A Phase II Study of Single Agent MEK162 in Patients With... | NCT01320085

ID	Type	Description	Link
C4211001	Other Identifier	Alias Study Number
2010-023412-13	EudraCT Number

Label	Type	Description	Intervention Names
BRAFV600 mutant, 45mg bid MEK162	Experimental	BRAFV600 mutant, 45mg bid MEK162	Drug: MEK162
NRAS mutant, 45mg bid MEK162	Experimental	NRAS mutant, 45mg bid MEK162	Drug: MEK162
BRAFV600 mutant, 60mg bid MEK162	Experimental	BRAFV600 mutant, 60mg bid MEK162	Drug: MEK162

Name	Type	Description	Arm Group Labels	Other Names
MEK162	Drug		BRAFV600 mutant, 45mg bid MEK162 BRAFV600 mutant, 60mg bid MEK162 NRAS mutant, 45mg bid MEK162

Measure	Description	Time Frame
Percentage of Participants With Objective Response (OR)	Objective response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.0, was defined as participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.	From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause, whichever occurred first (maximum duration of up to 33 months)

Measure	Description	Time Frame
Progression-Free Survival (PFS)	PFS as assessed by investigator per RECIST v1.0, was defined as time (in months) from date of randomization or date of start of treatment to first documentation of PD or date of death due to any cause or data censoring date, whichever occurred first. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of greater than or equal to (>=) 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. If a participant did not had an event, data censoring was done at the date of last adequate tumor assessment. Analysis was performed using Kaplan-Meier method.

Name	Affiliation	Role
Pfizer Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Highlands Oncology Group		Fayetteville	Arkansas	72703-4005	United States
H. Lee Moffitt Cancer Center & Research Institute, Inc.

PubMed Identifier	Type	Citation	Retractions
23414587	Derived	Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. doi: 10.1016/S1470-2045(13)70024-X. Epub 2013 Feb 13.

ID	Title	Description
FG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Objective Response (OR)

Objective response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.0, was defined as participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.

The full analysis set included all randomized participants who received at least one dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause, whichever occurred first (maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF	Participants with BRAF mutations received an oral dose of 60 mg of binimetinib (4 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Units	Counts
Participants	OG00041 OG001117 OG00225

Title

Denominators

Categories

Title	Measurements
	OG0004.9(0.6 to 16.5) OG00114.5(8.7 to 22.2) OG00212.0(2.5 to 31.2)

Secondary

Progression-Free Survival (PFS)

PFS as assessed by investigator per RECIST v1.0, was defined as time (in months) from date of randomization or date of start of treatment to first documentation of PD or date of death due to any cause or data censoring date, whichever occurred first. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of greater than or equal to (>=) 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. If a participant did not had an event, data censoring was done at the date of last adequate tumor assessment. Analysis was performed using Kaplan-Meier method.

The full analysis set included all randomized participants who received at least one dose of study drug.

Posted

Median

95% Confidence Interval

months

From date of randomization or date of start of treatment until date of first documentation of PD or date of death due to any cause or date of data censoring, whichever occurred first (maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Overall Survival (OS)

Overall survival was defined as the time (in months) from the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

The full analysis set included all randomized participants who received at least one dose of study drug.

Posted

Median

95% Confidence Interval

months

From date of randomization or date of start of treatment to date of death due to any cause or date of censoring, whichever occurred first (maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Duration of Response (DOR)

DOR:time from first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause/data censoring date,whichever occurred first. As per RECIST v1.0, CR:disappearance of all target(T) and non-target (Non-T) lesions sustained for =>4 weeks. Any pathological lymph nodes(T or non-T) reduced in short axis to <10mm. PR:>=30% decrease in sum of diameters(SOD) of T lesions, taking as reference baseline SOD. PD for T lesions:at least a 20% increase in sum of diameters of T lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm,or appearance of >=1 new lesions.PD for Non-T lesions:unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy/appearance of new unequivocal malignant lesion.Data was censored on date of last adequate tumor assessment for participants without an event,who started new anti-cancer treatment prior to assessment,who missed >=2 tumor assessments.

The full analysis set included all randomized participants who received at least one dose of study drug. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

months

From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Time to Response (TTR)

TTR as assessed by investigator according to RECIST v1.0, was defined as the time (in months) from date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival.

Posted

Median

95% Confidence Interval

months

From the date of randomization or date of start of treatment to the first documentation of objective response (CR or PR) or data censoring date, whichever occurred first (maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Reactions Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.0

Adverse drug reaction (ADR) was any untoward medical occurrence attributed to study drug in participants who received study drug. As per NCI-CTCAE v4.0, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or non-invasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to study drug. Treatment-emergent ADRs are between first dose of study drug and up to 30 days after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. Number of participants with any Grade 3 or 4 treatment-emergent ADR were reported in this outcome measure.

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Serious Adverse Reactions

A serious ADR was an ADR resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying) ; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly, important medical event.

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

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

Hematology per NCI-CTCAE included, Lymphocyte count decreased-(G1:<0.8, G2:<0.8-0.5, G3:<0.5-0.2, G4:<0.2[*10^9/L]); Lymphocyte count increased-(G2:>4-20, G3:>20[*10^9/L]); Neutrophil count decreased-(G1:<1.5, G2:<1.5-1.0, G3:<1.0-0.5, G4:<0.5[*10^9/L]); Activated partial thromboplastin time prolonged (seconds)-(G1:>1.5*upper limit normal (ULN), G2:>1.5-2.5*ULN, G3:>2.5*ULN); Platelet count decreased-(G1:<75.0, G2:<75.0-50.0, G3:<50.0-25.0, G4:<25.0[*10^9/L]); Fibrinogen decreased-(G1:<1.0-0.75*lower limit normal (LLN), G2:<0.75-0.5*LLN, G3:<0.5-0.25*LLN G4:<0.25*LLN); Anemia-(G1:<LLN-100, G2:<100-80, G3:<80 [g/L], G4:Life-threatening, G5:death); Hemoglobin increased-(G1:>0-2 g/dL above ULN, G2:>2-4 g/dL above ULN, G3:>4 g/dL above ULN); Prothrombin time (INR) increased-(G1:>1-1.5, G2:>1.5-2.5, G3:>2.5[*ULN]); WBC decreased-(G1:<3.0*10^9/L, G2:<3.0-2.0*10^9/L, G3:<2.0-1.0*10^9/L, G4:<1.0*10^9/L); WBC increased-(G3:>100,000/mm3, G4:Clinical manifestations of increase in WBC, G5:death).

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

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

Albumin(G1:<30,G2:<30-20,G3:<20[g/L], G4:life-threatening, G5:death);Alkaline phosphatase(G1:>2.5,G2:>2.5-5.0,G3:>5.0-20.0, G4:>20.0[*ULN]);Creatine kinase(G1:>2.5,G2:>2.5-5,G3:>5-10,G4:>10[*ULN]);Creatinine(CT) clearance(G1:<LLN-60,G2:59-30,G3:29-15,G3:<15[ml/min/1.73m^2], G5:death);CT (G1:>1.5,G2:>1.5-3.0,G3:>3.0-6.0,G4:>6.0[*ULN]);Hypomagnesemia(G1:<0.5,G2:<0.5-0.4,G3:<0.4-0.3,G4:<0.3[mmol/L],G5:death);Hypermagnesemia(G1:>1.23,G3:>1.23-3.30, G4:>3.30[mmol/L],G5:death);Hypophosphatemia(G1:<0.8,G2:<0.8-0.6,G3:<0.6-0.3,G4:<0.3[mmol/L], G5:death);Hypokalemia(G1:<3.0,G2:<3.0,G3:<3.0-2.5,G4:<2.5[mmol/L],G5:death);Hyperkalemia(G1:>5.5,G2:>5.5-6.0,G3:>6.0-7.0, G4:>7.0[mmol/L],G5:death);AST(G1:>3.0,G2:>3.0-5.0,G3:>5.0-20.0,G4:>20.0[*ULN]); ALT(G1:>3.0,G2:>3.0-5.0,G3:>5.0-20.0,G4:>20.0[*ULN]);Hyponatremia(G1:<130,G3:<130-120,G4:<120[mmol/L],G5:death);Hypernatremia(G1:150,G2:>150-155,G3:>155-160,G4:>160[mmol/L],G5:death);High blood bilirubin (G1:>1.5,G2:>1.5-3.0,G3:>3.0-10.0,G4:>10.0[*ULN]).

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Shift From Baseline in Vital Signs Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Blood Pressure)

Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP).

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate

Pre-defined criteria of markedly abnormal vital signs abnormalities was defined as increase or decrease from baseline (>=15 beats per minute) in pulse rate of >=120 beats per minute or less than or equal to (<=) 50 beats per minute.

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Markedly Abnormal Vital Sign Values: Weight

Vital signs included assessment of body weight. Body weight (in kilograms) measurements included high and low. Pre-defined criteria of markedly abnormal vital signs abnormalities was defined as increase or decrease from baseline in weight of >=10%.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Notable Electrocardiogram (ECG) Values

ECG findings included maximum value of >450 millisecond (msec), >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval corrected using Fridericia's formula (QTcF); maximum value of >450 msec, >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval corrected using Bazett's formula (QTcB); maximum value of >450 msec, >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval; RR decrease >25% and to a VR >100, RR increase >25% and to a VR <50 beats per minute for VR interval; an increase >25% and to a value >200 msec for PR interval; an increase >25% and to a value >110 msec for QRS interval.

Safety analysis set included all participants who had received at least one dose of study drug and had at least one valid post-baseline safety assessment. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy

Fundoscopy examination included an examination of the retina, vitreous, macula, optic nerve, optic nerve pallor, choroid and other new abnormalities in either or both eyes. New abnormalities were identified where the baseline assessment showed no abnormalities in a particular eye, but at the post-dose time point an abnormality was observed. New abnormalities at any time point were reported and included unscheduled assessments.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination

Slit lamp examination included an examination of the conjunctiva, cornea, iris, lens, anterior chamber, lids and other new abnormalities in either or both eyes. New abnormalities were identified where the baseline assessment showed no abnormalities in a particular eye, but at the post-dose time point an abnormality was observed. New abnormalities at any time point were reported and included unscheduled assessments.

Posted

Count of Participants

Participants

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib

Pharmacokinetic (PK) analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002

Secondary

Maximum Plasma Concentration (Cmax) of Binimetinib

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Median

Full Range

hours

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Median

Full Range

hours

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Trough Plasma Concentration (Ctrough) of Binimetinib

Ctrough refers to plasma concentration of Binimetinib observed just before treatment administration.

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here "Overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

Pre-dose (0 hour) on Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Apparent Total Body Clearance (CL/F) of Binimetinib

Drug clearance was defined as a quantitative measure of the rate at which a drug substance was removed from the plasma. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter/hour

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Median

Full Range

hours

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*nanogram per milliliter

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002

Secondary

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite

PK analysis set included all participants who had at least one blood sample providing evaluable PK data. Here 'number analyzed' signifies participants with available data for each specified category.

Posted

Median

Full Range

hours

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG002	Binimetinib 60 mg BRAF

Secondary

Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite

Ctrough refers to plasma concentration of Binimetinib's metabolite observed just before treatment administration.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

Pre-dose (0 hour) on Day 15 of Cycle 1

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Percent Change From Baseline in Histological Score (H-score) for Phosphorylated Extracellular Signal-Regulated Kinase (pERK) From Tumor Samples of Cytoplasmic and Nuclear Cellular Compartment

Percent change from baseline in H-score for pERK from tumor samples was assessed and summarized. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.

Posted

Mean

Standard Deviation

percent change

Baseline up to maximum duration of up to 33 months

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Secondary

Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples

The percentage change in DUSP6 gene expression was derived from the Relative Expression Ratio (RER) computed via the Delta Ct method. DUSP6, a protein coding gene was used as a biomarker of inhibition of the mitogen-activated protein kinase (MEK) pathway.

