Trial Outcomes & Findings for LDK378 in Adult Chinese Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib (NCT NCT02040870)

NCT ID: NCT02040870

Last Updated: 2019-02-20

Results Overview

AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time. AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours. AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 103 participants
• Primary outcome timeframe: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))
• Results posted on: 2019-02-20

Participant Flow

Approximately 100 patients were planned to be enrolled, and 103 patients were actually enrolled and analyzed.

Not Completed means that the participants discontinued from the treatment phase

Participant milestones

Measure	LDK378 daily dosing, 28-day cycle patients
Overall Study STARTED	103
Overall Study Entered Post-treatment Follow-up	2
Overall Study Entered Survival Follow-up	75
Overall Study Discontinue From Study	26
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	103

Reasons for withdrawal

Measure	LDK378 daily dosing, 28-day cycle patients
Overall Study Completed treatment phase	6
Overall Study Adverse Event	7
Overall Study Progressive disease	58
Overall Study Physician Decision	6
Overall Study Subject/guardian decision	10
Overall Study Lost to Follow-up	3
Overall Study Death	13

Baseline Characteristics

The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

Baseline characteristics by cohort

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Age, Continuous	49.3 Years STANDARD_DEVIATION 10.89 • n=5 Participants • The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
Sex: Female, Male Female	48 Participants n=5 Participants • The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
Sex: Female, Male Male	55 Participants n=5 Participants • The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
Race/Ethnicity, Customized Chinese	103 Participants n=5 Participants • The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

PRIMARY outcome

Timeframe: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))

Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.

AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time.

AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.

AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf AUClast	10100 ng*hr/mL Geometric Coefficient of Variation 52.6
Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf AUC0-24h	3940 ng*hr/mL Geometric Coefficient of Variation 49.6
Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf AUCinf	11100 ng*hr/mL Geometric Coefficient of Variation 57.7

PRIMARY outcome

Timeframe: Cycle 2 Day 1 (after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.

AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h	22000 ng*hr/mL Geometric Coefficient of Variation 79.7

PRIMARY outcome

Timeframe: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.

Cmax is the maximum (peak) concentration of drug in plasma

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax PK run-in phase	233 ng/mL Geometric Coefficient of Variation 52.2
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax C2D1	1080 ng/mL Geometric Coefficient of Variation 78.0

PRIMARY outcome

Timeframe: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.

Tmax is the time to reach maximum plasma concentration.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax PK run-in phase	5.94 hour Interval 2.95 to 8.08
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax C2D1	5.88 hour Interval 1.75 to 23.4

PRIMARY outcome

Timeframe: up to 41 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

Safety and tolerability of LDK378 at 750 mg once daily dose in Chinese adult patients with ALK-rearranged locally advanced or metastatic NSCLC

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Overall Summary of Adverse Events (AEs) - Per Occurence All deaths	65 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence On-treatment deaths	23 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence Adverse Events (AEs)	103 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs suspected to be drug related	100 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence Serious Adverse Events (SAEs)	36 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence SAEs suspected to be drug related	7 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs leading to discontinuation	15 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs requiring dose interruption	34 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs requiring dose adjustment	49 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs requiring dose adjustment or interruption	64 occurrences
Overall Summary of Adverse Events (AEs) - Per Occurence AEs requiring additional therapy	94 occurrences

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

ORR calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment	41.7 Percentage of participants

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
ORR Per RECIST 1.1 Per Blind Independent Review Committee (BIRC) Assessment	32.0 Percentage of participants Interval 23.2 to 42.0

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=43 Participants daily dosing, 28-day cycle patients
Duration of Response (DOR) Per Investigator Assessment	7.5 months Interval 5.7 to 9.4

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Disease Control Rate (DCR) Per Investigator Assessment	77.7 Percentage of participants Interval 68.4 to 85.3

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=43 Participants daily dosing, 28-day cycle patients
Time to Response (TTR) Per Investigator Assessment	1.90 Months Interval 1.6 to 12.9

