Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)

• ClinicalTrials.gov Identifier: NCT01742286
• Recruitment Status: Completed
• First Posted: December 5, 2012
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: ALK-activated Tumors
• Intervention: Drug: Ceritinib
• Enrollment: 83

Participant Flow

Recruitment Details	Eighty-three patients were treated at different dose levels in both fasted and fed states dose escalation and expansion groups.
Pre-assignment Details	At least 15 patients for the fasted dose escalation & 12 patients for the fed dose escalation were expected to be treated. During the expansion part, approximately 45 patients were planned to be treated on the preferred regimen, approximately 25 patients in group 1 on the preferred regimen, and approximately 20 patients in group 2.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Period Title: Escalation Phase
Started	5	12	6	2	4	5	6
Ended Treatment = Not Completed)	5	12	6	2	4	5	6
Completed	0	0	0	0	0	0	0
Not Completed	5	12	6	2	4	5	6
Reason Not Completed
Administrative problems	1	1	0	0	0	0	2
Adverse Event	0	1	2	0	0	1	0
Disease progression	3	7	4	1	4	3	2
Death	0	0	0	0	0	1	0
Physician Decision	0	3	0	1	0	0	2
Subject/guardian decision	1	0	0	0	0	0	0
Period Title: Expansion Phase
Started	0	0	7	0	0	0	36
End of Treatment = Not Ccompleted	0	0	7	0	0	0	36
Completed	0	0	0	0	0	0	0
Not Completed	0	0	7	0	0	0	36
Reason Not Completed
Administrative problems	0	0	0	0	0	0	5
Physician Decision	0	0	4	0	0	0	9
Adverse Event	0	0	0	0	0	0	6
Disease progression	0	0	3	0	0	0	15
Withdrawal by Subject	0	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title		Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2	Total
Arm/Group Description		Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib	Total of all reporting groups
Overall Number of Baseline Participants		5	12	13	2	4	5	42	83
Baseline Analysis Population Description		The Full analysis set (FAS) included all patients who received at least one dose of ceritinib.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	5 participants	12 participants	13 participants	2 participants	4 participants	5 participants	42 participants	83 participants
		11.6 (5.27)	10.0 (4.94)	9.2 (5.34)	9.0 (9.90)	8.8 (4.99)	9.2 (4.02)	7.3 (4.73)	8.5 (4.97)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	5 participants	12 participants	13 participants	2 participants	4 participants	5 participants	42 participants	83 participants
1 - < 7 yrs		1	4	6	1	2	2	21	37
7 - < 12 yrs		2	2	1	0	0	1	10	16
12 - < 18 yrs		2	6	6	1	2	2	11	30
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	12 participants	13 participants	2 participants	4 participants	5 participants	42 participants	83 participants
	Female	3 60.0%	3 25.0%	5 38.5%	1 50.0%	1 25.0%	3 60.0%	14 33.3%	30 36.1%
	Male	2 40.0%	9 75.0%	8 61.5%	1 50.0%	3 75.0%	2 40.0%	28 66.7%	53 63.9%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	5 participants	12 participants	13 participants	2 participants	4 participants	5 participants	42 participants	83 participants
Asian		0	1	1	0	0	0	3	5
Black		0	1	0	0	0	0	0	1
Caucasian		5	7	11	2	4	3	33	65
Other		0	3	1	0	0	2	5	11
Native American		0	0	0	0	0	0	1	1

Outcome Measures

1. Primary Outcome

Title	Incidence Rate of Dose Limiting Toxicities (DLTs) Occurring During First Cycle of Treatment
Description	A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 21 days of treatment with LDK378 and meets a specified defined criteria. A participant with multiple occurrences of DLTs under one treatment is counted only once in the Adverse Event category for that treatment. A participant with multiple DLTs within a primary system organ class is counted only once in the total row.
Time Frame	up to day 21 after the patient's first dose; cycle = within the first 21 days of patient's first dose

Outcome Measure Data

Analysis Population Description

The dose determining analysis set (DDS) consisted of all patients from the Safety set who either met the minimum exposure criterion and had sufficient safety evaluations or discontinued earlier due to DLT in the escalation phase.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	4	12	6	2	4	4	5
Measure Type: Number; Unit of Measure: Participants
Investigations: Alanine aminotransferase incr.	0	0	0	1	0	1	0
Gastrointestinal disorders: abdominal pain	0	0	0	1	0	0	0
Gastrointestinal disorders: Influenza	0	0	0	0	0	0	1
Total DLTs	0	0	0	2	0	1	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fasted: Ceritinib 300 mg/m2, Fasted: Ceritinib 450 mg/m2, Fasted: Ceritinib 510 mg/m2, Fasted: Ceritinib 560 mg/m2
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	MTD/RDE
	Estimated Value	510
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fed: Ceritinib 320 mg/m2, Fed: Ceritinib 400 mg/m2, Fed: Ceritinib 500 mg/m2
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	MTD/RDE
	Estimated Value	500
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Summary of Best Overall Response by Overall Response Rate (ORR) Per Investigator Assessment
Description	ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). ORR was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma & other solid tumors): 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 lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)/Maximum Tolerated Dose MTD)/Recommended dose for expansion (RDE): Results are presented only for patients who received at least 1 dose of ceritinib in either of the 2 MTD/RDE groups and were based on combining data from across the dose-escalation & dose-expansion phases, & summarized according to primary diagnosis of tumor.

Arm/Group Title	ALK-activated Neuroblastoma	ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	ALK-activated Other
Arm/Group Description:	Participants with ALK-activated neuroblastoma enrolled in the expansion part of the study and were given ceritinib once daily, continuously	Participants with ALK-activated IMT enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with ALK-activated ALCL enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with other ALK-activated tumors enrolled in the expansion part of the study who were given ceritinib once daily, continuously
Overall Number of Participants Analyzed	30	10	8	7
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.0; (7.7 to 38.6)	70.0; (34.8 to 93.3)	75.0; (34.9 to 96.8)	14.3; (0.4 to 57.9)

3. Secondary Outcome

Title	Duration of Response (DoR) Per Investigator Assessment
Description	DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression (PD) or death due to any cause. DOR was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma & other solid tumors): 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 lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set/MTD/RDE patients with confirmed CR or PR): Efficacy results are presented only for patients with confirmed CR or PR who received at least 1 dose of ceritinib in either of the 2 MTD/RDE groups & were based on combining data from across the dose-escalation & dose-expansion phases, & summarized according to primary tumor diagnosis.

Arm/Group Title	ALK-activated Neuroblastoma	ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	ALK-activated Other
Arm/Group Description:	Participants with ALK-activated neuroblastoma enrolled in the expansion part of the study and were given ceritinib once daily, continuously	Participants with ALK-activated IMT enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with ALK-activated ALCL enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with other ALK-activated tumors enrolled in the expansion part of the study who were given ceritinib once daily, continuously
Overall Number of Participants Analyzed	6	7	6	1
Median (95% Confidence Interval); Unit of Measure: months
	15.0; (5.8 to 22.2)	NA [1]; (3.5 to NA)	NA [1]; (2.8 to NA)	NA [1]; (NA to NA)

[1]

N/A: Median not reached for subjects with ALCL, IMT & Other tumor types as most of the subjects did not have a DOR event (progression or death).

4. Secondary Outcome

Title	Progression Free Survival (PFS) Based on Investigator Assessment
Description	PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma & other solid tumors): 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 lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Time Frame	30 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)/MTD/RDE: Efficacy results are presented only for patients who received at least 1 dose of ceritinib in either of the two MTD/RDE groups and were based on combining data from across the dose-escalation & dose-expansion phases, & summarized according to primary diagnosis of tumor.

Arm/Group Title	ALK-activated Neuroblastoma	ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	ALK-activated Other
Arm/Group Description:	Participants with ALK-activated neuroblastoma enrolled in the expansion part of the study and were given ceritinib once daily, continuously	Participants with ALK-activated IMT enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with ALK-activated ALCL enrolled in the expansion part of the study who were given ceritinib once daily, continuously	Participants with other ALK-activated tumors enrolled in the expansion part of the study who were given ceritinib once daily, continuously
Overall Number of Participants Analyzed	30	10	8	7
Median (95% Confidence Interval); Unit of Measure: months
	2.4; (1.2 to 6.8)	NA [1]; (1.2 to NA)	NA [1]; (4.1 to NA)	1.9 [1]; (1.2 to NA)

[1]

