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
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02276027
Collaborator
(none)
66
1
4
56.8
1.2
Study Details
Study Description
Brief Summary
The purpose of this study was to evaluate the anti-tumor activity of single agent BYL719, INC280, LDK378 and MEK162 in advanced NSCLC patients carrying specific molecular alterations.
There is a great unmet medical need in NSCLC patients with advanced or metastatic disease. Novel approaches using targeted therapeutic agents for these patient populations with molecular characterization could potentially identify subsets of advanced NSCLC patients who would benefit from targeted kinase inhibition. Study treatments, BYL719, INC280, LDK378 and MEK162, which target PIK3CA, c-MET, ALK/ROS1 and MEK respectively, have shown promising data in either preclinical or clinical lung cancer settings.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
To enter the screening phase of the study, the subjects' molecular alterations were determined using locally validated methodologies from a newly obtained tumor sample (preferred) 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 (EGFR) and the relevant pathways were excluded, except under the conditions described in Inclusion criteria.
The treatment period began on Cycle 1 Day 1 and continued in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of informed consent, death or the subject transferred to another Novartis study that could continue to provide the study drug.
All subjects were required to be followed up for 30 days for safety after receiving the last dose of study treatment. Subjects who discontinued study treatment for any reason other than disease progression were followed up for progression of disease. All subjects were required to be followed for survival. For subjects transferred to another Novartis study, an end of treatment visit (EOT) was required to be performed and the subject would not enter the follow-up period.
Study Design
Study Type:
Interventional
Actual Enrollment
:
66 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Open Label, Multiple Arm Study of Single Agent AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Actual Study Start Date
:
Jan 20, 2015
Actual Primary Completion Date
:
Oct 15, 2019
Actual Study Completion Date
:
Oct 15, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BYL719 350 mg QD Patient's tumor must have molecular alteration of the PIK3CA gene. |
Drug: BYL719
BYL719 was dosed as 350 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take BYL719 exactly as prescribed.
|
| Experimental: INC280 400 mg BID tab/600 mg BID cap Patient's tumor must have molecular alteration of the c-MET gene. |
Drug: INC280
INC280 was dosed as 600 mg (tablet) or 400mg(Capsule) twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to takeINC280 exactly as prescribed.
|
| Experimental: LDK378 750 mg QD Patient's tumor must have ALK or ROS1 gene rearrangement. |
Drug: LDK378
LDK378 was dosed as 750 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take LDK378 exactly as prescribed.
|
| Experimental: MEK162 45 mg BID Patient's tumor must have KRAS, NRAS or BRAF mutation. |
Drug: MEK162
MEK162 was dosed as 45 mg twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take MEK162 exactly as prescribed.
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [Up to 231 weeks]
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.
Secondary Outcome Measures
- Median Overall Survival (OS) [Up to 231 weeks]
OS is defined as the time from date of randomization/start of treatment to date of death due to any cause.
- Number of Participants With Progression-free Survival (PFS) [Up to 231 weeks]
PFS event is defined as the first documented progression or death due to any cause according to RECIST 1.1 criteria
- Disease Control Rate (DCR) [Up to 231 weeks]
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
- Median Duration of Overall Response (DOR) [Up to 231 weeks]
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.
- Number of Participants With Adverse Events [up to 235 weeks]
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.
- Pharmacokinetics Profile, AUCtau and AUClast [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)]
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
- Pharmacokinetics Profile, Cmax [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)]
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
- Pharmacokinetics Profile, Tmax [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)]
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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Advanced (stage IIIB or stage IV) NSCLC
-
Must have specific molecular alterations
Exclusion Criteria:
-
Symptomatic central nervous system (CNS) metastases which are neurologically unstable or requiring increasing doses of steroids within the 4 weeks prior to study entry to control their CNS disease
-
Radiation therapy within ≤ 4 weeks prior to study entry, with the exception of limited field palliative radiotherapy for bone pain relief.
-
Any other malignancies within the last 5 years before study entry
-
Major surgery ≤ 2 weeks prior to study entry or who have not recovered from side effects of such therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Guangzhou | Guangdong | China | 51000 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02276027
Other Study ID Numbers:
- CINC280X2205
First Posted:
Oct 27, 2014
Last Update Posted:
Dec 16, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were from China |
|---|---|
| Pre-assignment Detail | 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 |
|---|---|---|---|---|
| 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 |
Baseline Characteristics
| 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 |
|---|---|---|---|---|---|
| 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 Participants | 2 | 16 | 26 | 22 | 66 |
| Age (years) [Mean (Inter-Quartile Range) ] | |||||
| Mean (Inter-Quartile Range) [years] |
53.0
|
58.2
|
49.4
|
60.3
|
55.3
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
5
31.3%
|
15
57.7%
|
3
13.6%
|
23
34.8%
|
| Male |
2
100%
|
11
68.8%
|
11
42.3%
|
19
86.4%
|
43
65.2%
|
| Race and Ethnicity Not Collected (Count of Participants) | |||||
| Count of Participants [Participants] |
0
0%
|
||||
Outcome Measures
| Title | Overall Response Rate (ORR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 16 | 26 | 22 |
| Count of Participants [Participants] |
0
0%
|
3
18.8%
|
19
73.1%
|
2
9.1%
|
| Title | Median Overall Survival (OS) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 16 | 26 | 22 |
| Median (95% Confidence Interval) [Months] |
4.99
|
13.26
|
NA
|
9.20
|
| Title | Number of Participants With Progression-free Survival (PFS) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 16 | 26 | 22 |
| Count of Participants [Participants] |
2
100%
|
16
100%
|
19
73.1%
|
19
86.4%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 16 | 26 | 22 |
| Number (95% Confidence Interval) [Percentage of participants] |
50.0
2500%
|
43.8
273.8%
|
92.3
355%
|
59.1
268.6%
|
| Title | Median Duration of Overall Response (DOR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 0 | 3 | 19 | 2 |
| Median (95% Confidence Interval) [Months] |
3.84
|
34.96
|
5.47
|
| Title | Number of Participants With Adverse Events |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 16 | 26 | 22 |
| AE All grades |
2
100%
|
16
100%
|
26
100%
|
22
100%
|
| AE Grade 3/4 |
1
50%
|
11
68.8%
|
23
88.5%
|
20
90.9%
|
| SAE All grades |
1
50%
|
12
75%
|
11
42.3%
|
18
81.8%
|
| SAE Grade 3/4 |
1
50%
|
7
43.8%
|
9
34.6%
|
15
68.2%
|
| Title | Pharmacokinetics Profile, AUCtau and AUClast |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 14 | 6 | 9 |
| AUClast Cycle 1 Day 1 |
20909
(107)
|
|||
| AUCtau Cycle 1 Day 15 |
23892
(NA)
|
32034
(6992)
|
30361
(3807)
|
2645
(981)
|
| AUClast Cycle 1 Day 15 |
23721
(NA)
|
27875
(7629)
|
28013
(5006)
|
2642
(1026)
|
| Title | Pharmacokinetics Profile, Cmax |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 14 | 6 | 9 |
| Cmax Cycle 1 Day 1 |
2135
(700)
|
|||
| Cmax Cycle 1 Day 15 |
2630
(NA)
|
8046
(3550)
|
1362
(177)
|
587
(183)
|
| Title | Pharmacokinetics Profile, Tmax |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 2 | 14 | 6 | 9 |
| Tmax Cycle 1 Day 1 |
4.03
|
|||
| Tmax Cycle 1 Day 15 |
2.00
|
1.00
|
6.10
|
1.10
|
Adverse Events
| 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 | ||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/2 (50%) | 4/16 (25%) | 1/26 (3.8%) | 5/22 (22.7%) | ||||
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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/2 (50%) | 12/16 (75%) | 11/26 (42.3%) | 18/22 (81.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Cardiac disorders | ||||||||
| Rheumatic heart disease | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Gastrointestinal haemorrhage | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| General disorders | ||||||||
| Asthenia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Non-cardiac chest pain | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Pyrexia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 3/22 (13.6%) | ||||
| Hepatobiliary disorders | ||||||||
| Drug-induced liver injury | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Bronchitis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Pneumonia | 0/2 (0%) | 2/16 (12.5%) | 3/26 (11.5%) | 4/22 (18.2%) | ||||
| Pulmonary tuberculosis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Aspartate aminotransferase increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Blood alkaline phosphatase increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Blood creatine phosphokinase increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 4/22 (18.2%) | ||||
| Gamma-glutamyltransferase increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperglycaemia | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Hyperuricaemia | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Metastases to bone | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Nervous system disorders | ||||||||
| Loss of consciousness | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Atelectasis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Dyspnoea | 1/2 (50%) | 5/16 (31.3%) | 1/26 (3.8%) | 4/22 (18.2%) | ||||
| Interstitial lung disease | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Pleural effusion | 0/2 (0%) | 2/16 (12.5%) | 1/26 (3.8%) | 3/22 (13.6%) | ||||
| Pulmonary embolism | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Venous thrombosis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
Other (Not Including 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 16/16 (100%) | 26/26 (100%) | 22/22 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/2 (0%) | 13/16 (81.3%) | 19/26 (73.1%) | 18/22 (81.8%) | ||||
| Leukocytosis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Leukopenia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Lymphopenia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Neutropenia | 0/2 (0%) | 1/16 (6.3%) | 4/26 (15.4%) | 0/22 (0%) | ||||
| Thrombocytopenia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Atrioventricular block first degree | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Atrioventricular dissociation | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Bradycardia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Bundle branch block right | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Nodal rhythm | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Palpitations | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 1/22 (4.5%) | ||||
| Pericardial effusion | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Sinus bradycardia | 0/2 (0%) | 0/16 (0%) | 5/26 (19.2%) | 0/22 (0%) | ||||
| Sinus tachycardia | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Supraventricular extrasystoles | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Supraventricular tachycardia | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Tachycardia | 1/2 (50%) | 1/16 (6.3%) | 1/26 (3.8%) | 1/22 (4.5%) | ||||
| Ventricular extrasystoles | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Ventricular tachycardia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Wandering pacemaker | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness unilateral | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Motion sickness | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Tinnitus | 0/2 (0%) | 0/16 (0%) | 7/26 (26.9%) | 0/22 (0%) | ||||
| Vertigo | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Eye disorder | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Eyelid oedema | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 1/22 (4.5%) | ||||
| Ocular discomfort | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Scleritis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Vision blurred | 0/2 (0%) | 0/16 (0%) | 3/26 (11.5%) | 2/22 (9.1%) | ||||
| Visual impairment | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Vitreous floaters | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 2/22 (9.1%) | ||||
| Abdominal distension | 0/2 (0%) | 0/16 (0%) | 4/26 (15.4%) | 2/22 (9.1%) | ||||
| Abdominal pain | 0/2 (0%) | 0/16 (0%) | 11/26 (42.3%) | 2/22 (9.1%) | ||||
| Abdominal pain lower | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 1/22 (4.5%) | ||||
| Abdominal pain upper | 0/2 (0%) | 2/16 (12.5%) | 20/26 (76.9%) | 3/22 (13.6%) | ||||
| Abnormal faeces | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Aphthous ulcer | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 3/22 (13.6%) | ||||
| Chronic gastritis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Constipation | 0/2 (0%) | 3/16 (18.8%) | 4/26 (15.4%) | 7/22 (31.8%) | ||||
| Diarrhoea | 0/2 (0%) | 4/16 (25%) | 26/26 (100%) | 14/22 (63.6%) | ||||
| Dry mouth | 0/2 (0%) | 0/16 (0%) | 3/26 (11.5%) | 5/22 (22.7%) | ||||
| Duodenal ulcer | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Dysphagia | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Faeces hard | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Gastric dilatation | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Gingival bleeding | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Haemorrhoids | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Mouth ulceration | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 8/22 (36.4%) | ||||
| Nausea | 0/2 (0%) | 6/16 (37.5%) | 12/26 (46.2%) | 6/22 (27.3%) | ||||
| Oesophageal oedema | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Oesophagitis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Stomatitis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Toothache | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Vomiting | 0/2 (0%) | 6/16 (37.5%) | 20/26 (76.9%) | 9/22 (40.9%) | ||||
| General disorders | ||||||||
| Asthenia | 0/2 (0%) | 2/16 (12.5%) | 10/26 (38.5%) | 7/22 (31.8%) | ||||
| Chest discomfort | 1/2 (50%) | 5/16 (31.3%) | 5/26 (19.2%) | 2/22 (9.1%) | ||||
| Chills | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 1/22 (4.5%) | ||||
| Face oedema | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 5/22 (22.7%) | ||||
| Fatigue | 0/2 (0%) | 2/16 (12.5%) | 3/26 (11.5%) | 3/22 (13.6%) | ||||
| Impaired healing | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Influenza like illness | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Injection site swelling | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Malaise | 1/2 (50%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Non-cardiac chest pain | 0/2 (0%) | 5/16 (31.3%) | 12/26 (46.2%) | 2/22 (9.1%) | ||||
| Oedema peripheral | 0/2 (0%) | 5/16 (31.3%) | 4/26 (15.4%) | 11/22 (50%) | ||||
| Pain | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 1/22 (4.5%) | ||||
| Pyrexia | 0/2 (0%) | 5/16 (31.3%) | 7/26 (26.9%) | 10/22 (45.5%) | ||||
| Sensation of foreign body | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Swelling face | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Immune system disorders | ||||||||
| Anaphylactic reaction | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Infections and infestations | ||||||||
| Abscess | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Appendicitis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Cellulitis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Chronic sinusitis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Conjunctivitis | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Erythrasma | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Herpes zoster | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Nasopharyngitis | 0/2 (0%) | 0/16 (0%) | 4/26 (15.4%) | 0/22 (0%) | ||||
| Paronychia | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Pneumonia | 0/2 (0%) | 3/16 (18.8%) | 2/26 (7.7%) | 3/22 (13.6%) | ||||
| Respiratory tract infection | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Tonsillitis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Upper respiratory tract infection | 0/2 (0%) | 1/16 (6.3%) | 5/26 (19.2%) | 0/22 (0%) | ||||
| Urethritis | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Urinary tract infection | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Muscle strain | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Skin injury | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Wound complication | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Alanine aminotransferase increased | 0/2 (0%) | 7/16 (43.8%) | 24/26 (92.3%) | 6/22 (27.3%) | ||||
| Albumin urine present | 0/2 (0%) | 3/16 (18.8%) | 0/26 (0%) | 0/22 (0%) | ||||
| Alpha hydroxybutyrate dehydrogenase increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Amylase increased | 0/2 (0%) | 7/16 (43.8%) | 8/26 (30.8%) | 6/22 (27.3%) | ||||
| Aspartate aminotransferase increased | 1/2 (50%) | 5/16 (31.3%) | 26/26 (100%) | 16/22 (72.7%) | ||||
| Bilirubin conjugated increased | 0/2 (0%) | 3/16 (18.8%) | 7/26 (26.9%) | 2/22 (9.1%) | ||||
| Blood albumin decreased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 2/22 (9.1%) | ||||
| Blood alkaline phosphatase increased | 1/2 (50%) | 5/16 (31.3%) | 15/26 (57.7%) | 6/22 (27.3%) | ||||
| Blood bilirubin increased | 0/2 (0%) | 5/16 (31.3%) | 3/26 (11.5%) | 3/22 (13.6%) | ||||
| Blood cholesterol increased | 1/2 (50%) | 2/16 (12.5%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Blood creatine increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Blood creatine phosphokinase MB increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Blood creatine phosphokinase increased | 0/2 (0%) | 2/16 (12.5%) | 7/26 (26.9%) | 16/22 (72.7%) | ||||
| Blood creatinine increased | 1/2 (50%) | 7/16 (43.8%) | 10/26 (38.5%) | 0/22 (0%) | ||||
| Blood fibrinogen increased | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 0/22 (0%) | ||||
| Blood glucose increased | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Blood lactate dehydrogenase increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 2/22 (9.1%) | ||||
| Blood phosphorus decreased | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Blood pressure increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Blood triglycerides increased | 1/2 (50%) | 2/16 (12.5%) | 4/26 (15.4%) | 0/22 (0%) | ||||
| Blood urea increased | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Blood uric acid increased | 0/2 (0%) | 2/16 (12.5%) | 2/26 (7.7%) | 3/22 (13.6%) | ||||
| Electrocardiogram QT prolonged | 0/2 (0%) | 0/16 (0%) | 10/26 (38.5%) | 6/22 (27.3%) | ||||
| Electrocardiogram T wave abnormal | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Enzyme level increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Gamma-glutamyltransferase increased | 1/2 (50%) | 9/16 (56.3%) | 15/26 (57.7%) | 4/22 (18.2%) | ||||
| Glucose urine present | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 0/22 (0%) | ||||
| Haemoglobin increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| International normalised ratio increased | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Lipase increased | 0/2 (0%) | 2/16 (12.5%) | 5/26 (19.2%) | 3/22 (13.6%) | ||||
| Neutrophil count decreased | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| PO2 decreased | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Platelet count decreased | 0/2 (0%) | 2/16 (12.5%) | 0/26 (0%) | 0/22 (0%) | ||||
| Platelet count increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Protein total decreased | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 3/22 (13.6%) | ||||
| Protein urine present | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 2/22 (9.1%) | ||||
| Prothrombin time prolonged | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Red blood cell count decreased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Red blood cell count increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Red blood cells urine positive | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Thrombin time prolonged | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Troponin I increased | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 3/22 (13.6%) | ||||
| Weight decreased | 0/2 (0%) | 1/16 (6.3%) | 15/26 (57.7%) | 1/22 (4.5%) | ||||
| Weight increased | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| White blood cell count decreased | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| White blood cells urine positive | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Alkalosis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Decreased appetite | 0/2 (0%) | 9/16 (56.3%) | 14/26 (53.8%) | 8/22 (36.4%) | ||||
| Diabetes mellitus | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Hypercholesterolaemia | 0/2 (0%) | 3/16 (18.8%) | 4/26 (15.4%) | 1/22 (4.5%) | ||||
| Hyperglycaemia | 1/2 (50%) | 5/16 (31.3%) | 9/26 (34.6%) | 1/22 (4.5%) | ||||
| Hyperkalaemia | 0/2 (0%) | 2/16 (12.5%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Hypermagnesaemia | 1/2 (50%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Hypernatraemia | 1/2 (50%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Hypertriglyceridaemia | 0/2 (0%) | 3/16 (18.8%) | 7/26 (26.9%) | 0/22 (0%) | ||||
| Hyperuricaemia | 1/2 (50%) | 5/16 (31.3%) | 17/26 (65.4%) | 4/22 (18.2%) | ||||
| Hypoalbuminaemia | 2/2 (100%) | 14/16 (87.5%) | 21/26 (80.8%) | 13/22 (59.1%) | ||||
| Hypocalcaemia | 0/2 (0%) | 4/16 (25%) | 4/26 (15.4%) | 8/22 (36.4%) | ||||
| Hypochloraemia | 0/2 (0%) | 2/16 (12.5%) | 3/26 (11.5%) | 2/22 (9.1%) | ||||
| Hypokalaemia | 1/2 (50%) | 2/16 (12.5%) | 8/26 (30.8%) | 5/22 (22.7%) | ||||
| Hypomagnesaemia | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Hyponatraemia | 1/2 (50%) | 6/16 (37.5%) | 9/26 (34.6%) | 10/22 (45.5%) | ||||
| Hypophosphataemia | 1/2 (50%) | 2/16 (12.5%) | 8/26 (30.8%) | 3/22 (13.6%) | ||||
| Hypoproteinaemia | 0/2 (0%) | 5/16 (31.3%) | 4/26 (15.4%) | 3/22 (13.6%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 2/22 (9.1%) | ||||
| Back pain | 0/2 (0%) | 2/16 (12.5%) | 12/26 (46.2%) | 2/22 (9.1%) | ||||
| Bone pain | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Muscle twitching | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Muscular weakness | 0/2 (0%) | 0/16 (0%) | 4/26 (15.4%) | 1/22 (4.5%) | ||||
| Musculoskeletal pain | 0/2 (0%) | 3/16 (18.8%) | 3/26 (11.5%) | 1/22 (4.5%) | ||||
| Musculoskeletal stiffness | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 2/22 (9.1%) | ||||
| Myalgia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 1/22 (4.5%) | ||||
| Neck pain | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 2/22 (9.1%) | ||||
| Pain in extremity | 0/2 (0%) | 3/16 (18.8%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Nervous system disorders | ||||||||
| Ageusia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Dizziness | 0/2 (0%) | 4/16 (25%) | 9/26 (34.6%) | 4/22 (18.2%) | ||||
| Dreamy state | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Dysgeusia | 1/2 (50%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Headache | 0/2 (0%) | 2/16 (12.5%) | 6/26 (23.1%) | 0/22 (0%) | ||||
| Hypoaesthesia | 0/2 (0%) | 1/16 (6.3%) | 3/26 (11.5%) | 1/22 (4.5%) | ||||
| Intracranial pressure increased | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Neuralgia | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Paraesthesia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Seizure | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 0/22 (0%) | ||||
| Somnolence | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Speech disorder | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Taste disorder | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Depression | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Dysphoria | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Insomnia | 0/2 (0%) | 1/16 (6.3%) | 4/26 (15.4%) | 2/22 (9.1%) | ||||
| Nervousness | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Tic | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Pollakiuria | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Proteinuria | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Urinary retention | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Menstrual disorder | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Atelectasis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Cough | 1/2 (50%) | 2/16 (12.5%) | 17/26 (65.4%) | 4/22 (18.2%) | ||||
| Dysphonia | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 2/22 (9.1%) | ||||
| Dyspnoea | 0/2 (0%) | 9/16 (56.3%) | 6/26 (23.1%) | 7/22 (31.8%) | ||||
| Dyspnoea exertional | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 2/22 (9.1%) | ||||
| Epistaxis | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 1/22 (4.5%) | ||||
| Haemoptysis | 1/2 (50%) | 3/16 (18.8%) | 1/26 (3.8%) | 3/22 (13.6%) | ||||
| Haemothorax | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Hiccups | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Interstitial lung disease | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Oropharyngeal discomfort | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Oropharyngeal pain | 0/2 (0%) | 1/16 (6.3%) | 2/26 (7.7%) | 1/22 (4.5%) | ||||
| Pharyngeal ulceration | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Pleural effusion | 0/2 (0%) | 3/16 (18.8%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Pneumonitis | 1/2 (50%) | 0/16 (0%) | 0/26 (0%) | 0/22 (0%) | ||||
| Productive cough | 0/2 (0%) | 5/16 (31.3%) | 9/26 (34.6%) | 3/22 (13.6%) | ||||
| Pulmonary arterial hypertension | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Respiratory failure | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Respiratory tract congestion | 0/2 (0%) | 0/16 (0%) | 3/26 (11.5%) | 0/22 (0%) | ||||
| Tachypnoea | 0/2 (0%) | 1/16 (6.3%) | 1/26 (3.8%) | 1/22 (4.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Hyperhidrosis | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Night sweats | 0/2 (0%) | 2/16 (12.5%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Pain of skin | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Pruritus | 0/2 (0%) | 3/16 (18.8%) | 7/26 (26.9%) | 4/22 (18.2%) | ||||
| Rash | 0/2 (0%) | 0/16 (0%) | 12/26 (46.2%) | 16/22 (72.7%) | ||||
| Skin exfoliation | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Skin fissures | 0/2 (0%) | 0/16 (0%) | 0/26 (0%) | 1/22 (4.5%) | ||||
| Skin hyperpigmentation | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Skin mass | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Vascular disorders | ||||||||
| Flushing | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Hypertension | 0/2 (0%) | 0/16 (0%) | 2/26 (7.7%) | 4/22 (18.2%) | ||||
| Hypotension | 1/2 (50%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Hypovolaemic shock | 0/2 (0%) | 0/16 (0%) | 1/26 (3.8%) | 0/22 (0%) | ||||
| Shock | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
| Superior vena cava syndrome | 0/2 (0%) | 1/16 (6.3%) | 0/26 (0%) | 0/22 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02276027
Other Study ID Numbers:
- CINC280X2205
First Posted:
Oct 27, 2014
Last Update Posted:
Dec 16, 2020
Last Verified:
Nov 1, 2020