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=23 Participants daily dosing, 28-day cycle patients
Overall Intracranial Response Rate (OIRR) Per Investigator Assessment	39.1 Percentage of participants Interval 19.7 to 61.5

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=9 Participants daily dosing, 28-day cycle patients
Overall Intracranial Response Rate (OIRR) Per BIRC Assessment	0 Percentage of participants Interval 0.0 to 33.6

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

PFS, defined as time from first dose of LDK378 to progression or death due to any cause.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Progression Free Survival (PFS) Per Investigator Assessment	7.2 Months Interval 4.1 to 7.5

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

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

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Overall Survival (OS)	17.5 Months Interval 10.8 to 24.3

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=33 Participants daily dosing, 28-day cycle patients
Duration of Response (DOR) Per BIRC Assessment	9.2 months Interval 7.3 to 14.7

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Disease Control Rate (DCR) Per BIRC Assessment	67.0 Percentage of participants Interval 57.0 to 75.9

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Measure	LDK378 n=33 Participants daily dosing, 28-day cycle patients
Time to Response (TTR) Per BIRC Assessment	1.80 Months Interval 1.6 to 3.7

SECONDARY outcome

Timeframe: 40 months

Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.

PFS, defined as time from first dose of LDK378 to progression or death due to any cause.

Outcome measures

Measure	LDK378 n=103 Participants daily dosing, 28-day cycle patients
Progression Free Survival (PFS) Per BIRC Assessment	3.8 Months Interval 3.6 to 5.6

Adverse Events

LDK378

Serious events: 36 serious events

Other events: 101 other events

Deaths: 23 deaths

Serious adverse events

Measure	LDK378 n=103 participants at risk daily dosing, 28-day cycle patients
Cardiac disorders Cardiac failure	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Pericardial effusion	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Supraventricular tachycardia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Ascites	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Gastritis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Intestinal obstruction	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Intussusception	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Vomiting	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Asthenia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Chest discomfort	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Impaired healing	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Lung infection	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Pneumonia	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Pulmonary mycosis	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Injury, poisoning and procedural complications Post procedural oedema	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood bilirubin increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram QT prolonged	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Haemoglobin decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Decreased appetite	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Gout	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Muscular weakness	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer metastatic	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Altered state of consciousness	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Brain oedema	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Coma	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Headache	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Hypoaesthesia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Renal and urinary disorders Renal failure	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Cough	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.