N/A: The median was not reached for subjects with IMT and ALCL

5. Secondary Outcome

Title	Plasma Concentration Time Profiles by Treatment Group in Escalation Phase
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Only PK plasma concentrations with non-missing sampling date and time, and for which the last dose date and time prior to the PK sample draw are non-missing, were included in the PK analysis.
Time Frame	0hr pre-dose, 2hrs post-dose, 4hrs post-dose, 6hrs post-dose & 24hrs post-dose in Cycle1 Day1 & Cycle 2 day 1; 0hr pre-dose in Cycle 1 Day 15, Cycle 2 Day1, Cycle 2 Day 2, Cycle 3 day 1 & Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title		Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:		Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed		5	12	6	2	4	5	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Cycle1 Day1 (C1D1) 0 hr pre-dose	Number Analyzed	5 participants	12 participants	6 participants	2 participants	4 participants	5 participants	5 participants
		0.0; (0.0%)	0.0; (0.0%)	0.0; (0.0%)	0.0; (0.0%)	0.0; (0.0%)	0.0; (0.0%)	0.0; (0.0%)
C1D1 2 hrs post-dose	Number Analyzed	5 participants	11 participants	6 participants	2 participants	4 participants	5 participants	5 participants
		104; (97.9%)	99.0; (94.7%)	112; (90.6%)	126; (0.6%)	52.4; (138.1%)	197; (58.3%)	72.5; (82.3%)
C1D1 4 hrs post-dose	Number Analyzed	5 participants	11 participants	6 participants	2 participants	4 participants	5 participants	5 participants
		216; (39.6%)	233; (69.0%)	250; (93.5%)	350; (54.7%)	166; (92.8%)	311; (28.1%)	153; (34.1%)
C1D1 6 hrs post-dose	Number Analyzed	5 participants	11 participants	6 participants	2 participants	4 participants	5 participants	4 participants
		227; (33.8%)	245; (78.1%)	245; (97.2%)	423; (74.2%)	275; (35.3%)	318; (36.7%)	168; (68.9%)
C1D1 24 hrs post-dose	Number Analyzed	5 participants	11 participants	6 participants	2 participants	4 participants	5 participants	4 participants
		130; (66.3%)	141; (89.9%)	86.4; (117.2%)	268; (73.6%)	98.5; (63.7%)	126; (107.7%)	161; (111.3%)
C1D2 0 hr pre-dose	Number Analyzed	5 participants	11 participants	6 participants	2 participants	4 participants	5 participants	4 participants
		130; (66.3%)	141; (89.9%)	86.4; (117.2%)	268; (73.6%)	98.5; (63.7%)	126; (107.7%)	161; (111.3%)
C1D15 0 hr pre-dose	Number Analyzed	5 participants	12 participants	6 participants	2 participants	3 participants	4 participants	5 participants
		193; (99.6%)	618; (64.6%)	537; (49.9%)	942; (5.1%)	262; (118.4%)	379; (119.2%)	461; (76.3%)
C2D1 0 hr pre-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	3 participants
		169; (299.5%)	661; (53.5%)	672; (45.4%)	695; (152.7%)	218; (103.7%)	429; (73.8%)	655; (12.4%)
C2D1 2 hrs post-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	3 participants
		287; (85.4%)	687; (61.6%)	801; (45.9%)	662; (99.6%)	196; (112.4%)	475; (96.6%)	718; (21.1%)
C2D1 4 hrs post-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	3 participants
		386; (47.6%)	810; (51.9%)	1000; (30.4%)	1230; (30.1%)	262; (133.9%)	631; (86.6%)	744; (13.2%)
C2D1 6 hrs post-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	2 participants
		426; (38.4%)	852; (47.8%)	898; (37.6%)	1260; (16.4%)	300; (130.3%)	648; (105.5%)	786; (7.7%)
C2D1 24 hrs post-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	5 participants
		247; (46.9%)	651; (53.7%)	714; (40.8%)	847; (72.2%)	194; (106.5%)	411; (147.3%)	448; (43.9%)
C2D2 0 hr pre-dose	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	5 participants
		247; (46.9%)	651; (53.7%)	714; (40.8%)	847; (72.2%)	194; (106.5%)	411; (147.3%)	448; (43.9%)
C3D1 0 hr pre-dose	Number Analyzed	2 participants	8 participants	4 participants	1 participants	2 participants	1 participants	5 participants
		399; (94.4%)	810; (34.3%)	415; (117.7%)	1320; (0.0%)	167; (218.3%)	328; (0.0%)	433; (128.5%)
C4D1 0 hr pre-dose	Number Analyzed	2 participants	8 participants	4 participants	1 participants	1 participants	1 participants	3 participants
		503; (35.1%)	960; (36.2%)	321; (874.8%)	857; (0.0%)	403; (0.0%)	1320; (0.0%)	658; (27.0%)

6. Secondary Outcome

Title	Plasma Concentration Time Profiles by Treatment Group in Expansion Phase
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Only PK plasma concentrations with non-missing sampling date and time, and for which the last dose date and time prior to the PK sample draw are non-missing, were included in the PK analysis.
Time Frame	0hr pre-dose Cycle 1 Day 1, cycle 1 Day 15; 0hr pre-dose, 2hrs post-dose, 4hrs post-dose, 6hrs post-dose & 24hrs post-dose in Cycle2 Day1; 0hr pre-dose in Cycle2 Day2, Cycle 3 Day 1 & Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title		Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:		Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed		0	0	7	0	0	0	16
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
C1D1 0 hr pre-dose	Number Analyzed	0 participants	0 participants	6 participants	0 participants	0 participants	0 participants	9 participants
				0.0; (0.0%)				0.0; (0.0%)
C1D15 0 hr post-dose	Number Analyzed	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
				1190; (0.0%)
C2D1 0 hr pre-dose	Number Analyzed	0 participants	0 participants	7 participants	0 participants	0 participants	0 participants	16 participants
				529; (365.4%)				627; (93.6%)
C2D1 2 hrs post-dose	Number Analyzed	0 participants	0 participants	7 participants	0 participants	0 participants	0 participants	15 participants
				798; (69.0%)				729; (72.3%)
C2D1 4 hrs post-dose	Number Analyzed	0 participants	0 participants	7 participants	0 participants	0 participants	0 participants	14 participants
				863; (65.2%)				828; (47.9%)
C2D1 6 hrs post-dose	Number Analyzed	0 participants	0 participants	7 participants	0 participants	0 participants	0 participants	15 participants
				939; (71.4%)				870; (52.6%)
C2D1 24 hrs post-dose	Number Analyzed	0 participants	0 participants	6 participants	0 participants	0 participants	0 participants	14 participants
				615; (119.9%)				596; (75.5%)
C2D2 0 hr pre-dose	Number Analyzed	0 participants	0 participants	6 participants	0 participants	0 participants	0 participants	14 participants
				615; (119.9%)				596; (75.5%)
C3D1 0 hr pre-dose	Number Analyzed	0 participants	0 participants	5 participants	0 participants	0 participants	0 participants	14 participants
				836; (60.4%)				573; (134.2%)
C4D1 0 hr pre-dose	Number Analyzed	0 participants	0 participants	5 participants	0 participants	0 participants	0 participants	12 participants
				834; (78.8%)				622; (96.5%)

7. Secondary Outcome

Title	Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the concentration-time curve from time zero to the last measureable concentration time AUC0-24h: Area under the plasma concentration-time curve t=0-24 h
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title		Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:		Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed		5	10	3	1	3	4	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr*ng/mL
AUC0-24h	Number Analyzed	4 participants	3 participants	2 participants	0 participants	1 participants	1 participants	2 participants
		3920; (39.9%)	5220; (58.0%)	8750; (11.1%)		5720; (0.0%)	7272; (0.0%)	4730; (59.4%)
AUClast	Number Analyzed	5 participants	9 participants	3 participants	1 participants	3 participants	4 participants	3 participants
		4260; (39.3%)	4350; (91.8%)	7670; (24.5%)	4860; (0.0%)	3730; (48.6%)	5760; (49.1%)	4940; (32.6%)

8. Secondary Outcome

Title	Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the concentration-time curve from time zero to the last measureable concentration time; AUC0-24h: Area under the plasma concentration-time curve t=0-24 h
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title		Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:		Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed		5	12	5	2	3	4	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr*ng/mL
AUC0-24h	Number Analyzed	5 participants	7 participants	2 participants	2 participants	1 participants	1 participants	1 participants
		8160; (44.0%)	16900; (59.1%)	21000; (20.8%)	25300; (39.2%)	2100; (0.0%)	30500; (0.0%)	16500; (0.0%)
AUClast	Number Analyzed	5 participants	12 participants	5 participants	2 participants	3 participants	4 participants	2 participants
		8210; (44.3%)	18000; (50.0%)	17200; (51.2%)	25600; (39.0%)	5840; (118.4%)	125000; (113.2%)	16700; (1.8%)

9. Secondary Outcome

Title	Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. In this phase ceritinib was expanded at 500mg/m2 fed and 510mg/m2 fasted administered orally once daily and was assessed only at steady state, Cycle 2 Day 1. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the plasma (serum, or blood) concentration versus time curverea under the concentration-time curve from time zero to the last measureable concentration time AUC0-24h: Area under the plasma concentration-time curve t=0-24 h
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS), MTD/RDE consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title		Fasted: Ceritinib 510 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:		Participants in the fasted group who took 510 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed		4	14
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr*ng/mL
AUC0-24h	Number Analyzed	0 participants	6 participants
			15900; (93.8%)
AUClast	Number Analyzed	4 participants	14 participants
		24100; (38.9%)	16100; (61.2%)

10. Secondary Outcome

Title	PK Parameter: Cmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	5	10	3	1	3	4	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	258; (39.0%)	270; (82.1%)	537; (22.2%)	265; (0.0%)	251; (37.0%)	341; (34.2%)	204; (54.6%)

11. Secondary Outcome

Title	PK Parameter: Cmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug.
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	5	12	5	2	3	4	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	427; (38.5%)	870; (48.7%)	1020; (32.1%)	1300; (21.4%)	300; (130.3%)	674; (93.8%)	804; (10.4%)

12. Secondary Outcome

Title	PK Parameter: Cmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. In this phase ceritinib was expanded at 500mg/m2 fed and 510mg/m2 fasted administered orally once daily and was assessed only at steady state, Cycle 2 Day 1. Cmax: Maximum (peak) concentration of drug
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS), MTD/RDE consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 510 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	4	14
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	1220; (40.2%)	890; (50.9%)

13. Secondary Outcome

Title	PK Parameter: Tmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	5	10	3	1	3	4	3
Median (Full Range); Unit of Measure: hour (hr)
	4.20; (1.90 to 24.0)	4.25; (0.00 to 6.10)	4.30; (4.10 to 6.00)	6.10; (6.10 to 6.10)	6.10; (5.70 to 6.30)	6.00; (4.30 to 6.20)	5.80; (4.10 to 6.10)