Posted

Mean

Standard Deviation

percent change

Baseline up to maximum duration of up to 33 months

ID	Title	Description
OG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
OG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0004 affected41 at risk EG00117 affected117 at risk EG0023 affected25 at risk
Chorioretinopathy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG00116 affected117 at risk EG0021 affected25 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG00018 affected41 at risk EG00157 affected117 at risk EG00213 affected25 at risk
Nausea	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG00010 affected41 at risk EG00137 affected117 at risk EG00212 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0004 affected41 at risk EG00121 affected117 at risk EG00210 affected25 at risk
Constipation	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG00123 affected117 at risk EG0024 affected25 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG00113 affected117 at risk EG0025 affected25 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0019 affected117 at risk EG0021 affected25 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0017 affected117 at risk EG0023 affected25 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0019 affected117 at risk EG0021 affected25 at risk
Oedema peripheral	General disorders	MedDRA v18.1	Non-systematic Assessment	EG00017 affected41 at risk EG00160 affected117 at risk EG00214 affected25 at risk
Fatigue	General disorders	MedDRA v18.1	Non-systematic Assessment	EG00012 affected41 at risk EG00140 affected117 at risk EG00212 affected25 at risk
Pyrexia	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0005 affected41 at risk EG00118 affected117 at risk EG0022 affected25 at risk
Face oedema	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0005 affected41 at risk EG00111 affected117 at risk EG0025 affected25 at risk
Asthenia	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG00110 affected117 at risk EG0020 affected25 at risk
Rash pustular	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG00111 affected117 at risk EG0022 affected25 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG00012 affected41 at risk EG00160 affected117 at risk EG00214 affected25 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG00120 affected117 at risk EG0022 affected25 at risk
Alanine aminotransferase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG00118 affected117 at risk EG0022 affected25 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG00110 affected117 at risk EG0023 affected25 at risk
Ejection fraction decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG00110 affected117 at risk EG0021 affected25 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0005 affected41 at risk EG00119 affected117 at risk EG0023 affected25 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0019 affected117 at risk EG0027 affected25 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG00113 affected117 at risk EG0024 affected25 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG00114 affected117 at risk EG0022 affected25 at risk
Dysgeusia	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0009 affected41 at risk EG0018 affected117 at risk EG0021 affected25 at risk
Headache	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0017 affected117 at risk EG0024 affected25 at risk
Dizziness	Nervous system disorders	MedDRA v17.0	Non-systematic Assessment	EG0003 affected41 at risk EG0016 affected117 at risk EG0024 affected25 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG00111 affected117 at risk EG0021 affected25 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0005 affected41 at risk EG0015 affected117 at risk EG0021 affected25 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG00015 affected41 at risk EG00164 affected117 at risk EG0028 affected25 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG00016 affected41 at risk EG00125 affected117 at risk EG0025 affected25 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0004 affected41 at risk EG00121 affected117 at risk EG0023 affected25 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG00118 affected117 at risk EG0025 affected25 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG00115 affected117 at risk EG0022 affected25 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0004 affected41 at risk EG0018 affected117 at risk EG0023 affected25 at risk
Hypertension	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG00125 affected117 at risk EG0026 affected25 at risk
Weight decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0018 affected117 at risk EG0020 affected25 at risk
Visual field defect	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0018 affected117 at risk EG0021 affected25 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0016 affected117 at risk EG0023 affected25 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Lymph node pain	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Normochromic normocytic anaemia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Angina pectoris	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Arrhythmia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Bundle branch block right	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Defect conduction intraventricular	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hypertensive cardiomyopathy	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Palpitations	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Sinus bradycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Sinus tachycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Tachycardia	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Cleft lip	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Colour blindness	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Congenital cleft hand	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Congenital optic nerve anomaly	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Corneal dystrophy	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Corneal opacity congenital	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Dermoid cyst	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Macular dystrophy congenital	Congenital, familial and genetic disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Ear pain	Ear and labyrinth disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Ear swelling	Ear and labyrinth disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Vertigo	Ear and labyrinth disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Hypothyroidism	Endocrine disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Amblyopia	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Blepharitis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0021 affected25 at risk
Blepharospasm	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Cataract	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Conjunctival irritation	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Conjunctival oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Conjunctivitis allergic	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Conjunctivochalasis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Corneal disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Corneal scar	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Detachment of macular retinal pigment epithelium	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Detachment of retinal pigment epithelium	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0018 affected117 at risk EG0020 affected25 at risk
Diplopia	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Dry eye	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0023 affected25 at risk
Eczema eyelids	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Extraocular muscle paresis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye allergy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye colour change	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye degenerative disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye discharge	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye irritation	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye movement disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye pain	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Eye swelling	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Eyelid disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eyelid oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0016 affected117 at risk EG0021 affected25 at risk
Glaucoma	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Lacrimation increased	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Lenticular opacities	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Macular degeneration	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Macular oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Maculopathy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Meibomianitis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Ocular discomfort	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Ocular hypertension	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Ocular vascular disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Optic disc haemorrhage	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Optic nerve disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Orbital oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Papilloedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Paraneoplastic retinopathy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Periorbital oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG00110 affected117 at risk EG0024 affected25 at risk
Photophobia	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Photopsia	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Posterior capsule opacification	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Punctate keratitis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Retinal cyst	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Retinal detachment	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Retinal disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0023 affected25 at risk
Retinal exudates	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Retinal haemorrhage	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Retinal oedema	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Retinal pigment epitheliopathy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0021 affected25 at risk
Retinal vein occlusion	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Retinopathy	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG00112 affected117 at risk EG0029 affected25 at risk
Retinoschisis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Subretinal fluid	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0018 affected117 at risk EG0021 affected25 at risk
Trichiasis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Ulcerative keratitis	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Vision blurred	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0017 affected117 at risk EG0021 affected25 at risk
Visual acuity reduced	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Visual impairment	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Vitreous detachment	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Vitreous disorder	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Vitreous floaters	Eye disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Anal haemorrhage	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Anal inflammation	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Aphthous ulcer	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0022 affected25 at risk
Ascites	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Cheilitis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Dry mouth	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0015 affected117 at risk EG0021 affected25 at risk
Dysphagia	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Eructation	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Faecal incontinence	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Faeces soft	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Flatulence	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0024 affected25 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Gastritis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Glossodynia	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Haematemesis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Haematochezia	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Intussusception	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Lip dry	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Oral discomfort	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Oral mucosal erythema	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rectal obstruction	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Regurgitation	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Swollen tongue	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Tongue discolouration	Gastrointestinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Axillary pain	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Chest pain	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Chills	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0015 affected117 at risk EG0022 affected25 at risk
Facial pain	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Feeling cold	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Gait disturbance	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
General physical health deterioration	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Granuloma	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Hypothermia	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Inflammation	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Influenza like illness	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Localised oedema	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Malaise	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Mucosal dryness	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Mucosal inflammation	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Mucous membrane disorder	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Non-cardiac chest pain	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Oedema	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0022 affected25 at risk
Pain	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Performance status decreased	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Peripheral swelling	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Swelling	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Ulcer	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Xerosis	General disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0015 affected117 at risk EG0021 affected25 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Allergy to vaccine	Immune system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Angular cheilitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Bacteraemia	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Body tinea	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Bronchitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Candida infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Cellulitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0022 affected25 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Conjunctivitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Conjunctivitis bacterial	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Corona virus infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Cystitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0021 affected25 at risk
Erysipelas	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0014 affected117 at risk EG0022 affected25 at risk
Escherichia infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Folliculitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Gastroenteritis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Gastrointestinal infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Gingivitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Hordeolum	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0023 affected25 at risk
Influenza	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Lip infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Lung infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Lymphangitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Nasopharyngitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Oral candidiasis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Oral herpes	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Orchitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Paronychia	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Pharyngitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pneumonia	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Post procedural infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pulpitis dental	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Rhinitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Sinusitis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Skin infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Soft tissue infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Tinea pedis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Urinary tract infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Viral infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Wound infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Anal injury	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Injury	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Ligament injury	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Wound	Injury, poisoning and procedural complications	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Amylase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Blood albumin increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Blood bilirubin increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Blood creatine phosphokinase MB increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Blood creatinine increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0016 affected117 at risk EG0022 affected25 at risk
Blood fibrinogen increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0022 affected25 at risk
Blood magnesium decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Blood phosphorus decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Blood phosphorus increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Blood potassium decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Blood potassium increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Blood pressure increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Blood sodium decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Blood thyroid stimulating hormone decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Blood urea increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Blood urine present	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
C-reactive protein increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0015 affected117 at risk EG0020 affected25 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Electrocardiogram ST segment elevation	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Electrocardiogram T wave abnormal	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Fibrin D dimer increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0016 affected117 at risk EG0020 affected25 at risk
International normalised ratio increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Intraocular pressure increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0017 affected117 at risk EG0020 affected25 at risk
Lipase increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Lymphocyte count decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Platelet count decreased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Prothrombin time shortened	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Sinus rhythm	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Troponin T increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Weight increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0013 affected117 at risk EG0023 affected25 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0022 affected25 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0014 affected117 at risk EG0021 affected25 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0015 affected117 at risk EG0022 affected25 at risk
Bone swelling	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Lupus-like syndrome	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Muscle fatigue	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0018 affected117 at risk EG0020 affected25 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Sjogren's syndrome	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Adrenal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Blepharal papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eye naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pyogenic granuloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Disturbance in attention	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Dysaesthesia	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Dysarthria	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hemianopia homonymous	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Hypoaesthesia	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Hypotonia	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Loss of consciousness	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Migraine	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Neurological symptom	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Somnolence	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Syncope	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0023 affected25 at risk
Confusional state	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0022 affected25 at risk
Depression	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Hallucination	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Insomnia	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Mood swings	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Panic attack	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Schizophrenia, paranoid type	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Sleep disorder	Psychiatric disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Dysuria	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Haematuria	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Incontinence	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nocturia	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Obstructive uropathy	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Proteinuria	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Renal colic	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Renal failure	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Renal pain	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Urinary retention	Renal and urinary disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Penile oedema	Reproductive system and breast disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Scrotal oedema	Reproductive system and breast disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Vaginal inflammation	Reproductive system and breast disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Apnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0022 affected25 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nasal crusting	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Nasal discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nasal odour	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Painful respiration	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Pharyngeal ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rhinalgia	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Asteatosis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Chronic pigmented purpura	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Cutis laxa	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0021 affected25 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Eczema weeping	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Generalised erythema	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Hair growth abnormal	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Keloid scar	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Milia	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0014 affected117 at risk EG0020 affected25 at risk
Nail ridging	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0020 affected25 at risk
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Rash follicular	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0017 affected117 at risk EG0021 affected25 at risk
Rash maculovesicular	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0013 affected117 at risk EG0020 affected25 at risk
Rosacea	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Scab	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Skin erosion	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0017 affected117 at risk EG0022 affected25 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Skin maceration	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Skin plaque	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0021 affected25 at risk
Solar dermatitis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Stasis dermatitis	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Toxic skin eruption	Skin and subcutaneous tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Erythromelalgia	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Flushing	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0022 affected25 at risk
Haematoma	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Hyperanemia	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Hypotension	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0022 affected25 at risk
Lymphoedema	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0003 affected41 at risk EG0013 affected117 at risk EG0022 affected25 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Peripheral coldness	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Raynaud's phenomenon	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Thrombophlebitis	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0001 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Venous thrombosis	Vascular disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0012 affected117 at risk EG0020 affected25 at risk
Troponin increased	Investigations	MedDRA v18.1	Non-systematic Assessment	EG0002 affected41 at risk EG0011 affected117 at risk EG0020 affected25 at risk
Staphylococcal skin infection	Infections and infestations	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk
Memory impairment	Nervous system disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0011 affected117 at risk EG0021 affected25 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA v18.1	Non-systematic Assessment	EG0000 affected41 at risk EG0010 affected117 at risk EG0021 affected25 at risk

ID	Term
D009477	Hereditary Sensory and Autonomic Neuropathies
D008545	Melanoma

ID	Term
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D011115	Polyneuropathies
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Title	Description
BG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
BG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
BG002	Binimetinib 60 mg BRAF	Participants with BRAF mutations received an oral dose of 60 mg of binimetinib (4 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Binimetinib 45 mg BRAF	Participants with BRAF mutations received an oral dose of 45 milligrams (mg) of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.	5	41	11	41	40	41
EG001	Binimetinib 45 mg NRAS	Participants with NRAS mutations received an oral dose of 45 mg of binimetinib (3 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.	51	117	39	117	117	117
EG002	Binimetinib 60 mg BRAF	Participants with BRAF mutations received an oral dose of 60 mg of binimetinib (4 tablets each of 15 mg) twice daily, for each 28 days treatment cycle until development of unacceptable toxicity, disease progression, treatment discontinuation by participant refusal or investigator's decision whichever occurred first. Participants were followed up to 30 days after last dose of study drug.	10	25	9	25	25	25