timeframe: 12-24 weeks post HCV treatment

InterventionParticipants (Count of Participants)
EBR/GZR With RBV40
EBR/GZR516
SOF/LDV With RBV14
SOF/LDV335

Post-treatment Progression/Regression of Liver Disease-Fib-4

Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis. (NCT02786537)
Timeframe: Baseline to up to 3 years post treatment discontinuation

Interventionscore on a scale (Median)
EBR/GZR, SOF/LDV or PrOD Based HCV Treatment-1.36

Sustained Virologic Response (SVR12) mITT With Imputation-Phase 1 and 2 EBR/GZR, SOF/LDV

"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider).~mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2." (NCT02786537)
Timeframe: 12 weeks post-treatment

InterventionParticipants (Count of Participants)
EBR/GZR With RBV40
EBR/GZR516
SOF/LDV With RBV14
SOF/LDV335

Treatment Non-Adherence Probability Estimates

"The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being Non-adherent if any response was > 1, otherwise they were coded as Adherent. Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD" (NCT02786537)
Timeframe: 12-16 weeks of HCV treatment

Interventionpercentage of patients (Number)
EBR/GZR23
SOF/LDV19
PrOD26

Change in Functional Status (HCV-PRO) Within Treatment

"HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Treatment start date up to 2 years post-treatment

,
Interventionscore on a scale (Mean)
9 months post treatment20 months post treatment
EBR/GZR Regimen8.029.87
SOF/LDV Regimen9.9011.54

Change in HCV-associated Symptoms (PROMIS Measures) After HCV Treatment Initiation

Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement. (NCT02786537)
Timeframe: 1 year post treatment discontinuation (Early post-tx)

,
Interventionunits on a scale (Mean)
NauseaBelly PainDiarrheaFatigueSleep DisturbanceCognitive ImpairmentHCV-PRO
EBR/GZR Regimen0.00-0.82-1.12-2.080.65-0.548.02
SOF/LDV Regimen-4.99-6.47-5.77-7.59-1.72-4.489.90

Impact of Baseline NS5A RASs on Treatment Outcomes-Phase 2

Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen (NCT02786537)
Timeframe: 12 weeks post HCV treatment

,
InterventionParticipants (Count of Participants)
With NS5a RASWithout NS5a RAS
EBR/GZR Regimen47485
SOF/LDV Regimen42286

Part 1 and Part 2: Disease Control Rate (DCR)

DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionpercentage of participants (Number)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)92.2
Part 1: LGX818 300 mg84.0
Part 1: Vemurafenib 960 mg BID81.7
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)90.7
Part 2: LGX818 300 mg79.1
Part 1 + Part 2: LGX818 300 mg82.5

Part 1 and Part 2: Duration of Response (DOR)

DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)16.6
Part 1: LGX818 300 mg15.2
Part 1: Vemurafenib 960 mg BID12.3
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)12.7
Part 2: LGX818 300 mg7.5
Part 1 + Part 2: LGX818 300 mg12.9

Part 1 and Part 2: Objective Response Rate (ORR)

ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionpercentage of participants (Number)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)63.0
Part 1: LGX818 300 mg50.5
Part 1: Vemurafenib 960 mg BID40.3
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)65.9
Part 2: LGX818 300 mg50.0
Part 1 + Part 2: LGX818 300 mg50.4

Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)NA
Part 1: LGX818 300 mg26.7
Part 1: Vemurafenib 960 mg BID18.2
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)NA
Part 2: LGX818 300 mg10.2
Part 1 + Part 2: LGX818 300 mg19.2

Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale

FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause. (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)NA
Part 1: LGX818 300 mg30.5
Part 1: Vemurafenib 960 mg BID22.1
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)NA
Part 2: LGX818 300 mgNA
Part 1 + Part 2: LGX818 300 mg20.5

Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

"EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from not at all to very much and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause." (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)23.9
Part 1: LGX818 300 mg14.7
Part 1: Vemurafenib 960 mg BID16.6
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18.4
Part 2: LGX818 300 mg9.5
Part 1 + Part 2: LGX818 300 mg11.1

Part 1 and Part 2: Time to Objective Response (TTR)

TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit [FPFV] to last patient last visit [LPLV] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)1.9
Part 1: LGX818 300 mg2.0
Part 1: Vemurafenib 960 mg BID2.1
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1.9
Part 2: LGX818 300 mg1.9
Part 1 + Part 2: LGX818 300 mg1.9

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)14.9
Part 1: LGX818 300 mg9.6

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm^2). (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)14.9
Part 1: Vemurafenib 960 mg BID7.3

Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)

Interventionmonths (Median)
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)12.9
Part 2: LGX818 300 mg7.4
Part 1 + Part 2: LGX818 300 mg9.2

Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg74.201.792.96-3.62-0.60-2.69-6.41-2.121.792.7816.675.56
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)73.047.296.159.379.2210.568.6610.5910.338.3313.13-4.17

Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg74.380.321.98-0.911.26-0.740.831.303.261.27-0.762.94-0.32-0.83
Part 1: LGX818 300 mg74.46-0.341.540.342.150.123.782.303.641.00-1.162.94-0.32-3.57
Part 1: Vemurafenib 960 mg BID72.311.882.032.71-0.174.53-2.25-5.46-1.390.38-3.13-0.69-1.1912.50
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)74.683.235.375.424.474.813.527.355.334.254.17-1.743.9241.67

Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg0.73-0.06-0.06-0.16-0.11-0.16-0.20-0.26-0.20-0.11-0.11-0.06
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)0.750.060.070.060.070.060.050.050.060.050.12-0.27

Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg0.75-0.09-0.13-0.14-0.14-0.17-0.18-0.20-0.15-0.17-0.14-0.11-0.11-0.08
Part 1: LGX818 300 mg0.76-0.10-0.15-0.13-0.15-0.18-0.17-0.18-0.14-0.18-0.14-0.11-0.11-0.09
Part 1: Vemurafenib 960 mg BID0.730.00-0.04-0.03-0.04-0.01-0.02-0.07-0.02-0.02-0.04-0.05-0.17-0.14
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)0.740.050.040.050.030.040.050.050.070.030.070.040.070.03

Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg67.39-4.95-4.72-7.08-8.73-7.53-9.29-12.75-7.14-0.930.004.17
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)65.954.475.615.014.944.765.896.115.861.233.03-6.25

Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg66.48-6.81-7.87-8.53-10.96-10.13-8.80-10.56-7.85-8.05-10.80-5.64-7.054.63
Part 1: LGX818 300 mg66.07-7.64-9.24-9.21-12.03-11.27-8.59-9.91-8.03-9.33-11.05-5.64-7.054.76
Part 1: Vemurafenib 960 mg BID64.74-3.46-4.05-3.04-6.94-3.80-2.93-10.34-6.94-1.89-8.85-3.47-2.38-4.17
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)66.723.561.551.53-0.550.810.425.020.41-0.510.74-1.391.960.00

Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg81.45-13.63-12.63-17.01-15.83-13.49-13.85-24.31-19.05-14.07-13.33-4.44
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)80.672.942.731.223.030.500.47-0.40-0.88-5.71-8.48-5.00

Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg82.63-13.74-15.74-16.49-18.27-19.87-18.22-21.18-18.91-19.14-16.78-14.46-15.93-2.00
Part 1: LGX818 300 mg83.18-13.79-17.14-16.26-19.43-22.65-20.00-20.26-18.88-20.07-16.86-14.46-15.93-0.95
Part 1: Vemurafenib 960 mg BID80.71-2.90-7.45-6.98-6.82-4.11-6.30-6.22-3.27-1.90-4.90-2.22-4.76-15.00
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)82.100.200.15-1.93-0.45-0.85-1.250.29-0.03-1.22-0.95-5.00-5.4933.33

Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg78.31-10.00-5.11-13.89-9.52-12.37-5.77-15.69-7.14-12.96-33.330.00
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)81.374.053.373.053.661.951.752.861.591.234.55-16.67

Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg80.09-10.59-9.80-11.11-13.70-12.54-9.74-11.78-10.54-12.43-15.15-6.37-7.05-13.33
Part 1: LGX818 300 mg80.91-10.86-11.92-9.80-15.71-12.62-11.38-10.63-11.42-12.33-14.73-6.37-7.05-19.05
Part 1: Vemurafenib 960 mg BID78.54-4.90-7.21-2.75-1.99-0.36-0.45-6.321.393.79-3.131.394.76-8.33
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)80.69-0.663.262.821.57-2.72-4.273.731.11-1.04-1.52-12.32-5.2125.00

Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg51.13-2.16-0.60-3.14-1.83-2.41-3.31-4.14-2.640.00-2.00-1.61
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)52.082.792.582.643.232.541.972.082.451.232.586.58

Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1: Vemurafenib 960 mg BID52.01-1.55-1.90-2.19-1.90-0.51-0.97-1.720.700.23-3.33-0.17-0.14-2.31
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)52.390.92-0.011.350.520.18-0.330.400.27-0.59-0.69-1.67-1.8318.50
Part 1 + Part 2: LGX818 300 mg52.24-3.14-2.78-3.08-2.39-3.29-2.88-2.88-1.88-2.38-2.58-1.38-1.00-3.81
Part 1: LGX818 300 mg52.76-3.58-3.77-3.05-2.69-3.67-2.71-2.48-1.66-2.80-2.59-1.38-1.00-5.18

Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. (NCT01909453)
Timeframe: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)

,,,,,
InterventionParticipants (Count of Participants)
Baseline: ECOG score 0Baseline: ECOG score 1Cycle 2 Day 1: ECOG score 0Cycle 2 Day 1: ECOG score 1Cycle 2 Day 1: ECOG score 2Cycle 2 Day 1: ECOG score 3Cycle 2 Day 1: ECOG score 4Cycle 3 Day 1: ECOG score 0Cycle 3 Day 1: ECOG score 1Cycle 3 Day 1: ECOG score 2Cycle 4 Day 1: ECOG score 0Cycle 4 Day 1: ECOG score 1Cycle 4 Day 1: ECOG score 2Cycle 4 Day 1: ECOG score 3Cycle 5 Day 1: ECOG score 0Cycle 5 Day 1: ECOG score 1Cycle 5 Day 1: ECOG score 2Cycle 5 Day 1: ECOG score 3Cycle 5 Day 1: ECOG score 4Cycle 6 Day 1: ECOG score 0Cycle 6 Day 1: ECOG score 1Cycle 6 Day 1: ECOG score 2Cycle 6 Day 1: ECOG score 3Cycle 6 Day 1: ECOG score 4Cycle 7 Day 1: ECOG score 0Cycle 7 Day 1: ECOG score 1Cycle 7 Day 1: ECOG score 2Cycle 8 Day 1: ECOG score 0Cycle 8 Day 1: ECOG score 1Cycle 8 Day 1: ECOG score 2Cycle 8 Day 1: ECOG score 3Cycle 9 Day 1: ECOG score 0Cycle 9 Day 1: ECOG score 1Cycle 9 Day 1: ECOG score 2Cycle 9 Day 1: ECOG score 3Cycle 9 Day 1: ECOG score 4Cycle 9 Day 1: ECOG score 5Cycle 10 Day 1: ECOG score 0Cycle 10 Day 1: ECOG score 1Cycle 10 Day 1: ECOG score 2Cycle 10 Day 1: ECOG score 3Cycle 11 Day 1: ECOG score 0Cycle 11 Day 1: ECOG score 1Cycle 11 Day 1: ECOG score 2Cycle 11 Day 1: ECOG score 3Cycle 12 Day 1: ECOG score 0Cycle 12 Day 1: ECOG score 1Cycle 12 Day 1: ECOG score 2Cycle 12 Day 1: ECOG score 3Cycle 12 Day 1: ECOG score 4Cycle 13 Day 1: ECOG score 0Cycle 13 Day 1: ECOG score 1Cycle 13 Day 1: ECOG score 2Cycle 13 Day 1: ECOG score 4Cycle 14 Day 1: ECOG score 0Cycle 14 Day 1: ECOG score 1Cycle 14 Day 1: ECOG score 2Cycle 14 Day 1: ECOG score 3Cycle 14 Day 1: ECOG score 4Cycle 15 Day 1: ECOG score 0Cycle 15 Day 1: ECOG score 1Cycle 15 Day 1: ECOG score 2Cycle 15 Day 1: ECOG score 3Cycle 15 Day 1: ECOG score 4Cycle 16 Day 1: ECOG score 0Cycle 16 Day 1: ECOG score 1Cycle 16 Day 1: ECOG score 2Cycle 16 Day 1: ECOG score 3Cycle 17 Day 1: ECOG score 0Cycle 17 Day 1: ECOG score 1Cycle 17 Day 1: ECOG score 2Cycle 18 Day 1: ECOG score 0Cycle 18 Day 1: ECOG score 1Cycle 18 Day 1: ECOG score 2Cycle 18 Day 1: ECOG score 3Cycle 19 Day 1: ECOG score 0Cycle 19 Day 1: ECOG score 1Cycle 19 Day 1: ECOG score 2Cycle 20 Day 1: ECOG score 0Cycle 20 Day 1: ECOG score 1Cycle 20 Day 1: ECOG score 2Cycle 20 Day 1: ECOG score 3Cycle 21 Day 1: ECOG score 0Cycle 21 Day 1: ECOG score 1Cycle 21 Day 1: ECOG score 2Cycle 22 Day 1: ECOG score 0Cycle 22 Day 1: ECOG score 1Cycle 22 Day 1: ECOG score 3Cycle 22 Day 1: ECOG score 4Cycle 23 Day 1: ECOG score 0Cycle 23 Day 1: ECOG score 1Cycle 24 Day 1: ECOG score 0Cycle 24 Day 1: ECOG score 1Cycle 25 Day 1: ECOG score 0Cycle 25 Day 1: ECOG score 1Cycle 26 Day 1: ECOG score 0Cycle 26 Day 1: ECOG score 1Cycle 26 Day 1: ECOG score 2Cycle 27 Day 1: ECOG score 0Cycle 27 Day 1: ECOG score 1Cycle 28 Day 1: ECOG score 0Cycle 28 Day 1: ECOG score 1Cycle 29 Day 1: ECOG score 0Cycle 29 Day 1: ECOG score 1Cycle 30 Day 1: ECOG score 0Cycle 30 Day 1: ECOG score 1Cycle 31 Day 1: ECOG score 0Cycle 31 Day 1: ECOG score 1
Part 1 + Part 2: LGX818 300 mg1997714211172013011361289671118100600979061195872777061726711007053206156405549210554630623720154372005230404833241290040261342220312012716112612231023821802061861359373
Part 1: LGX818 300 mg139539879320908149366418569400686530168601554931504710005235104440104431110413110472700141301004123303927136240038201311920291912716112612231023821802061861359373
Part 1: Vemurafenib 960 mg BID13551113644001076449852448252711784611074352583340553041004326213920213216210271820251920022181002410102111118111120911980015801160010595927203441504020
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)136561424410113153112850101284231012445000111461112332110236401194323088302084251007722107423000722011064241065161601410549253701361092980024621717314315353120000
Part 2: LGX818 300 mg602444324004032235303033312002925310272712221302220010018181017163011181001415201510200137100117109615500260330021000000000000000000000000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18968193621001975511895641181552101685831115858214058111355200101214631116420011338001102391110033210822710164230152151341110227115500112042000000000000000000000

Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Hemoglobin (hypo)Prothrombin international normalized ratio increasedLymphocytes (hypo)Lymphocytes (hyper)Neutrophils (hypo)Platelets (hypo)Leukocytes (hypo)Albumin (hypo)Alkaline phosphataseAlanine aminotransferaseAspartate aminotransferaseBilirubinCreatine (phospho)kinaseCorrected Calcium (hypo)Corrected Calcium (hyper)CreatinineGamma-glutamyl transferaseGlucose serum fasting (hypo)Glucose serum fasting (hyper)Magnesium (hypo)Magnesium (hyper)Phosphate (hypo)Potassium (hypo)Potassium (hyper)Sodium (hypo)
Part 1: LGX818 300 mg11115115135384011015294121025141
Part 1: Vemurafenib 960 mg BID13341531424841313248153120135361
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)190201414253615121321035432200218167

Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
RashSkin infectionsPPE syndromePhotosensitivityNail disordersSevere cutaneous adverse reactions
Part 1: LGX818 300 mg10126001
Part 1: Vemurafenib 960 mg BID2502305
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)240100

Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values

Newly occurring notable ECG values were reported for QT (millisecond [ms]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (>) 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60. Heart rate: New <60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
QT: Increase >30 msQT: Increase >60 msQT: New >450 msQT: New >480 msQT: New >500 msQTcF: Increase >30 msQTcF: Increase >60 msQTcF: New >450 msQTcF: New >480 msQTcF: New >500 msQTcB: Increase >30 msQTcB: Increase >60 msQTcB: New >450 msQTcB: New >480 msQTcB: New >500 msHeart rate: New <60 bpmHeart rate: New <100 bpm
Part 1: LGX818 300 mg68191542567397574157623103723
Part 1: Vemurafenib 960 mg BID81241732761042537814652081618
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)105272352501025714711471235814

Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high diastolic blood pressure (DBP) [mmHg]: <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 beats per minute (bpm) with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight [kilogram]: >=20 percent (%) decrease from baseline/>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): <= 36 degree C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Sitting Pulse Rate (bpm): HighSitting Pulse Rate (bpm): LowSitting Systolic Blood Pressure (mmHg): HighSitting Systolic Blood Pressure (mmHg): LowSitting Diastolic Blood Pressure (mmHg): HighSitting Diastolic Blood Pressure (mmHg): LowWeight (kg): HighWeight (kg): LowBody temperature (degree C): HighBody temperature (degree C): Low
Part 1: LGX818 300 mg78144571081174
Part 1: Vemurafenib 960 mg BID823111358131757
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)132772394421976

Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Retinopathy excluding RVORVOUveitis-type events
Part 1: LGX818 300 mg010
Part 1: Vemurafenib 960 mg BID000
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)501

Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Grade 0Grade 2Grade 3Grade 4Missing
Part 1: LGX818 300 mg161174010
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)12756306
Part 1: Vemurafenib 960 mg BID16116207

Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
Interventionpercentage of participants (Number)
Participants with AEsParticipants with SAEs
Part 1: LGX818 300 mg99.534.9
Part 1: Vemurafenib 960 mg BID99.537.1
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)98.434.4

Part 1: Plasma Concentrations of LGX 818

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

,
Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1: LGX818 300 mg58.111904090185073.653.8
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)18.6164068603400119150

Part 1: Plasma Concentrations of MEK162

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)2.9542683233081.068.1

Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Hemoglobin (hypo)Prothrombin international normalized ratio increasedLymphocytes (hypo)Lymphocytes (hyper)Neutrophils (hypo)Platelets (hypo)Leukocytes (hypo)Albumin (hypo)Alkaline phosphatase (hyper)Alanine aminotransferaseAspartate aminotransferaseBilirubinCreatine kinaseCorrected Calcium (hypo)CreatinineGamma-glutamyl transferaseGlucose serum fasting (hypo)Glucose serum fasting (hyper)Magnesium (hypo)Magnesium (hyper)Phosphate (hypo)Potassium (hypo)Potassium (hyper)Sodium (hypo)Sodium (hyper)
Part 1 + Part 2: LGX818 300 mg16125139259495012263841710331730
Part 2: LGX818 300 mg501024124111001119050080320
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1642811191371118152404443832703262842

Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
RashSkin infectionPPE syndromePhotosensitivityNail disordersSevere cutaneous adverse reactions
Part 1 + Part 2: LGX818 300 mg13130001
Part 2: LGX818 300 mg304000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)271000

Part 2: Number of Participants With Newly Occurring Notable ECG Values

Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New >450, New >480, New >500, increase from baseline >30, Increase from baseline >60. Heart rate: New < 60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
QT (ms): Increase from baseline > 30QT (ms): Increase from baseline > 60QT (ms): New > 450QT (ms): New > 480QT (ms): New > 500QTcF (ms): Increase from baseline > 30QTcF (ms): Increase from baseline > 60QTcF (ms): New > 450QTcF (ms): New > 480QTcF (ms): New > 500QTcB (ms): New > 450QTcB (ms): New > 480QTcB (ms): New > 500QTcB (ms): Increase from baseline > 30QTcB (ms): Increase from baseline > 60Heart rate (bpm): New < 60Heart rate (bpm): New > 100
Part 1 + Part 2: LGX818 300 mg95252062761450126104291198234233
Part 2: LGX818 300 mg27652020711512861248510
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1323434945913361127023106922828

Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg, Low/high diastolic blood pressure (DBP) [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg, Low/high pulse rate [bpm]: <=50 bpm with decrease from baseline of >=15 bpm/>=120 bpm with increase from baseline of >=15 bpm, Low/high weight (kg): >=20 % decrease from baseline/>= 10% increase from baseline Low/high Body temperature degree C): <= 36°C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Sitting Pulse Rate (bpm): HighSitting Pulse Rate (bpm): LowSitting Systolic Blood Pressure (mmHg): HighSitting Systolic Blood Pressure (mmHg): LowSitting Diastolic Blood Pressure (mmHg): HighSitting Diastolic Blood Pressure (mmHg): LowWeight (kg): HighWeight (kg): LowBody temperature (°C): HighBody temperature (°C): Low
Part 1 + Part 2: LGX818 300 mg109178791191696
Part 2: LGX818 300 mg31342211522
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)711401041746014120

Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Retinopathy excluding RVORVOUveitis-type events
Part 1 + Part 2: LGX818 300 mg010
Part 2: LGX818 300 mg000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)404

Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Grade 0Grade 2Grade 3Grade 4Missing
Part 1 + Part 2: LGX818 300 mg235224015
Part 2: LGX818 300 mg745005
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18171302

Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
Interventionpercentage of Participants (Number)
AEsSAEs
Part 1 + Part 2: LGX818 300 mg98.633.3
Part 2: LGX818 300 mg96.429.8
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)98.129.2

Part 2: Plasma Concentrations of LGX 818

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

,,
Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1 + Part 2: LGX818 300 mg39.712504170198060.160.6
Part 2: LGX818 300 mg0.014513704310225029.579.5
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)5.0213604390242012174.1