14. Secondary Outcome

Title	PK Parameter: Tmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	5	12	5	2	3	4	2
Median (Full Range); Unit of Measure: hour (hr)
	6.00; (4.10 to 6.70)	5.10; (2.00 to 6.60)	4.00; (2.10 to 6.00)	3.95; (0.00 to 6.70)	5.90; (5.80 to 6.10)	6.00; (4.00 to 6.10)	2.20; (2.00 to 2.40)

15. Secondary Outcome

Title	PK Parameter: Tmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. In this phase ceritinib was expanded at 500mg/m2 fed and 510mg/m2 fasted administered orally once daily and was assessed only at steady state, Cycle 2 Day 1. Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS), MTD/RDE consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 510 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	4	14
Median (Full Range); Unit of Measure: hour (hr)
	6.20; (3.80 to 23.8)	5.90; (1.90 to 23.6)

16. Secondary Outcome

Title	PK Parameter: Racc in Dose Escalation Phase Cycle 2 Day 1
Description	Characterize single and multiple-dose PK of LDK378 in pediatric patients. Racc: Accumulation ratio
Time Frame	0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set (PAS) consisted of all patients who received at least one dose of ceritinib and had at least one evaluable PK sample.

Arm/Group Title	Fasted: Ceritinib 300 mg/m2	Fasted: Ceritinib 450 mg/m2	Fasted: Ceritinib 510 mg/m2	Fasted: Ceritinib 560 mg/m2	Fed: Ceritinib 320 mg/m2	Fed: Ceritinib 400 mg/m2	Fed: Ceritinib 500 mg/m2
Arm/Group Description:	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib
Overall Number of Participants Analyzed	5	12	5	2	3	4	2
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
	1.93; (64.2%)	5.50; (30.3%)	2.56; (0.0%)	6.86; (0.0%)	0.533; (0.0%)	3.41; (0.0%)	3.62; (0.0%)

