Trial Outcomes & Findings for LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer (NCT NCT01685138)

Last Updated: 2019-03-26

Results Overview

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by the investigator. CR:Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Results posted on

2019-03-26

Participant Flow

Approximately 105 patients were planned to be enrolled. A total of 124 patients were enrolled and treated with ceritinib.

Participant milestones

Participant milestones
Measure	LDK378 (Ceritinib) Participants on this arm took oral LDK378 750 mg once daily.
Overall Study STARTED	124
Overall Study Discontinued From Treatment Phase	124
Overall Study Entered Post-treatment Efficacy f/up	10
Overall Study Entered Survival Follow-up	63
Overall Study Discontinued From Study	51
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	92

Reasons for withdrawal

Reasons for withdrawal
Measure	LDK378 (Ceritinib) Participants on this arm took oral LDK378 750 mg once daily.
Overall Study Lost to Follow-up	1
Overall Study Protocol Violation	1
Overall Study No longer requires treatment	1
Overall Study Subject/guardian decision	2
Overall Study Physician Decision	6
Overall Study Death	10
Overall Study Adverse Event	18
Overall Study Progressive disease	53

Baseline Characteristics

LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
Age, Continuous	54.8 Years STANDARD_DEVIATION 12.16 • n=99 Participants
Sex: Female, Male Female	74 Participants n=99 Participants
Sex: Female, Male Male	50 Participants n=99 Participants
Race/Ethnicity, Customized Asian	74 Participants n=99 Participants
Race/Ethnicity, Customized Caucasian	48 Participants n=99 Participants
Race/Ethnicity, Customized Black	1 Participants n=99 Participants
Race/Ethnicity, Customized Other	1 Participants n=99 Participants

PRIMARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
Overall Response Rate (ORR) by Investigator Assessment	67.7 Percentage of participants Interval 58.8 to 75.9

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
ORR by Blinded Independent Review Committee (BIRC)	63.7 Percentage of participants Interval 54.6 to 72.2

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) by investigator.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by investigator assessment per RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=84 Participants Participants on this arm took oral LDK378 750 mg once daily.
Duration of Response (DOR) as Per Investigator	24.0 Months Interval 14.8 to 37.5

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) as assessed by BIRC.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=79 Participants Participants on this arm took oral LDK378 750 mg once daily.
Duration of Response (DOR) as Per BIRC	27.3 Months Interval 16.6 to 44.3

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions that would qualify for PD. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
Disease Control Rate (DCR) as Per Investigator and BIRC DCR per Investigator	90.3 Percentage of participants Interval 83.7 to 94.9
Disease Control Rate (DCR) as Per Investigator and BIRC DCR per BIRC	86.3 Percentage of participants Interval 79.0 to 91.8

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug

Population: The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) by investigator.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=84 Participants Participants on this arm took oral LDK378 750 mg once daily.
Time to Response (TTR) as Per Investigator	2.5 Months Standard Deviation 2.66

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) as assessed by BIRC.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=79 Participants Participants on this arm took oral LDK378 750 mg once daily.
Time to Response (TTR) as Per BIRC	2.2 Months Standard Deviation 1.22

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by investigator.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by investigator.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=10 Participants Participants on this arm took oral LDK378 750 mg once daily.
Overall Intracranial Response Rate (OIRR) as Per Investigator	20.0 Percentage of participants Interval 2.5 to 55.6

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by BIRC.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by BIRC.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=13 Participants Participants on this arm took oral LDK378 750 mg once daily.
Overall Intracranial Response Rate (OIRR) as Per BIRC	61.5 Percentage of participants Interval 31.6 to 86.1

SECONDARY outcome

Timeframe: every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
Progression-free Survival (PFS) Per Investigator and BIRC PFS per Investigator	16.6 Months Interval 11.0 to 23.2
Progression-free Survival (PFS) Per Investigator and BIRC PFS per BIRC	19.4 Months Interval 10.9 to 29.3

SECONDARY outcome

Timeframe: Time from the date of first dose of LDK378 to the date of death due to any cause up to 5 years

Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

OS, defined as time from first dose of LDK378 to death due to any cause

Outcome measures

Outcome measures
Measure	LDK378 (Ceritinib) n=124 Participants Participants on this arm took oral LDK378 750 mg once daily.
Overall Survival (OS)	51.3 Months Interval 42.7 to 55.3

Adverse Events

LDK378 Ceritinib)