Part 2: Plasma Concentrations of MEK162

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1.6836664228772.373.2

Number of Subjects Cured

Subjects with post-treatment sustained virologic response (SVR) = Number of subjects with negative HCV RNA 12 weeks after completing therapy / number of subjects treated post-kidney transplantation (NCT02743897)
Timeframe: Baseline to 24 weeks

InterventionParticipants (Count of Participants)
Direct-acting Antiviral Treatment for HCV62

Number of Subjects With SAE Attributable to HCV Therapy

Number of subjects with major adverse events attributable to HCV therapy in post-kidney transplant (NCT02743897)
Timeframe: Baseline to 52 weeks

InterventionParticipants (Count of Participants)
Direct-acting Antiviral Treatment for HCV1

Number of Participants With Post-treatment Sustained Virologic Response (SVR)

The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation) (NCT03146741)
Timeframe: Baseline to 24 weeks

InterventionParticipants (Count of Participants)
Zepatier (Grazoprevir 100mg and Elbasvir 50 mg)9

Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant

(NCT03146741)
Timeframe: Baseline to 52 weeks

InterventionSevere adverse event (Number)
Zepatier (Grazoprevir 100mg and Elbasvir 50 mg)0

Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12)

Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA NCT02105467)
Timeframe: Week 24 (12 weeks after the end of treatment)

InterventionPercentage of participants (Number)
Immediate Treatment Group94.6

Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24)

Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA NCT02105467)
Timeframe: Week 36 (24 weeks after the end of treatment)

InterventionPercentage of participants (Number)
Immediate Treatment Group94.3

Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4)

Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA NCT02105467)
Timeframe: Week 16 (4 weeks after the end of treatment)

InterventionPercentage of participants (Number)
Immediate Treatment Group97.2

Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT02105467)
Timeframe: Up to Week 12 (end of Blinded Treatment)

InterventionPercentage of participants (Number)
Immediate Treatment Group0.9
Deferred Treatment Group1.0

Percentage of Participants Experiencing at Least One Adverse Event

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT02105467)
Timeframe: Up to Week 14 (14 days after the Blinded Treatment was completed)

InterventionPercentage of participants (Number)
Immediate Treatment Group67.4
Deferred Treatment Group68.6

Mean AUCss

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUCss is the area under the curve during the steady-state period. The AUCss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUCss used concentration data from 0 to 24 hours at steady-state for Weeks 4 and 12. (NCT01332305)
Timeframe: Weeks 4 and 12

,,,
Interventionng*hour/ml (Mean)
Week 4, n=0, 38, 33, 33, 35Week 12, n=0, 32, 30, 30, 30
GEn 1200 mg96.195.7
GEn 1800 mg141146
GEn 2400 mg176173
GEn 600 mg49.351.4

Mean Css, Max and Css, Min

"Css, max is defined as the maximum or peak concentration of a drug observed after multiple administration, at steady state. Css, max is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Css, min is defined as the minimum concentration of a drug observed after its administration, in steady state. ng, nanograms; PK, pharmacokinetic; W, week; BLQ, below limit of quantitation." (NCT01332305)
Timeframe: Weeks 4 and 12

,,,
Interventionnanograms per milliliter (ng/ml) (Mean)
Css, max; Week 4, n=0, 39, 33, 33, 36Css, max; Week 12, n=0, 32, 30, 30, 31Css, min; Week 4, n=0, 39, 33, 33, 36Css, min; Week 12, n=0, 32, 30, 30, 31
GEn 1200 mg7.147.151.371.32
GEn 1800 mg11.412.01.631.60
GEn 2400 mg14.013.32.342.41
GEn 600 mg3.864.140.6900.600

Mean Tmax and T1/2

"Tmax is defined as the time to the maximum or peak concentration of a drug observed after multiple administration. T1/2 is defined as the time to when half of the total amount of a particular substance is eliminated from the body." (NCT01332305)
Timeframe: Weeks 4 and 12

,,,
Interventionhours (Mean)
Tmax; Week 4, n=0, 39, 33, 33, 36Tmax; Week 12, n=0, 32, 30, 30, 31T1/2; Week 4, n=0, 38, 33, 33, 35T1/2, Week 12, n=0, 32, 30, 30, 30
GEn 1200 mg8.578.726.676.63
GEn 1800 mg7.618.005.825.89
GEn 2400 mg8.018.136.056.09
GEn 600 mg8.766.965.826.27

"Number of Participants With a Score of Much Improved or Very Much Improved on the Investigator-rated CGI-I Scale (Response) at (Week 12) Using LOCF"

"The investigator -rated Clinical Global Impression of Improvement (CGI-I) scale is an assessment designed to allow investigators to rate the change of a participant's disease severity over time based on a seven-point scale, with a score of 1 being very much improved, a score of 2 being much improved, a score of 3 being minimally improved, a score of 4 being no change, a score of 5 being minimally improved,a score of 6 being much worse, and a score of 7 being very much worse. Participants with a response of much improved or very much improved were classified as responders." (NCT00365352)
Timeframe: Week 12

Interventionparticipants (Number)
Placebo43
GEn (XP13512/GSK1838262) 1200 mg86

Change From Baseline in IRLS Rating Scale Total Score at Week 12 Using Last Observation Carried Forward (LOCF)

The International Restless Legs Syndrome (IRLS) Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline and Week 12

Interventionscores on a scale (Mean)
Placebo-9.8
GEn (XP13512/GSK1838262) 1200 mg-13.0

Change From Baseline in Sleep Adequacy, an Item on the MOS Sleep Scale, at Week 12 Using LOCF

"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep adequacy domain ranged from 1 to 100, with a high score indicating greater adequacy. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Basline and Week 12

Interventionscores on a scale (Mean)
Placebo13.6
GEn (XP13512/GSK1838262) 600 mg29.1
GEn (XP13512/GSK1838262) 1200 mg27.7

Change From Baseline in Sleep Quantity, an Item on the MOS Sleep Scale, at Week 12 Using LOCF

"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep quantity domain were measured in time (number of hours of sleep each night). The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12

Interventionhours (Mean)
Placebo0.3
GEn (XP13512/GSK1838262) 600 mg0.6
GEn (XP13512/GSK1838262) 1200 mg0.8

Change From Baseline in the Average Daily RLS Pain Score at the End of Treatment (Week 12) for Participants With Pain at Baseline or the End of Week 12 Using LOCF

The Daily RLS pain score was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined study visits. The change from baseline was calculated as the End of Treatment (Week 12) value minus the Baseline (Day 1) value. (NCT00365352)
Timeframe: Baseline and End of Treatment (Week 12)

Interventionscores on a scale (Mean)
Placebo-1.7
GEn (XP13512/GSK1838262) 600 mg-2.5
GEn (XP13512/GSK1838262) 1200 mg-2.6

Change From Baseline in the Average Daily RLS Pain Score to Week 12 for Participants With a Baseline Pain Score of at Least 4 Using LOCF

The Average Daily RLS pain was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined visits. The change from baseline was calculated as the End of Treatment (Week 12) value minus the Baseline (Day 1) value. (NCT00365352)
Timeframe: Baseline and Week 12

Interventionscores on a scale (Mean)
Placebo-2.3
GEn (XP13512/GSK1838262) 600 mg-3.5
GEn (XP13512/GSK1838262) 1200 mg-3.5

Change From Baseline in the Daytime Somnolence Score, an Item on the Medical Outcomes Study (MOS) Sleep Scale, at Week 12 Using LOCF

"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the daytime somnolence domain ranged from 1 to 100, with a high score indicating greater daytime somnolence. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12

Interventionscores on a scale (Mean)
Placebo-9.7
GEn (XP13512/GSK1838262) 600 mg-9.8
GEn (XP13512/GSK1838262) 1200 mg-16.1

Change From Baseline in the Overall Life-Impact Score of the RLS Quality of Life (QoL) Questionnaire at Week 12 Using LOCF

The Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire is a disease-specific, participant-rated questionnaire that assesses the impact of RLS on daily life, emotional well-being, social life, and work life of the participants. The RLS-QoL Questionnaire is presented on a 0 (lowest possible score) to 100 (highest possible score) scale. It was completed at Day 1 and at the end of Weeks 4, 8, and 12 (or Early Termination). (NCT00365352)
Timeframe: Baseline and Week 12

Interventionscores on a scale (Mean)
Placebo14.5
GEn (XP13512/GSK1838262) 600 mg19.3
GEn (XP13512/GSK1838262) 1200 mg20.4

Change From Baseline in the Profile of Mood State (POMS) Scale at Week 12 Using LOCF

"The Profile of Mood States (POMS) Brief Form contains 30 adjectives; each participant is asked to rate the degree to which each adjective describes themselves based on how they felt during the past week including the date on which the adjective was rated. The possible ratings range from 0 (Not all all) to 4 (Extremely). The Total Mood Disturbance Score (range of 0 to 120) is obtained by summing the values of six domains. Higher scores indicate a more negative mood disturbance. The POMS was completed at Baseline (Day 1), and at the end of Weeks 4, 8, and 12 (or Early Termination)." (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)

Interventionscores on a scale (Mean)
Placebo-7.3
GEn (XP13512/GSK1838262) 600 mg-10.9
GEn (XP13512/GSK1838262) 1200 mg-11.5

Change From Baseline in the Sleep Disturbance Score, an Item on the MOS Sleep Scale, at Week 12 Using LOCF

"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep disturbance domain ranged from 1 to 100, with a high score indicating greater impairment of sleep. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12

Interventionscores on a scale (Mean)
Placebo-17.0
GEn (XP13512/GSK1838262) 600 mg-29.5
GEn (XP13512/GSK1838262) 1200 mg-30.7

Change From Baseline to the End of Treatment (Week 12) in the IRLS Rating Scale Total Score Using LOCF

The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and End of Treatment (Week 12)

Interventionscores on a scale (Mean)
Placebo-9.8
GEn (XP13512/GSK1838262) 600 mg-13.8

Change From Baseline to the End of Treatment in Average Daily Total Sleep Time (Hours) Using LOCF

Average daily total sleep time was derived from the Pittsburgh Sleep Diary (PghSD; an instrument with separate components to be completed [self-reported] at bedtime and waketime) as the mean of non-missing total sleep time over the 7 days before each visit, where total sleep time = [(wake up time - lights out time) - time to fall asleep - time awake during the night] in hours. The change was calculated as the end of treatment (Week 12) value minus the Baseline value. (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)

Interventionhours (Mean)
Placebo0.6
GEn (XP13512/GSK1838262) 600 mg0.7
GEn (XP13512/GSK1838262) 1200 mg1.0

Change From Baseline to the End of Treatment in Average Daily Wake Time (Minutes) After Sleep Onset Using LOCF

Average daily wake time after sleep onset was derived from the Pittsburgh Sleep Diary (PghSD) as the mean of non-missing total hours awake during the night after falling asleep over the 7 days before each visit. The change was calculated as the end of treatment (Week 12) value minus the Baseline value. (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)

Interventionminutes (Mean)
Placebo-12.5
GEn (XP13512/GSK1838262) 600 mg-16.4
GEn (XP13512/GSK1838262) 1200 mg-18.5

Change From Baseline to the End of Week 1 in the IRLS Rating Scale Total Score Using LOCF

The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline and the End of Week 1

Interventionscores on a scale (Mean)
Placebo-6.0
GEn (XP13512/GSK1838262) 600 mg-9.8
GEn (XP13512/GSK1838262) 1200 mg-8.7

Number of Participants Classsified as Responders on the Investigator-rated CGI-I Scale at Week 12 Using LOCF

"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Week 12

Interventionparticipants (Number)
Placebo43
GEn (XP13512/GSK1838262) 600 mg83

Number of Participants Who Had an Onset of Response to Treatment at the End of Week 1 Based Upon the IRLS Rating Scale Total Score and the Investigator-rated CGI-I Using LOCF

"The IRLS Rating scale is a measure of RLS disease severity. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. Response was defined by an IRLS Rating Scale total score at the end of Week 1 < 15 and at least a 6-point reduction from the participant's Baseline score and an investigator-rated CGI-I response of much improved or very much improved." (NCT00365352)
Timeframe: End of Week 1

Interventionparticipants (Number)
Placebo13
GEn (XP13512/GSK1838262) 600 mg36
GEn (XP13512/GSK1838262) 1200 mg40

Number of Participants Who Indicated on the Mood Assessment That Their Mood Was Much Improved or Very Much Improved at Week 12 (End of Treatment) Using LOCF

The Mood Assessment is a non-disease-specific question surveying global change in a participant's overall mood. Participants were asked to rate their overall change in mood since the start of the study by choosing a score in a range from 1 (Very Much Improved) to 7 (Very Much Worse). The assessment was completed at Day 1 and the ends of Weeks 4, 8, and 12 or (Early Termination). (NCT00365352)
Timeframe: Week 12

Interventionparticipants (Number)
Placebo19
GEn (XP13512/GSK1838262) 600 mg35
GEn (XP13512/GSK1838262) 1200 mg39

Number of Participants With a Rating of Excellent for the Overall Quality of Sleep in Past Week Measured by the Post-Sleep Questionnaire (PSQ) at the End of Treatment (Week 12) Using LOCF

"The Post-Sleep Questionnaire (PSQ) was designed to evaluate overall sleep quality, ability to function, and RLS symptoms' interference with sleep over the past week. Participants were asked to rate overall sleep quality (as either Excellent, Reasonable, or Poor), ability to function, number of nights with RLS symptoms, number of nights awakened by RLS symptoms, and the number of hours spent awake due to RLS symptoms over the past week." (NCT00365352)
Timeframe: End of Treatment (Week 12)

Interventionparticipants (Number)
Placebo14
GEn (XP13512/GSK1838262) 600 mg24
GEn (XP13512/GSK1838262) 1200 mg30

Number of Total Responders to Treatment Based on the Investigator-Rated CGI of Improvement at the End of One Week of Treatment

"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: End of Week 1

Interventionresponders (Number)
Placebo26
GEn (XP13512/GSK1838262) 600 mg54
GEn (XP13512/GSK1838262) 1200 mg59

The Time to Onset of the First Response to Treatment on the IRLS Rating Scale Total Score and the Investigator-rated CGI-I

The Response was defined by an IRLS Rating Scale total score at the end of Week 1 < 15 and at least a 6-point reduction from the participant's Baseline score and an investigator-rated CGI-I response of much improved or very much improved. The median time to onset is estimated using the product-limit estimation method. (NCT00365352)
Timeframe: Baseline (Day 1) to End of Treatment (Week 12)

Interventionweeks (Median)
PlaceboNA
GEn (XP13512/GSK1838262) 600 Milligrams(mg) Taken Orally4.1
GEn (XP13512/GSK1838262) 1200 mg Taken Orally Once a Day2.1

Time to Onset of the First RLS Symptom From the 24-hour RLS Record Obtained at the End of Treatment (Week 12)

The time to onset of the first RLS symptoms from the 24-hour RLS Record is defined as the length of time from the start of the 24-hour assessment period (8:00 AM) to the time when 50% of participants experienced their first symptom. (NCT00365352)
Timeframe: Week 12

Interventionhours (Median)
Placebo12.8
GEn (XP13512/GSK1838262) 600 mg13.5
GEn (XP13512/GSK1838262) 1200 mg13.8

Change From Baseline in the IRLS Rating Scale Total Score at Week 12 by Baseline RLS Rating Scale Total Score Category (Baseline RLS Severity) Using LOCF

The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and Week 12

,,
Interventionscores on a scale (Mean)
IRLS Total Score < 17.5IRLS Total Score 17.5 to < 22.5IRLS Total Score 22.5 to < 27.5IRLS Total Score >= 27.5
GEn (XP13512/GSK1838262) 1200 mg-7.9-8.8-15.5-19.6
GEn (XP13512/GSK1838262) 600 mg-8.9-11.9-15.1-18.2
Placebo-6.3-8.5-9.6-13.3

Mean Change in the IRLS Rating Scale Total Score From Baseline at Week 12 by RLS Treatment History Using LOCF

The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and Week 12

,,
Interventionscores on a scale (Mean)
No RLS Treatment HistoryTreatment terminatedTreatment within 1 month of study start
GEn (XP13512/GSK1838262) 1200 mg-12.5-17.1-12.1
GEn (XP13512/GSK1838262) 600 mg-13.7-12.4-14.6
Placebo-8.8-13.3-10.7

Number of Participants Classified as Investigator-rated CGI-I Scale Responders at Week 12 by RLS Treatment History Using LOCF

"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Basline and Week 12

,,
Interventionparticipants (Number)
No RLS Treatment HistoryTreatment terminatedTreatment within 1 month of study start
GEn (XP13512/GSK1838262) 1200 mg571315
GEn (XP13512/GSK1838262) 600 mg54918
Placebo26511

Number of Participants Classified as Responders to Treatment Based on the Participant-Rated CGI of Improvement at Week 1 and Week 12 (End of Treatment)