Adverse Events

Time Frame	Adverse events (AEs) were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 63.7 months.
Adverse Event Reporting Description	AE is any sign or symptom that occurs during the study treatment plus the 30 days post treatment
Arm/Group Title	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
Arm/Group Description	Participants in the fasted group who took 300 mg of ceritinib	Participants in the fasted group who took 450 mg of ceritinib	Participants in the fasted group who took 510 mg of ceritinib	Participants in the fasted group who took 560 mg of ceritinib	Participants in the fed group who took 320 mg of ceritinib	Participants in the fed group who took 400 mg of ceritinib	Participants in the fed group who took 500 mg of ceritinib	All participants in the Fasted and Fed groups
All-Cause Mortality
	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/5 (20.00%)	1/12 (8.33%)	2/13 (15.38%)	0/2 (0.00%)	2/4 (50.00%)	1/5 (20.00%)	5/42 (11.90%)	12/83 (14.46%)
Serious Adverse Events
	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/5 (20.00%)	4/12 (33.33%)	8/13 (61.54%)	2/2 (100.00%)	3/4 (75.00%)	1/5 (20.00%)	21/42 (50.00%)	40/83 (48.19%)
Blood and lymphatic system disorders
Anaemia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Febrile bone marrow aplasia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Febrile neutropenia † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Thrombocytopenia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Cardiac disorders
Cardiac failure † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Pericarditis † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Gastrointestinal disorders
Abdominal distension † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Abdominal pain † 1	1/5 (20.00%)	0/12 (0.00%)	1/13 (7.69%)	1/2 (50.00%)	1/4 (25.00%)	0/5 (0.00%)	1/42 (2.38%)	5/83 (6.02%)
Ascites † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Dental caries † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Gastric haemorrhage † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Small intestinal haemorrhage † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Subileus † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Vomiting † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
General disorders
Chest pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	0/42 (0.00%)	2/83 (2.41%)
General physical health deterioration † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Multiple organ dysfunction syndrome † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pyrexia † 1	1/5 (20.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	6/83 (7.23%)
Hepatobiliary disorders
Acute hepatic failure † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hepatotoxicity † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Infections and infestations
Appendicitis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Device related infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	4/42 (9.52%)	4/83 (4.82%)
Ear infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Encephalitis † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Enterovirus infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Gastroenteritis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	2/83 (2.41%)
Infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Influenza † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Metapneumovirus infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Pneumonia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pneumonia viral † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Pyelonephritis † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Sepsis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Septic shock † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Staphylococcal infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Tonsillitis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Wound infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Investigations
Alanine aminotransferase increased † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Amylase increased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Aspartate aminotransferase increased † 1	0/5 (0.00%)	1/12 (8.33%)	2/13 (15.38%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	4/83 (4.82%)
Blood lactate dehydrogenase increased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
C-reactive protein increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Lipase increased † 1	0/5 (0.00%)	0/12 (0.00%)	2/13 (15.38%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Metabolism and nutrition disorders
Dehydration † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Hypoglycaemia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Musculoskeletal and connective tissue disorders
Bone pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Nervous system disorders
Hemiplegia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Seizure † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	2/83 (2.41%)
Psychiatric disorders
Suicide attempt † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	2/83 (2.41%)
Renal and urinary disorders
Acute kidney injury † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Respiratory, thoracic and mediastinal disorders
Bronchopleural fistula † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pneumothorax † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Respiratory failure † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	1/83 (1.20%)
Vascular disorders
Hypotension † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
1 Term from vocabulary, MedDRA (21.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/5 (100.00%)	12/12 (100.00%)	13/13 (100.00%)	2/2 (100.00%)	4/4 (100.00%)	5/5 (100.00%)	42/42 (100.00%)	83/83 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	1/5 (20.00%)	3/12 (25.00%)	3/13 (23.08%)	1/2 (50.00%)	3/4 (75.00%)	0/5 (0.00%)	11/42 (26.19%)	22/83 (26.51%)
Bone marrow disorder † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Leukocytosis † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Leukopenia † 1	1/5 (20.00%)	0/12 (0.00%)	2/13 (15.38%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	5/42 (11.90%)	8/83 (9.64%)
Lymphadenopathy † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Neutropenia † 1	1/5 (20.00%)	1/12 (8.33%)	3/13 (23.08%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	5/42 (11.90%)	10/83 (12.05%)
Thrombocytopenia † 1	0/5 (0.00%)	2/12 (16.67%)	2/13 (15.38%)	2/2 (100.00%)	2/4 (50.00%)	0/5 (0.00%)	11/42 (26.19%)	19/83 (22.89%)
Cardiac disorders
Left ventricular dysfunction † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Palpitations † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Pericardial effusion † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Tachycardia † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Ear and labyrinth disorders
Ear pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	4/83 (4.82%)
External ear inflammation † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hypoacusis † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Endocrine disorders
Delayed puberty † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hypothyroidism † 1	0/5 (0.00%)	0/12 (0.00%)	2/13 (15.38%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Eye disorders
Eye pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Eye swelling † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Ocular discomfort † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Vision blurred † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Gastrointestinal disorders
Abdominal discomfort † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Abdominal pain † 1	3/5 (60.00%)	6/12 (50.00%)	6/13 (46.15%)	2/2 (100.00%)	2/4 (50.00%)	1/5 (20.00%)	22/42 (52.38%)	42/83 (50.60%)
Abdominal pain upper † 1	0/5 (0.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	1/5 (20.00%)	3/42 (7.14%)	7/83 (8.43%)
Anal fissure † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Anal incontinence † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Anal inflammation † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Constipation † 1	3/5 (60.00%)	2/12 (16.67%)	2/13 (15.38%)	1/2 (50.00%)	1/4 (25.00%)	1/5 (20.00%)	4/42 (9.52%)	14/83 (16.87%)
Diarrhoea † 1	4/5 (80.00%)	12/12 (100.00%)	10/13 (76.92%)	2/2 (100.00%)	2/4 (50.00%)	3/5 (60.00%)	32/42 (76.19%)	65/83 (78.31%)
Dyspepsia † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	4/42 (9.52%)	6/83 (7.23%)
Flatulence † 1	1/5 (20.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	1/42 (2.38%)	4/83 (4.82%)
Gastrointestinal disorder † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Gingival pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Haematemesis † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Haematochezia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Nausea † 1	2/5 (40.00%)	8/12 (66.67%)	10/13 (76.92%)	1/2 (50.00%)	2/4 (50.00%)	3/5 (60.00%)	21/42 (50.00%)	47/83 (56.63%)
Odynophagia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Proctalgia † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Rectal haemorrhage † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Stomatitis † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	6/83 (7.23%)
Vomiting † 1	4/5 (80.00%)	10/12 (83.33%)	13/13 (100.00%)	2/2 (100.00%)	4/4 (100.00%)	3/5 (60.00%)	36/42 (85.71%)	72/83 (86.75%)
General disorders
Asthenia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	9/42 (21.43%)	10/83 (12.05%)
Catheter site pain † 1	0/5 (0.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	3/83 (3.61%)
Chest pain † 1	0/5 (0.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	1/5 (20.00%)	6/42 (14.29%)	11/83 (13.25%)
Fatigue † 1	3/5 (60.00%)	4/12 (33.33%)	3/13 (23.08%)	2/2 (100.00%)	1/4 (25.00%)	0/5 (0.00%)	9/42 (21.43%)	22/83 (26.51%)
Gait disturbance † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
General physical health deterioration † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Influenza like illness † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Malaise † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Oedema peripheral † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	2/4 (50.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Pyrexia † 1	3/5 (60.00%)	4/12 (33.33%)	6/13 (46.15%)	1/2 (50.00%)	0/4 (0.00%)	1/5 (20.00%)	20/42 (47.62%)	35/83 (42.17%)
Secretion discharge † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Ulcer † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hepatobiliary disorders
Hepatomegaly † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hyperbilirubinaemia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Infections and infestations
Bacterial vulvovaginitis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Bronchitis † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Conjunctivitis † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	5/83 (6.02%)
Device related infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Ear infection † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Gastroenteritis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	4/42 (9.52%)	4/83 (4.82%)
Genital candidiasis † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Human herpesvirus 6 infection † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Influenza † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Molluscum contagiosum † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Mycoplasma infection † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Nasopharyngitis † 1	2/5 (40.00%)	1/12 (8.33%)	2/13 (15.38%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	4/42 (9.52%)	10/83 (12.05%)
Oral herpes † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pharyngitis † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Pneumonia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Rhinitis † 1	0/5 (0.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	8/42 (19.05%)	11/83 (13.25%)
Sinusitis † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Upper respiratory tract infection † 1	1/5 (20.00%)	2/12 (16.67%)	3/13 (23.08%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	8/42 (19.05%)	15/83 (18.07%)
Urinary tract infection † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	0/42 (0.00%)	3/83 (3.61%)
Varicella † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Viral infection † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Wound infection † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Injury, poisoning and procedural complications
Contusion † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Fall † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Hand fracture † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Muscle injury † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Investigations
Alanine aminotransferase increased † 1	1/5 (20.00%)	8/12 (66.67%)	8/13 (61.54%)	2/2 (100.00%)	3/4 (75.00%)	2/5 (40.00%)	30/42 (71.43%)	54/83 (65.06%)
Amylase increased † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	3/42 (7.14%)	6/83 (7.23%)
Aspartate aminotransferase increased † 1	1/5 (20.00%)	6/12 (50.00%)	7/13 (53.85%)	2/2 (100.00%)	3/4 (75.00%)	1/5 (20.00%)	28/42 (66.67%)	48/83 (57.83%)
Blood albumin decreased † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Blood alkaline phosphatase increased † 1	1/5 (20.00%)	4/12 (33.33%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	4/42 (9.52%)	10/83 (12.05%)
Blood bicarbonate decreased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Blood bilirubin increased † 1	0/5 (0.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	5/42 (11.90%)	8/83 (9.64%)
Blood creatine increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Blood creatine phosphokinase MB increased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Blood creatine phosphokinase increased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Blood creatinine increased † 1	2/5 (40.00%)	4/12 (33.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	11/42 (26.19%)	18/83 (21.69%)
Blood glucose increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	0/42 (0.00%)	1/83 (1.20%)
Blood lactate dehydrogenase increased † 1	0/5 (0.00%)	2/12 (16.67%)	3/13 (23.08%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	5/42 (11.90%)	11/83 (13.25%)
Blood magnesium increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Blood pressure increased † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Blood urea increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Blood uric acid increased † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	4/83 (4.82%)
C-reactive protein increased † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	1/5 (20.00%)	4/42 (9.52%)	6/83 (7.23%)
Electrocardiogram QT prolonged † 1	0/5 (0.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Gamma-glutamyltransferase increased † 1	0/5 (0.00%)	3/12 (25.00%)	3/13 (23.08%)	1/2 (50.00%)	2/4 (50.00%)	3/5 (60.00%)	14/42 (33.33%)	26/83 (31.33%)
Haemoglobin decreased † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Lipase increased † 1	0/5 (0.00%)	0/12 (0.00%)	2/13 (15.38%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	6/42 (14.29%)	9/83 (10.84%)
Lymphocyte count decreased † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Neutrophil count decreased † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	2/42 (4.76%)	5/83 (6.02%)
Platelet count decreased † 1	1/5 (20.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Prothrombin time prolonged † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Prothrombin time shortened † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Troponin increased † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Tumour marker increased † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Weight decreased † 1	1/5 (20.00%)	2/12 (16.67%)	3/13 (23.08%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	6/42 (14.29%)	13/83 (15.66%)