Other adverse events

Measure	LDK378 n=103 participants at risk daily dosing, 28-day cycle patients
Blood and lymphatic system disorders Anaemia	35.0% 36/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Blood and lymphatic system disorders Leukocytosis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Blood and lymphatic system disorders Leukopenia	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Blood and lymphatic system disorders Neutropenia	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Blood and lymphatic system disorders Thrombocytopenia	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Angina pectoris	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Palpitations	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Sinus bradycardia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Supraventricular tachycardia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Cardiac disorders Tachycardia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Ear and labyrinth disorders Deafness	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Ear and labyrinth disorders Ear pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Eye disorders Diplopia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Eye disorders Dry eye	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Eye disorders Vision blurred	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal discomfort	9.7% 10/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal distension	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal pain	21.4% 22/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal pain lower	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Abdominal pain upper	29.1% 30/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Chronic gastritis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Constipation	7.8% 8/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Diarrhoea	74.8% 77/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Dry mouth	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Dysphagia	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Faecaloma	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Flatulence	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Gastritis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Melaena	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Mouth ulceration	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Nausea	58.3% 60/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Oesophageal pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Toothache	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Gastrointestinal disorders Vomiting	61.2% 63/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Asthenia	12.6% 13/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Chest discomfort	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Fatigue	14.6% 15/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Gait disturbance	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Influenza like illness	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Malaise	4.9% 5/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Non-cardiac chest pain	21.4% 22/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Oedema peripheral	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Peripheral swelling	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
General disorders Pyrexia	19.4% 20/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Cholelithiasis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Cholestasis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Gallbladder enlargement	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Hepatic failure	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Hepatic function abnormal	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Hepatobiliary disorders Hepatic pain	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Immune system disorders Contrast media allergy	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Abdominal infection	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Influenza	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Lung infection	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Nasopharyngitis	7.8% 8/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Pneumonia	6.8% 7/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Respiratory tract infection	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Tinea cruris	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Upper respiratory tract infection	11.7% 12/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Infections and infestations Urinary tract infection	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Injury, poisoning and procedural complications Ligament sprain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Injury, poisoning and procedural complications Post procedural oedema	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Alanine aminotransferase increased	59.2% 61/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Amylase increased	5.8% 6/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Apolipoprotein A-I decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Aspartate aminotransferase increased	58.3% 60/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Bilirubin conjugated increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood albumin decreased	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood alkaline phosphatase	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood alkaline phosphatase increased	19.4% 20/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood bilirubin increased	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood calcium decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood calcium increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood cholesterol increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood creatine phosphokinase increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood creatinine increased	33.0% 34/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood glucose decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood glucose increased	8.7% 9/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood phosphorus decreased	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood potassium decreased	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood pressure increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood sodium decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood triglycerides increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood urea increased	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Blood uric acid increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Coagulation time prolonged	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Creatinine renal clearance decreased	22.3% 23/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Creatinine renal clearance increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram QT interval	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram QT prolonged	8.7% 9/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram T wave abnormal	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram T wave inversion	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Electrocardiogram abnormal	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Gamma-glutamyltransferase increased	26.2% 27/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Haemoglobin decreased	8.7% 9/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Heart rate decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Lipase increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Low density lipoprotein increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Lymphocyte count decreased	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Lymphocyte percentage decreased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Neutrophil count decreased	6.8% 7/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Neutrophil count increased	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Neutrophil percentage increased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Platelet count decreased	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Platelet count increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Prothrombin time prolonged	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Red blood cell count decreased	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Transaminases increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Weight decreased	37.9% 39/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations Weight increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations White blood cell count decreased	21.4% 22/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Investigations White blood cell count increased	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Decreased appetite	31.1% 32/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Diabetes mellitus	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hyperglycaemia	8.7% 9/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hyperkalaemia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypoalbuminaemia	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypocalcaemia	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypochloraemia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypokalaemia	10.7% 11/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hyponatraemia	6.8% 7/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypophosphataemia	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Metabolism and nutrition disorders Hypoproteinaemia	4.9% 5/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 5/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Back pain	11.7% 12/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Bone pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Muscle twitching	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Muscular weakness	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	4.9% 5/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.6% 14/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 9/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Musculoskeletal and connective tissue disorders Tenosynovitis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer metastatic	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Brain oedema	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Depressed level of consciousness	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Dizziness	11.7% 12/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Head discomfort	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Headache	11.7% 12/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Hypoaesthesia	2.9% 3/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Migraine	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Nervous system disorders Paraesthesia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Psychiatric disorders Anxiety	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Psychiatric disorders Eating disorder	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Psychiatric disorders Insomnia	6.8% 7/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Renal and urinary disorders Chromaturia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Renal and urinary disorders Dysuria	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Renal and urinary disorders Pollakiuria	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Renal and urinary disorders Renal disorder	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Reproductive system and breast disorders Pelvic pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Asthma	4.9% 5/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Asthma exercise induced	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Choking sensation	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Cough	18.4% 19/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.8% 7/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Hiccups	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Laryngeal stenosis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Productive cough	3.9% 4/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Sneezing	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Respiratory, thoracic and mediastinal disorders Sputum increased	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Alopecia	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Eczema	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Pain of skin	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Pruritus	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Rash	11.7% 12/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Rash pruritic	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Skin and subcutaneous tissue disorders Skin disorder	1.9% 2/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Vascular disorders Hypotension	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Vascular disorders Phlebitis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.
Vascular disorders Vasculitis	0.97% 1/103 • Adverse Events are collected and reported from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 41 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: novartis.email@novartis.com

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