Serious events: 50 serious events

Other events: 123 other events

Deaths: 56 deaths

Serious adverse events

Serious adverse events
Measure	LDK378 Ceritinib) n=124 participants at risk Participants on this arm took oral LDK378 750 mg once daily.
Nervous system disorders Seizure	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Psychiatric disorders Depression	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 3/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Radicular pain	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Blood and lymphatic system disorders Neutropenia	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Cardiac disorders Cardiac tamponade	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Cardiac disorders Pericardial effusion	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Cardiac disorders Pericarditis	3.2% 4/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Congenital, familial and genetic disorders Tracheo-oesophageal fistula	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Ear and labyrinth disorders Vertigo	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Endocrine disorders Adrenal insufficiency	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Eye disorders Cataract	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Abdominal pain	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Anal inflammation	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Diarrhoea	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Faecaloma	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Nausea	4.0% 5/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Oesophageal stenosis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Pancreatitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Stomatitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Vomiting	2.4% 3/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Asthenia	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Fatigue	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Pain	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Pyrexia	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Hepatobiliary disorders Hepatitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Appendicitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Atypical pneumonia	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Bronchitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Epididymitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Escherichia bacteraemia	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Lower respiratory tract infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Lung infection	3.2% 4/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Nosocomial infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Parvovirus infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Pneumocystis jirovecii pneumonia	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Pneumonia	4.0% 5/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Post procedural infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Respiratory tract infection	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Sepsis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Sinusitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Injury, poisoning and procedural complications Fall	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Injury, poisoning and procedural complications Joint dislocation	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Injury, poisoning and procedural complications Radiation oesophagitis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Injury, poisoning and procedural complications Toxicity to various agents	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Injury, poisoning and procedural complications Tracheal haemorrhage	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Alanine aminotransferase increased	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Weight decreased	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Dehydration	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Diabetes mellitus	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Diabetic ketosis	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hyperglycaemia	2.4% 3/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Back pain	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Bone pain	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Muscular weakness	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chordoma	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Altered state of consciousness	1.6% 2/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Cognitive disorder	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Dizziness	2.4% 3/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Encephalopathy	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Headache	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Parkinson's disease	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Partial seizures	0.81% 1/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.

Other adverse events

Other adverse events
Measure	LDK378 Ceritinib) n=124 participants at risk Participants on this arm took oral LDK378 750 mg once daily.
Blood and lymphatic system disorders Anaemia	10.5% 13/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Blood and lymphatic system disorders Neutropenia	8.9% 11/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Abdominal distension	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Abdominal pain	41.1% 51/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Abdominal pain upper	15.3% 19/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Constipation	28.2% 35/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Diarrhoea	85.5% 106/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Dyspepsia	12.1% 15/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Gastrointestinal pain	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Haemorrhoids	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Nausea	78.2% 97/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Stomatitis	11.3% 14/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Gastrointestinal disorders Vomiting	71.8% 89/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Asthenia	15.3% 19/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Chest discomfort	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Fatigue	37.9% 47/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Malaise	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Non-cardiac chest pain	15.3% 19/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
General disorders Pyrexia	18.5% 23/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Influenza	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Nasopharyngitis	14.5% 18/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Pneumonia	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Upper respiratory tract infection	20.2% 25/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Infections and infestations Urinary tract infection	8.1% 10/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Alanine aminotransferase increased	52.4% 65/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Amylase increased	11.3% 14/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Aspartate aminotransferase increased	46.8% 58/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Blood alkaline phosphatase increased	23.4% 29/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Blood creatinine increased	26.6% 33/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Creatinine renal clearance decreased	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Electrocardiogram QT prolonged	16.1% 20/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Gamma-glutamyltransferase increased	29.0% 36/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Lipase increased	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Weight decreased	37.9% 47/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations Weight increased	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Investigations White blood cell count decreased	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Decreased appetite	55.6% 69/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hyperglycaemia	12.1% 15/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hyperkalaemia	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hypokalaemia	11.3% 14/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hyponatraemia	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Metabolism and nutrition disorders Hypophosphataemia	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	20.2% 25/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Back pain	25.8% 32/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Bone pain	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Muscular weakness	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	16.9% 21/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Musculoskeletal and connective tissue disorders Neck pain	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Dizziness	16.9% 21/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Headache	25.0% 31/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Nervous system disorders Paraesthesia	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Psychiatric disorders Insomnia	8.9% 11/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Renal and urinary disorders Dysuria	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Cough	23.4% 29/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 31/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.5% 8/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Productive cough	12.1% 15/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.3% 9/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Skin and subcutaneous tissue disorders Dry skin	9.7% 12/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Skin and subcutaneous tissue disorders Pruritus	14.5% 18/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Skin and subcutaneous tissue disorders Rash	22.6% 28/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 7/124 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 5 years.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER