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A Phase II, Open Label, Multiple Arm Study of AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02276027
Recruitment Status : Completed
First Posted : October 27, 2014
Results First Posted : December 16, 2020
Last Update Posted : December 16, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma
Interventions Drug: BYL719
Drug: INC280
Drug: LDK378
Drug: MEK162
Enrollment 66
Recruitment Details Participants were from China
Pre-assignment Details To enter the screening phase, the subjects' molecular alterations were determined using locally validated methodologies from a newly obtained tumor sample or the most recent archival tumor sample available. Based on the molecular alterations of the tumor, subjects were assigned to one of the treatment arms. Subjects with multiple molecular alterations in epidermal growth factor receptor and the relevant pathways were excluded, except under the conditions described in Inclusion criteria.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description Patient's tumor must have molecular alteration of the PIK3CA gene. Patient's tumor must have molecular alteration of the c-MET gene. Patient's tumor must have ALK or ROS1 gene rearrangement. Patient's tumor must have KRAS, NRAS or BRAF mutation.
Period Title: Overall Study
Started 2 16 26 22
Completed 0 0 6 0
Not Completed 2 16 20 22
Reason Not Completed
Death             1             0             0             2
Physician Decision             0             0             0             1
Progressive disease             1             13             12             14
Subject/guardian decision             0             1             0             3
Adverse Event             0             2             8             2
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID Total
Hide Arm/Group Description Patient's tumor must have molecular alteration of the PIK3CA gene. Patient's tumor must have molecular alteration of the c-MET gene. Patient's tumor must have ALK or ROS1 gene rearrangement. Patient's tumor must have KRAS, NRAS or BRAF mutation. Total of all reporting groups
Overall Number of Baseline Participants 2 16 26 22 66
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 2 participants 16 participants 26 participants 22 participants 66 participants
53.0
(44 to 62)
58.2
(47 to 65)
49.4
(33 to 66)
60.3
(48 to 74)
55.3
(33 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 16 participants 26 participants 22 participants 66 participants
Female
0
   0.0%
5
  31.3%
15
  57.7%
3
  13.6%
23
  34.8%
Male
2
 100.0%
11
  68.8%
11
  42.3%
19
  86.4%
43
  65.2%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description

Overall response rate is the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (Overall Response (OR) = CR + PR).

Complete Response (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 Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Time Frame Up to 231 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all subjects who received at least one dose of the respective study treatment.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 16 26 22
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3
  18.8%
19
  73.1%
2
   9.1%
2.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description OS is defined as the time from date of randomization/start of treatment to date of death due to any cause.
Time Frame Up to 231 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all subjects who received at least one dose of the respective study treatment.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 16 26 22
Median (95% Confidence Interval)
Unit of Measure: Months
4.99
(0.30 to 9.69)
13.26
(1.18 to 23.33)
NA [1] 
(19.35 to NA)
9.20
(3.52 to 11.93)
[1]
Median and upper limit NA because they are not evaluable. The median OS was not reached
3.Secondary Outcome
Title Number of Participants With Progression-free Survival (PFS)
Hide Description PFS event is defined as the first documented progression or death due to any cause according to RECIST 1.1 criteria
Time Frame Up to 231 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all subjects who received at least one dose of the respective study treatment.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 16 26 22
Measure Type: Count of Participants
Unit of Measure: Participants
2
 100.0%
16
 100.0%
19
  73.1%
19
  86.4%
4.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description

DCR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR) or Stable Disease (SD) according to RECIST 1.1 criteria (DCR: CR+PR+SD) Complete Response (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 Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD

Time Frame Up to 231 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all subjects who received at least one dose of the respective study treatment.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 16 26 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
50.0
(1.3 to 98.7)
43.8
(19.8 to 70.1)
92.3
(74.9 to 99.1)
59.1
(36.4 to 79.3)
5.Secondary Outcome
Title Median Duration of Overall Response (DOR)
Hide Description Duration of overall response (DOR) is defined as the time from the first documented CR or PR (confirmed by the subsequent assessment) to the date of the first documented progression or death due to underlying cancer.
Time Frame Up to 231 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set subjects with confirmed complete response (CR) or partial response (PR)
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 0 3 19 2
Median (95% Confidence Interval)
Unit of Measure: Months
3.84
(3.81 to 5.59)
34.96 [1] 
(7.59 to NA)
5.47
(3.55 to 7.39)
[1]
Upper limit NA because it is not evaluable
6.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description

Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to grades 1 - 4, was used.

Time Frame up to 235 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: Includes all patients who received at least one dose of the respective study medication and had at least one valid postbaseline safety assessment.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 16 26 22
Measure Type: Count of Participants
Unit of Measure: Participants
AE All grades
2
 100.0%
16
 100.0%
26
 100.0%
22
 100.0%
AE Grade 3/4
1
  50.0%
11
  68.8%
23
  88.5%
20
  90.9%
SAE All grades
1
  50.0%
12
  75.0%
11
  42.3%
18
  81.8%
SAE Grade 3/4
1
  50.0%
7
  43.8%
9
  34.6%
15
  68.2%
7.Secondary Outcome
Title Pharmacokinetics Profile, AUCtau and AUClast
Hide Description

PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

AUCtau is the AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1) AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

Time Frame Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PAS: Pharmacokinetic analysis set includes all subjects who have at least one blood sample providing evaluable PK data.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 14 6 9
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
AUClast Cycle 1 Day 1 Number Analyzed 2 participants 0 participants 0 participants 0 participants
20909  (107)
AUCtau Cycle 1 Day 15 Number Analyzed 1 participants 14 participants 6 participants 9 participants
23892 [1]   (NA) 32034  (6992) 30361  (3807) 2645  (981)
AUClast Cycle 1 Day 15 Number Analyzed 1 participants 14 participants 6 participants 9 participants
23721 [1]   (NA) 27875  (7629) 28013  (5006) 2642  (1026)
[1]
SD is NA since there is only 1 subject with evaluable PK profile
8.Secondary Outcome
Title Pharmacokinetics Profile, Cmax
Hide Description

PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

Cmax is the maximum (peak) observed plasma concentration (mass x volume-1) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

Time Frame Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PAS: Pharmacokinetic analysis set includes all subjects who have at least one blood sample providing evaluable PK data.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 14 6 9
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax Cycle 1 Day 1 Number Analyzed 2 participants 0 participants 0 participants 0 participants
2135  (700)
Cmax Cycle 1 Day 15 Number Analyzed 1 participants 14 participants 6 participants 9 participants
2630 [1]   (NA) 8046  (3550) 1362  (177) 587  (183)
[1]
SD is NA since there is only 1 subject with evaluable PK profile
9.Secondary Outcome
Title Pharmacokinetics Profile, Tmax
Hide Description

PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

Tmax is the time to reach maximum (peak) plasma concentration (time) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

Time Frame Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PAS: Pharmacokinetic analysis set includes all subjects who have at least one blood sample providing evaluable PK data.
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description:
Patient's tumor must have molecular alteration of the PIK3CA gene.
Patient's tumor must have molecular alteration of the c-MET gene.
Patient's tumor must have ALK or ROS1 gene rearrangement.
Patient's tumor must have KRAS, NRAS or BRAF mutation.
Overall Number of Participants Analyzed 2 14 6 9
Median (Full Range)
Unit of Measure: hours
Tmax Cycle 1 Day 1 Number Analyzed 2 participants 0 participants 0 participants 0 participants
4.03
(2.05 to 6.00)
Tmax Cycle 1 Day 15 Number Analyzed 1 participants 14 participants 6 participants 9 participants
2.00
(2.00 to 2.00)
1.00
(0.467 to 6.17)
6.10
(2.03 to 8.00)
1.10
(0.517 to 7.58)
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days after receiving the last dose of study treatment, up to maximum duration of 235 weeks.
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus 30 days after receiving the last dose of study treatment.
 
Arm/Group Title BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Hide Arm/Group Description Patient's tumor must have molecular alteration of the PIK3CA gene. Patient's tumor must have molecular alteration of the c-MET gene. Patient's tumor must have ALK or ROS1 gene rearrangement. Patient's tumor must have KRAS, NRAS or BRAF mutation.
All-Cause Mortality
BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/2 (50.00%)   4/16 (25.00%)   1/26 (3.85%)   5/22 (22.73%) 
Hide Serious Adverse Events
BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/2 (50.00%)   12/16 (75.00%)   11/26 (42.31%)   18/22 (81.82%) 
Blood and lymphatic system disorders         
Anaemia  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Cardiac disorders         
Rheumatic heart disease  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Gastrointestinal disorders         
Gastrointestinal haemorrhage  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
General disorders         
Asthenia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  1/22 (4.55%) 
Non-cardiac chest pain  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Pyrexia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  3/22 (13.64%) 
Hepatobiliary disorders         
Drug-induced liver injury  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Infections and infestations         
Appendicitis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Bronchitis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Pneumonia  1  0/2 (0.00%)  2/16 (12.50%)  3/26 (11.54%)  4/22 (18.18%) 
Pulmonary tuberculosis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Investigations         
Alanine aminotransferase increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Aspartate aminotransferase increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Blood alkaline phosphatase increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Blood creatine phosphokinase increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  4/22 (18.18%) 
Gamma-glutamyltransferase increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Hyperglycaemia  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Hyperuricaemia  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to bone  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Nervous system disorders         
Loss of consciousness  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Dyspnoea  1  1/2 (50.00%)  5/16 (31.25%)  1/26 (3.85%)  4/22 (18.18%) 
Interstitial lung disease  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  0/22 (0.00%) 
Pleural effusion  1  0/2 (0.00%)  2/16 (12.50%)  1/26 (3.85%)  3/22 (13.64%) 
Pulmonary embolism  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Vascular disorders         
Deep vein thrombosis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Venous thrombosis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
BYL719 350 mg QD INC280 400 mg BID Tab/600 mg BID Cap LDK378 750 mg QD MEK162 45 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/2 (100.00%)   16/16 (100.00%)   26/26 (100.00%)   22/22 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  0/2 (0.00%)  13/16 (81.25%)  19/26 (73.08%)  18/22 (81.82%) 
Leukocytosis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Leukopenia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Lymphopenia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Neutropenia  1  0/2 (0.00%)  1/16 (6.25%)  4/26 (15.38%)  0/22 (0.00%) 
Thrombocytopenia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  2/22 (9.09%) 
Cardiac disorders         
Atrial fibrillation  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Atrioventricular block first degree  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Atrioventricular dissociation  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Bradycardia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Bundle branch block right  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Nodal rhythm  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Palpitations  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  1/22 (4.55%) 
Pericardial effusion  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Sinus bradycardia  1  0/2 (0.00%)  0/16 (0.00%)  5/26 (19.23%)  0/22 (0.00%) 
Sinus tachycardia  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  2/22 (9.09%) 
Supraventricular extrasystoles  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Supraventricular tachycardia  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Tachycardia  1  1/2 (50.00%)  1/16 (6.25%)  1/26 (3.85%)  1/22 (4.55%) 
Ventricular extrasystoles  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Ventricular tachycardia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Wandering pacemaker  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Ear and labyrinth disorders         
Deafness unilateral  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Motion sickness  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Tinnitus  1  0/2 (0.00%)  0/16 (0.00%)  7/26 (26.92%)  0/22 (0.00%) 
Vertigo  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Eye disorders         
Cataract  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Eye disorder  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Eyelid oedema  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  1/22 (4.55%) 
Ocular discomfort  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Scleritis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Vision blurred  1  0/2 (0.00%)  0/16 (0.00%)  3/26 (11.54%)  2/22 (9.09%) 
Visual impairment  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Vitreous floaters  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Gastrointestinal disorders         
Abdominal discomfort  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  2/22 (9.09%) 
Abdominal distension  1  0/2 (0.00%)  0/16 (0.00%)  4/26 (15.38%)  2/22 (9.09%) 
Abdominal pain  1  0/2 (0.00%)  0/16 (0.00%)  11/26 (42.31%)  2/22 (9.09%) 
Abdominal pain lower  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  1/22 (4.55%) 
Abdominal pain upper  1  0/2 (0.00%)  2/16 (12.50%)  20/26 (76.92%)  3/22 (13.64%) 
Abnormal faeces  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Aphthous ulcer  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  3/22 (13.64%) 
Chronic gastritis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Constipation  1  0/2 (0.00%)  3/16 (18.75%)  4/26 (15.38%)  7/22 (31.82%) 
Diarrhoea  1  0/2 (0.00%)  4/16 (25.00%)  26/26 (100.00%)  14/22 (63.64%) 
Dry mouth  1  0/2 (0.00%)  0/16 (0.00%)  3/26 (11.54%)  5/22 (22.73%) 
Duodenal ulcer  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Dysphagia  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  2/22 (9.09%) 
Faeces hard  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Gastric dilatation  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Gingival bleeding  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Haemorrhoids  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Mouth ulceration  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  8/22 (36.36%) 
Nausea  1  0/2 (0.00%)  6/16 (37.50%)  12/26 (46.15%)  6/22 (27.27%) 
Oesophageal oedema  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Oesophagitis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Stomatitis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Toothache  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Vomiting  1  0/2 (0.00%)  6/16 (37.50%)  20/26 (76.92%)  9/22 (40.91%) 
General disorders         
Asthenia  1  0/2 (0.00%)  2/16 (12.50%)  10/26 (38.46%)  7/22 (31.82%) 
Chest discomfort  1  1/2 (50.00%)  5/16 (31.25%)  5/26 (19.23%)  2/22 (9.09%) 
Chills  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  1/22 (4.55%) 
Face oedema  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  5/22 (22.73%) 
Fatigue  1  0/2 (0.00%)  2/16 (12.50%)  3/26 (11.54%)  3/22 (13.64%) 
Impaired healing  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Influenza like illness  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Injection site swelling  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Malaise  1  1/2 (50.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Non-cardiac chest pain  1  0/2 (0.00%)  5/16 (31.25%)  12/26 (46.15%)  2/22 (9.09%) 
Oedema peripheral  1  0/2 (0.00%)  5/16 (31.25%)  4/26 (15.38%)  11/22 (50.00%) 
Pain  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  1/22 (4.55%) 
Pyrexia  1  0/2 (0.00%)  5/16 (31.25%)  7/26 (26.92%)  10/22 (45.45%) 
Sensation of foreign body  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Swelling face  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Immune system disorders         
Anaphylactic reaction  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  0/22 (0.00%) 
Infections and infestations         
Abscess  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Appendicitis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Cellulitis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Chronic sinusitis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Conjunctivitis  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Erythrasma  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Herpes zoster  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Nasopharyngitis  1  0/2 (0.00%)  0/16 (0.00%)  4/26 (15.38%)  0/22 (0.00%) 
Paronychia  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Pneumonia  1  0/2 (0.00%)  3/16 (18.75%)  2/26 (7.69%)  3/22 (13.64%) 
Respiratory tract infection  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Tonsillitis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Upper respiratory tract infection  1  0/2 (0.00%)  1/16 (6.25%)  5/26 (19.23%)  0/22 (0.00%) 
Urethritis  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Urinary tract infection  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Muscle strain  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Skin injury  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Wound complication  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Investigations         
Activated partial thromboplastin time prolonged  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  1/22 (4.55%) 
Alanine aminotransferase increased  1  0/2 (0.00%)  7/16 (43.75%)  24/26 (92.31%)  6/22 (27.27%) 
Albumin urine present  1  0/2 (0.00%)  3/16 (18.75%)  0/26 (0.00%)  0/22 (0.00%) 
Alpha hydroxybutyrate dehydrogenase increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Amylase increased  1  0/2 (0.00%)  7/16 (43.75%)  8/26 (30.77%)  6/22 (27.27%) 
Aspartate aminotransferase increased  1  1/2 (50.00%)  5/16 (31.25%)  26/26 (100.00%)  16/22 (72.73%) 
Bilirubin conjugated increased  1  0/2 (0.00%)  3/16 (18.75%)  7/26 (26.92%)  2/22 (9.09%) 
Blood albumin decreased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  2/22 (9.09%) 
Blood alkaline phosphatase increased  1  1/2 (50.00%)  5/16 (31.25%)  15/26 (57.69%)  6/22 (27.27%) 
Blood bilirubin increased  1  0/2 (0.00%)  5/16 (31.25%)  3/26 (11.54%)  3/22 (13.64%) 
Blood cholesterol increased  1  1/2 (50.00%)  2/16 (12.50%)  2/26 (7.69%)  0/22 (0.00%) 
Blood creatine increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Blood creatine phosphokinase MB increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Blood creatine phosphokinase increased  1  0/2 (0.00%)  2/16 (12.50%)  7/26 (26.92%)  16/22 (72.73%) 
Blood creatinine increased  1  1/2 (50.00%)  7/16 (43.75%)  10/26 (38.46%)  0/22 (0.00%) 
Blood fibrinogen increased  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  0/22 (0.00%) 
Blood glucose increased  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  2/22 (9.09%) 
Blood lactate dehydrogenase increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  2/22 (9.09%) 
Blood phosphorus decreased  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Blood pressure increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Blood triglycerides increased  1  1/2 (50.00%)  2/16 (12.50%)  4/26 (15.38%)  0/22 (0.00%) 
Blood urea increased  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Blood uric acid increased  1  0/2 (0.00%)  2/16 (12.50%)  2/26 (7.69%)  3/22 (13.64%) 
Electrocardiogram QT prolonged  1  0/2 (0.00%)  0/16 (0.00%)  10/26 (38.46%)  6/22 (27.27%) 
Electrocardiogram T wave abnormal  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Enzyme level increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Gamma-glutamyltransferase increased  1  1/2 (50.00%)  9/16 (56.25%)  15/26 (57.69%)  4/22 (18.18%) 
Glucose urine present  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  0/22 (0.00%) 
Haemoglobin increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
International normalised ratio increased  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  0/22 (0.00%) 
Lipase increased  1  0/2 (0.00%)  2/16 (12.50%)  5/26 (19.23%)  3/22 (13.64%) 
Neutrophil count decreased  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
PO2 decreased  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Platelet count decreased  1  0/2 (0.00%)  2/16 (12.50%)  0/26 (0.00%)  0/22 (0.00%) 
Platelet count increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Protein total decreased  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  3/22 (13.64%) 
Protein urine present  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  2/22 (9.09%) 
Prothrombin time prolonged  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  0/22 (0.00%) 
Red blood cell count decreased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Red blood cell count increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Red blood cells urine positive  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Thrombin time prolonged  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Troponin I increased  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  3/22 (13.64%) 
Weight decreased  1  0/2 (0.00%)  1/16 (6.25%)  15/26 (57.69%)  1/22 (4.55%) 
Weight increased  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
White blood cell count decreased  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  0/22 (0.00%) 
White blood cells urine positive  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Acidosis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Alkalosis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  1/22 (4.55%) 
Decreased appetite  1  0/2 (0.00%)  9/16 (56.25%)  14/26 (53.85%)  8/22 (36.36%) 
Diabetes mellitus  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Hypercholesterolaemia  1  0/2 (0.00%)  3/16 (18.75%)  4/26 (15.38%)  1/22 (4.55%) 
Hyperglycaemia  1  1/2 (50.00%)  5/16 (31.25%)  9/26 (34.62%)  1/22 (4.55%) 
Hyperkalaemia  1  0/2 (0.00%)  2/16 (12.50%)  1/26 (3.85%)  0/22 (0.00%) 
Hypermagnesaemia  1  1/2 (50.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Hypernatraemia  1  1/2 (50.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Hypertriglyceridaemia  1  0/2 (0.00%)  3/16 (18.75%)  7/26 (26.92%)  0/22 (0.00%) 
Hyperuricaemia  1  1/2 (50.00%)  5/16 (31.25%)  17/26 (65.38%)  4/22 (18.18%) 
Hypoalbuminaemia  1  2/2 (100.00%)  14/16 (87.50%)  21/26 (80.77%)  13/22 (59.09%) 
Hypocalcaemia  1  0/2 (0.00%)  4/16 (25.00%)  4/26 (15.38%)  8/22 (36.36%) 
Hypochloraemia  1  0/2 (0.00%)  2/16 (12.50%)  3/26 (11.54%)  2/22 (9.09%) 
Hypokalaemia  1  1/2 (50.00%)  2/16 (12.50%)  8/26 (30.77%)  5/22 (22.73%) 
Hypomagnesaemia  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Hyponatraemia  1  1/2 (50.00%)  6/16 (37.50%)  9/26 (34.62%)  10/22 (45.45%) 
Hypophosphataemia  1  1/2 (50.00%)  2/16 (12.50%)  8/26 (30.77%)  3/22 (13.64%) 
Hypoproteinaemia  1  0/2 (0.00%)  5/16 (31.25%)  4/26 (15.38%)  3/22 (13.64%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  2/22 (9.09%) 
Back pain  1  0/2 (0.00%)  2/16 (12.50%)  12/26 (46.15%)  2/22 (9.09%) 
Bone pain  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Muscle twitching  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Muscular weakness  1  0/2 (0.00%)  0/16 (0.00%)  4/26 (15.38%)  1/22 (4.55%) 
Musculoskeletal pain  1  0/2 (0.00%)  3/16 (18.75%)  3/26 (11.54%)  1/22 (4.55%) 
Musculoskeletal stiffness  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  2/22 (9.09%) 
Myalgia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  1/22 (4.55%) 
Neck pain  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  2/22 (9.09%) 
Pain in extremity  1  0/2 (0.00%)  3/16 (18.75%)  0/26 (0.00%)  1/22 (4.55%) 
Nervous system disorders         
Ageusia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Dizziness  1  0/2 (0.00%)  4/16 (25.00%)  9/26 (34.62%)  4/22 (18.18%) 
Dreamy state  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Dysgeusia  1  1/2 (50.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Headache  1  0/2 (0.00%)  2/16 (12.50%)  6/26 (23.08%)  0/22 (0.00%) 
Hypoaesthesia  1  0/2 (0.00%)  1/16 (6.25%)  3/26 (11.54%)  1/22 (4.55%) 
Intracranial pressure increased  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Neuralgia  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Paraesthesia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Seizure  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  0/22 (0.00%) 
Somnolence  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Speech disorder  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Taste disorder  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Psychiatric disorders         
Agitation  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Depression  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Dysphoria  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Insomnia  1  0/2 (0.00%)  1/16 (6.25%)  4/26 (15.38%)  2/22 (9.09%) 
Nervousness  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Tic  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Renal and urinary disorders         
Dysuria  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Pollakiuria  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Proteinuria  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Urinary retention  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Menstrual disorder  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Atelectasis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  1/22 (4.55%) 
Cough  1  1/2 (50.00%)  2/16 (12.50%)  17/26 (65.38%)  4/22 (18.18%) 
Dysphonia  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  2/22 (9.09%) 
Dyspnoea  1  0/2 (0.00%)  9/16 (56.25%)  6/26 (23.08%)  7/22 (31.82%) 
Dyspnoea exertional  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  2/22 (9.09%) 
Epistaxis  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  1/22 (4.55%) 
Haemoptysis  1  1/2 (50.00%)  3/16 (18.75%)  1/26 (3.85%)  3/22 (13.64%) 
Haemothorax  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Hiccups  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Interstitial lung disease  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Oropharyngeal discomfort  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Oropharyngeal pain  1  0/2 (0.00%)  1/16 (6.25%)  2/26 (7.69%)  1/22 (4.55%) 
Pharyngeal ulceration  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Pleural effusion  1  0/2 (0.00%)  3/16 (18.75%)  0/26 (0.00%)  1/22 (4.55%) 
Pneumonitis  1  1/2 (50.00%)  0/16 (0.00%)  0/26 (0.00%)  0/22 (0.00%) 
Productive cough  1  0/2 (0.00%)  5/16 (31.25%)  9/26 (34.62%)  3/22 (13.64%) 
Pulmonary arterial hypertension  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Respiratory failure  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Respiratory tract congestion  1  0/2 (0.00%)  0/16 (0.00%)  3/26 (11.54%)  0/22 (0.00%) 
Tachypnoea  1  0/2 (0.00%)  1/16 (6.25%)  1/26 (3.85%)  1/22 (4.55%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Hyperhidrosis  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Night sweats  1  0/2 (0.00%)  2/16 (12.50%)  1/26 (3.85%)  0/22 (0.00%) 
Pain of skin  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Pruritus  1  0/2 (0.00%)  3/16 (18.75%)  7/26 (26.92%)  4/22 (18.18%) 
Rash  1  0/2 (0.00%)  0/16 (0.00%)  12/26 (46.15%)  16/22 (72.73%) 
Skin exfoliation  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Skin fissures  1  0/2 (0.00%)  0/16 (0.00%)  0/26 (0.00%)  1/22 (4.55%) 
Skin hyperpigmentation  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Skin mass  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Vascular disorders         
Flushing  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Hypertension  1  0/2 (0.00%)  0/16 (0.00%)  2/26 (7.69%)  4/22 (18.18%) 
Hypotension  1  1/2 (50.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Hypovolaemic shock  1  0/2 (0.00%)  0/16 (0.00%)  1/26 (3.85%)  0/22 (0.00%) 
Shock  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
Superior vena cava syndrome  1  0/2 (0.00%)  1/16 (6.25%)  0/26 (0.00%)  0/22 (0.00%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
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 the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02276027    
Other Study ID Numbers: CINC280X2205
First Submitted: October 9, 2014
First Posted: October 27, 2014
Results First Submitted: October 14, 2020
Results First Posted: December 16, 2020
Last Update Posted: December 16, 2020