White blood cell count decreased † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	4/83 (4.82%)
White blood cell count increased † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Metabolism and nutrition disorders
Decreased appetite † 1	3/5 (60.00%)	4/12 (33.33%)	0/13 (0.00%)	2/2 (100.00%)	1/4 (25.00%)	0/5 (0.00%)	16/42 (38.10%)	26/83 (31.33%)
Dehydration † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Electrolyte imbalance † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Fluid retention † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hyperkalaemia † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Hypermagnesaemia † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Hypoalbuminaemia † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	4/42 (9.52%)	5/83 (6.02%)
Hypocalcaemia † 1	1/5 (20.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	4/83 (4.82%)
Hypokalaemia † 1	3/5 (60.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	7/42 (16.67%)	12/83 (14.46%)
Hypomagnesaemia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	5/83 (6.02%)
Hyponatraemia † 1	2/5 (40.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	7/83 (8.43%)
Hypophosphataemia † 1	2/5 (40.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	2/42 (4.76%)	8/83 (9.64%)
Obesity † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	1/42 (2.38%)	4/83 (4.82%)
Back pain † 1	1/5 (20.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	4/42 (9.52%)	6/83 (7.23%)
Bone pain † 1	1/5 (20.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	2/42 (4.76%)	6/83 (7.23%)
Groin pain † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Joint range of motion decreased † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Muscle spasms † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Muscular weakness † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Musculoskeletal chest pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Musculoskeletal pain † 1	0/5 (0.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	5/83 (6.02%)
Neck pain † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Pain in extremity † 1	1/5 (20.00%)	5/12 (41.67%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	1/5 (20.00%)	5/42 (11.90%)	13/83 (15.66%)
Torticollis † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Tumour pain † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Nervous system disorders
Dizziness † 1	0/5 (0.00%)	2/12 (16.67%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	5/83 (6.02%)
Dysaesthesia † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Dysgeusia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Headache † 1	3/5 (60.00%)	4/12 (33.33%)	1/13 (7.69%)	0/2 (0.00%)	2/4 (50.00%)	1/5 (20.00%)	8/42 (19.05%)	19/83 (22.89%)
Hypertonia † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Lethargy † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Migraine † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Neuralgia † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Somnolence † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Syncope † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Tremor † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Psychiatric disorders
Anxiety † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Irritability † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Mental disorder † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Restlessness † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Sleep disorder † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Renal and urinary disorders
Dysuria † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Micturition urgency † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pollakiuria † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Reproductive system and breast disorders
Dysmenorrhoea † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Cough † 1	1/5 (20.00%)	1/12 (8.33%)	2/13 (15.38%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	8/42 (19.05%)	13/83 (15.66%)
Dyspnoea † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	1/5 (20.00%)	4/42 (9.52%)	6/83 (7.23%)
Dyspnoea exertional † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Emphysema † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Epistaxis † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Nasal congestion † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Oropharyngeal pain † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	5/83 (6.02%)
Pleural effusion † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	3/83 (3.61%)
Pleuritic pain † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Rhinorrhoea † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	4/83 (4.82%)
Upper-airway cough syndrome † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Skin and subcutaneous tissue disorders
Acne † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	2/42 (4.76%)	4/83 (4.82%)
Alopecia † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	3/83 (3.61%)
Eczema † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Erythema † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	4/42 (9.52%)	4/83 (4.82%)
Night sweats † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
Pain of skin † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pruritus † 1	0/5 (0.00%)	2/12 (16.67%)	2/13 (15.38%)	1/2 (50.00%)	0/4 (0.00%)	1/5 (20.00%)	1/42 (2.38%)	7/83 (8.43%)
Rash † 1	0/5 (0.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	6/42 (14.29%)	8/83 (9.64%)
Rash erythematous † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Rash maculo-papular † 1	0/5 (0.00%)	3/12 (25.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	5/83 (6.02%)
Skin exfoliation † 1	0/5 (0.00%)	2/12 (16.67%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Skin hyperpigmentation † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Skin irritation † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Skin lesion † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Swelling face † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Urticaria † 1	0/5 (0.00%)	1/12 (8.33%)	0/13 (0.00%)	0/2 (0.00%)	1/4 (25.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Vascular disorders
Embolism † 1	1/5 (20.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Haematoma † 1	0/5 (0.00%)	1/12 (8.33%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	2/83 (2.41%)
Hypertension † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	1/2 (50.00%)	0/4 (0.00%)	0/5 (0.00%)	1/42 (2.38%)	2/83 (2.41%)
Hypotension † 1	0/5 (0.00%)	0/12 (0.00%)	1/13 (7.69%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	0/42 (0.00%)	1/83 (1.20%)
Pallor † 1	0/5 (0.00%)	0/12 (0.00%)	0/13 (0.00%)	0/2 (0.00%)	0/4 (0.00%)	0/5 (0.00%)	3/42 (7.14%)	3/83 (3.61%)
1 Term from vocabulary, MedDRA (21.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Study Director
• Phone: 862-778-8300
• EMail: novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fischer M, Moreno L, Ziegler DS, Marshall LV, Zwaan CM, Irwin MS, Casanova M, Sabado C, Wulff B, Stegert M, Wang L, Hurtado FK, Branle F, Geoerger B, Schulte JH. Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol. 2021 Dec;22(12):1764-1776. doi: 10.1016/S1470-2045(21)00536-2. Epub 2021 Nov 12.

Brivio E, Zwaan CM. ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects. Pediatr Blood Cancer. 2019 May;66(5):e27645. doi: 10.1002/pbc.27645. Epub 2019 Jan 29.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01742286
• Other Study ID Numbers: CLDK378X2103; 2012-002074-31 ( EudraCT Number )
• First Submitted: November 30, 2012
• First Posted: December 5, 2012
• Results First Submitted: October 24, 2019
• Results First Posted: June 9, 2020
• Last Update Posted: June 9, 2020