Page last updated: 2024-10-16

carbamates and Emesis

carbamates has been researched along with Emesis in 17 studies

Research Excerpts

ExcerptRelevanceReference
"In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300)."9.34Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D, 2020)
"The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat."7.74Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat. ( Cross-Mellor, SK; Ossenkopp, KP; Parker, LA; Piomelli, D, 2007)
"In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300)."5.34Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D, 2020)
"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)
"Encorafenib (Braftovi) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi)."4.02Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report. ( Lankheet, NAG; Meussen, E; Mian, P; Piersma, D, 2021)
"We evaluated the effectiveness of the potent selective monoacylglycerol lipase (MAGL) inhibitor, MJN110, which selectively elevates the endocannabinoid 2-AG, to suppress acute nausea and vomiting, as well as anticipatory nausea in rat and shrew models."3.81Effect of selective inhibition of monoacylglycerol lipase (MAGL) on acute nausea, anticipatory nausea, and vomiting in rats and Suncus murinus. ( Abdullah, RA; Cravatt, BF; Downey, R; Lichtman, AH; Limebeer, CL; Morris, H; Niphakis, MJ; Parker, LA; Rock, EM; Sticht, MA, 2015)
"The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat."3.74Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat. ( Cross-Mellor, SK; Ossenkopp, KP; Parker, LA; Piomelli, D, 2007)
"In human volunteers, studies to assess the adverse effects of the carbamate anticholinesterase physostigmine showed that the intramuscular dose observed to induce emesis in 50% of subjects tested (ED50) was 28."3.68A model for carbamate and organophosphate-induced emesis in humans. ( D'Mello, GD; Sidell, FR, 1991)
"CNS excitation and seizures, manifestations of organochlorine intoxication, can occur following ingestion or inappropriate application of the 1 per cent topical formulation of lindane used to treat scabies and lice."2.37Management of acute childhood poisonings caused by selected insecticides and herbicides. ( Mortensen, ML, 1986)
"The administration of emetic agents in dogs for the purpose of gastric decontamination is not without risk, although the incidence of adverse effects is unknown and likely under-reported."1.51Side effects of powdered sodium carbonate (washing or 'Lectric' soda) used as an oral emetic agent in five dogs. ( Indrawirawan, YH; Watson, AK, 2019)
"Acute pancreatitis was diagnosed in 5 subjects."1.28Acute pancreatitis in children with anticholinesterase insecticide intoxication. ( Sofer, S; Weizman, Z, 1992)

Research

Studies (17)

TimeframeStudies, this research(%)All Research%
pre-19905 (29.41)18.7374
1990's2 (11.76)18.2507
2000's3 (17.65)29.6817
2010's5 (29.41)24.3611
2020's2 (11.76)2.80

Authors

AuthorsStudies
Gogas, HJ2
Flaherty, KT2
Dummer, R2
Ascierto, PA2
Arance, A2
Mandala, M2
Liszkay, G2
Garbe, C2
Schadendorf, D2
Krajsova, I2
Gutzmer, R2
Sileni, VC1
Dutriaux, C1
de Groot, JWB2
Yamazaki, N1
Loquai, C2
Gollerkeri, A2
Pickard, MD2
Robert, C2
Mian, P1
Meussen, E1
Piersma, D1
Lankheet, NAG1
Watson, AK1
Indrawirawan, YH1
Parker, LA3
Niphakis, MJ1
Downey, R1
Limebeer, CL2
Rock, EM2
Sticht, MA1
Morris, H1
Abdullah, RA1
Lichtman, AH1
Cravatt, BF1
Tongpoo, A1
Sriapha, C1
Wongvisawakorn, S1
Rittilert, P1
Trakulsrichai, S1
Wananukul, W1
Litt, DL1
Kwiatkowska, M1
Piomelli, D2
Percie du Sert, N1
Ho, WS1
Rudd, JA1
Andrews, PL1
Darmani, NA1
McClanahan, BA1
Trinh, C1
Petrosino, S1
Valenti, M1
Di Marzo, V1
Cross-Mellor, SK1
Ossenkopp, KP1
Weizman, Z1
Sofer, S1
D'Mello, GD1
Sidell, FR1
Mortensen, ML1
Gailani, S1
Blais, M1
Udall, ND1
Müntzing, J1
Shukla, SK1
Chu, TM1
Mittelman, A1
Murphy, GP1
Luce, JK1
Bodey, GP1

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
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
A Phase 1B Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Combination of Encorafenib, Binimetinib and Palbociclib in Patients With BRAF-mutant Metastatic Melanoma (The CELEBRATE Study)[NCT04720768]Phase 1/Phase 278 participants (Anticipated)Interventional2020-06-04Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

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

Reviews

1 review available for carbamates and Emesis

ArticleYear
Management of acute childhood poisonings caused by selected insecticides and herbicides.
    Pediatric clinics of North America, 1986, Volume: 33, Issue:2