"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Week 1 and Week 12

,,
Interventionparticipants (Number)
Responders at the End of Treatment (Week 12)Responders at the End of One Week
GEn (XP13512/GSK1838262) 1200 mg8352
GEn (XP13512/GSK1838262) 600 mg9055
Placebo4620

Number of Participants Classified as Responders With at Least 30% and 50% Improvement in the Average Daily RLS Pain Score Using LOCF

"The Mean Daily RLS pain was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined visits A Responder is a participant with a score of much improved or very much improved on the investigator rated CGI I Scale at the end of treatment (Week 12 using LOCF)." (NCT00365352)
Timeframe: Week 12

,,
Interventionparticipants (Number)
> or equal to 30% response> or equal to 50% response
GEn (XP13512/GSK1838262) 1200 mg7666
GEn (XP13512/GSK1838262) 600 mg7562
Placebo4841

Number of Participants Experiencing No RLS Symptoms in Each of the Seven 4-hour Periods From the 24-hour RLS Record at Week 12 (End of Treatment)

RLS severity ratings were summarized in 6 non-overlapping 4-hour periods beginning at 8 AM. A 4-hour period from 6 PM to 10 PM was also prospectively included to reflect the time frame when the most participants would experience their first symptoms of the day. (NCT00365352)
Timeframe: Week 12

,,
Interventionparticipants (Number)
8 AM to 12 PM12 PM to 4 PM4 PM to 8 PM6 PM to 10 PM8 PM to 12 AM12 AM to 4 AM4 AM to 8 AM
GEn (XP13512/GSK1838262) 1200 mg74696155486772
GEn (XP13512/GSK1838262) 600 mg85746855497479
Placebo52514539273856

Reviews

4 reviews available for carbamates and Fatigue

ArticleYear
Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis.
    Acta neurologica Scandinavica, 2021, Volume: 144, Issue:1

    Topics: Anticonvulsants; Carbamates; Chlorophenols; Dizziness; Dose-Response Relationship, Drug; Drug Resist

2021
Sofosbuvir/Velpatasvir for the treatment of Hepatitis C Virus infection.
    Acta bio-medica : Atenei Parmensis, 2018, 10-08, Volume: 89, Issue:3

    Topics: Adult; Antiviral Agents; Carbamates; Clinical Trials as Topic; Drug Therapy, Combination; Fatigue; F

2018
Elbasvir/grazoprevir (Zepatier) for hepatitis C.
    The Medical letter on drugs and therapeutics, 2016, Feb-29, Volume: 58, Issue:1489

    Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Clinical Trials as Topic; Cyclopropanes; Drug Com

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016
Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials.
    Clinical therapeutics, 2016, Volume: 38, Issue:7

    Topics: Carbamates; Dizziness; Double-Blind Method; Fatigue; gamma-Aminobutyric Acid; Humans; Randomized Con

2016

Trials

5 trials available for carbamates and Fatigue

ArticleYear
Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial.
    Journal of viral hepatitis, 2022, Volume: 29, Issue:9

    Topics: Amides; Antiviral Agents; Benzimidazoles; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Comb

2022
Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
    European journal of cancer (Oxford, England : 1990), 2019, Volume: 119

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Fatigue; Female; Humans;

2019
Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study.
    European journal of gastroenterology & hepatology, 2018, Volume: 30, Issue:10

    Topics: 2-Naphthylamine; Adult; Anemia; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropane

2018
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
    Annals of internal medicine, 2015, Jul-07, Volume: 163, Issue:1

    Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes;

2015
Safety and efficacy of ezogabine (retigabine) in adults with refractory partial-onset seizures: Interim results from two ongoing open-label studies.
    Epilepsy research, 2012, Volume: 102, Issue:1-2

    Topics: Adult; Anticonvulsants; Carbamates; Dizziness; Drug Resistance; Epilepsies, Partial; Fatigue; Female

2012

Other Studies

8 other studies available for carbamates and Fatigue

ArticleYear
Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.
    Pharmacoepidemiology and drug safety, 2019, Volume: 28, Issue:12

    Topics: Adult; Aged; Aged, 80 and over; Anemia; Antiviral Agents; Brazil; Carbamates; Drug Therapy, Combinat

2019
Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient.
    Renal failure, 2020, Volume: 42, Issue:1

    Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combination; Fatigue

2020
An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection.
    Clinical and molecular hepatology, 2019, Volume: 25, Issue:4

    Topics: Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Clinical Trials, Phase III as Topic;

2019
The combination of daclatasvir and sofosbuvir for curing genotype 2 patients who cannot tolerate ribavirin.
    Liver international : official journal of the International Association for the Study of the Liver, 2016, Volume: 36, Issue:7

    Topics: Aged; Antiviral Agents; Carbamates; Drug Administration Schedule; Drug Therapy, Combination; Fatigue

2016
Interferon/Ribavirin-Free Antiviral Treatment in Septuagenarians and Octogenarians With Chronic Hepatitis C.
    The American journal of gastroenterology, 2016, Volume: 111, Issue:5

    Topics: Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Carbamates; Drug Therapy, Combination; Fa

2016
Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study.
    Medicine, 2016, Volume: 95, Issue:27

    Topics: Antiviral Agents; Austria; Benzimidazoles; Carbamates; Coinfection; Fatigue; Female; Fluorenes; Hepa

2016
Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis.
    Canadian journal of gastroenterology & hepatology, 2017, Volume: 2017

    Topics: Amides; Antiviral Agents; Asthenia; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combinatio

2017
Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine.
    British journal of clinical pharmacology, 2010, Volume: 69, Issue:5

    Topics: Adolescent; Adult; Biological Transport; Carbamates; Cimetidine; Constipation; Dose-Response Relatio

2010