    Topics: Absorption; Adolescent; Animals; Anticonvulsants; Atropine; Carbamates; Central Nervous System; Chil

1986

Trials

4 trials available for carbamates and Emesis

ArticleYear
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
Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma.
    European journal of cancer (Oxford, England : 1990), 2020, Volume: 126

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carb

2020
Clinical trial of acetylenic carbamate: 1,1-diphenyl-2-propynyl cyclohexanecarbamate (NSC-112682).
    Cancer chemotherapy reports, 1970, Volume: 54, Issue:3

    Topics: Adolescent; Adult; Aged; Alkynes; Antineoplastic Agents; Carbamates; Carcinoma, Bronchogenic; Carcin

1970
Initial clinical trials with 1,1-diphenyl-2-propynyl cyclohexanecarbamate (NCS-112682).
    Cancer chemotherapy reports, 1970, Volume: 54, Issue:2

    Topics: Alkynes; Antineoplastic Agents; Bone Marrow; Carbamates; Clinical Trials as Topic; Cyclohexanes; Eva

1970

Other Studies

12 other studies available for carbamates and Emesis

ArticleYear
Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report.
    Anti-cancer drugs, 2021, 06-01, Volume: 32, Issue:5

    Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; C

2021
Side effects of powdered sodium carbonate (washing or 'Lectric' soda) used as an oral emetic agent in five dogs.
    Australian veterinary journal, 2019, Volume: 97, Issue:5

    Topics: Animals; Carbamates; Dog Diseases; Dogs; Emetics; Fatal Outcome; Female; Male; Powders; Vomiting

2019
Effect of selective inhibition of monoacylglycerol lipase (MAGL) on acute nausea, anticipatory nausea, and vomiting in rats and Suncus murinus.
    Psychopharmacology, 2015, Volume: 232, Issue:3

    Topics: Animals; Carbamates; Disease Models, Animal; Female; Male; Monoacylglycerol Lipases; Nausea; Rats; R

2015
OCCUPATIONAL CARBAMATE POISONING IN THAILAND.
    The Southeast Asian journal of tropical medicine and public health, 2015, Volume: 46, Issue:4

    Topics: Adolescent; Adult; Aged; Agricultural Workers' Diseases; Carbamates; Carbofuran; Child; Diarrhea; Fe

2015
The FAAH inhibitor URB-597 interferes with cisplatin- and nicotine-induced vomiting in the Suncus murinus (house musk shrew).
    Physiology & behavior, 2009, Apr-20, Volume: 97, Issue:1

    Topics: Amidohydrolases; Animals; Arachidonic Acids; Benzamides; Carbamates; Cisplatin; Drug Interactions; E

2009
Cannabinoid-induced reduction in antral pacemaker frequency: a telemetric study in the ferret.
    Neurogastroenterology and motility, 2010, Volume: 22, Issue:11

    Topics: Amidohydrolases; Animals; Apomorphine; Benzamides; Biological Clocks; Body Temperature; Cannabinoids

2010
Cisplatin increases brain 2-arachidonoylglycerol (2-AG) and concomitantly reduces intestinal 2-AG and anandamide levels in the least shrew.
    Neuropharmacology, 2005, Volume: 49, Issue:4

    Topics: Analysis of Variance; Animals; Apomorphine; Arachidonic Acids; Benzamides; Benzyl Compounds; Brain;

2005
Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat.
    Psychopharmacology, 2007, Volume: 190, Issue:2

    Topics: Amidohydrolases; Animals; Arachidonic Acids; Association Learning; Avoidance Learning; Benzamides; C

2007
Acute pancreatitis in children with anticholinesterase insecticide intoxication.
    Pediatrics, 1992, Volume: 90, Issue:2 Pt 1

    Topics: Abdominal Pain; Acute Disease; Amylases; Blood Glucose; Butyrylcholinesterase; Carbamates; Child; Ch

1992
A model for carbamate and organophosphate-induced emesis in humans.
    Neuroscience and biobehavioral reviews, 1991,Spring, Volume: 15, Issue:1

    Topics: Adolescent; Adult; Animals; Atropine; Behavior, Animal; Callitrichinae; Carbamates; Cholinesterases;

1991
The toxicity of the molluscicides metaldehyde and methiocarb to dogs.
    The Veterinary record, 1973, Oct-13, Volume: 93, Issue:15

    Topics: Acetaldehyde; Animals; Atropine; Carbamates; Dog Diseases; Dogs; Gluconates; Glucose; Hyperemia; Kid

1973
Pharmacoclinical study of oral estramustine phosphate (Estracyt) in advanced carcinoma of the prostate.
    Investigative urology, 1974, Volume: 12, Issue:1

    Topics: Acid Phosphatase; Administration, Oral; Antineoplastic Agents; Carbamates; Carcinoembryonic Antigen;

1974