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Selinexor (KPT-330) in Older Patients With Relapsed AML (SOPRA)

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ClinicalTrials.gov Identifier: NCT02088541
Recruitment Status : Completed
First Posted : March 17, 2014
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia (AML)
Interventions Drug: Selinexor
Drug: Hydroxyurea
Drug: Ara-C
Enrollment 317
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2) Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description Participants under protocol versions (PV) less than (<) 5.0 (those who had one prior line of acute myeloid leukemia (AML) therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (milligrams per square meter) (60 to 120 mg based on body surface area [BSA]) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV greater than or equal to (>=) 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Period Title: Overall Study
Started 71 27 117 44 58
Safety Population 71 27 115 39 45
Intent-to-treat (ITT) Population 0 0 118 [1] 0 57
Completed 0 0 0 0 0
Not Completed 71 27 117 44 58
Reason Not Completed
Adverse Event             3             0             3             3             0
Death             51             21             85             28             38
Lost to Follow-up             2             0             1             0             0
Physician Decision             2             1             2             0             2
Disease progression             7             1             2             3             1
Study terminated by sponsor             1             1             12             2             6
Withdrawal by Subject             3             2             9             7             10
Other             2             1             3             1             1
[1]
1 randomized to Selinexor 60mg (PV>=5) but treated with physician choice 2, counted under this arm.
Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60 mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5) Total
Hide Arm/Group Description Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (60 to 120 mg based on BSA) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals. Total of all reporting groups
Overall Number of Baseline Participants 71 27 115 39 45 297
Hide Baseline Analysis Population Description
Safety Population included all participants who received any amount of study treatment and was the primary population for the analysis of safety outcome measure.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 27 participants 115 participants 39 participants 45 participants 297 participants
72.4  (6.49) 73.2  (4.64) 73.6  (5.99) 72.6  (5.24) 74.2  (5.92) 73.2  (5.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 27 participants 115 participants 39 participants 45 participants 297 participants
Female
26
  36.6%
11
  40.7%
46
  40.0%
17
  43.6%
15
  33.3%
115
  38.7%
Male
45
  63.4%
16
  59.3%
69
  60.0%
22
  56.4%
30
  66.7%
182
  61.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 27 participants 115 participants 39 participants 45 participants 297 participants
Hispanic or Latino
4
   5.6%
3
  11.1%
9
   7.8%
4
  10.3%
6
  13.3%
26
   8.8%
Not Hispanic or Latino
65
  91.5%
23
  85.2%
93
  80.9%
34
  87.2%
31
  68.9%
246
  82.8%
Unknown or Not Reported
2
   2.8%
1
   3.7%
13
  11.3%
1
   2.6%
8
  17.8%
25
   8.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 71 participants 27 participants 115 participants 39 participants 45 participants 297 participants
White 67 22 95 39 37 260
Black or African American 3 1 3 0 0 7
Asian 0 2 0 0 0 2
Other 0 1 15 0 6 22
Unknown 1 1 2 0 2 6
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Median (95% Confidence Interval)
Unit of Measure: Days
94.0
(78.0 to 158.0)
170.0
(111.0 to 220.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4221
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.79 to 1.75
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
Hide Description Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Time Frame From randomization (Day 1) up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV >=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
53.49
(43.54 to 62.44)
70.73
(55.60 to 81.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9464
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
Hide Description CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.1
(1.9 to 10.7)
0
(0.0 to 6.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0986
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
Hide Description DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population:all participants who randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. This outcome measure(OM) was only defined for CR participants. For Physician Choice 2,there was zero CR participants."Overall Number of Participants Analyzed (N)": Number of participants evaluable for this OM.
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5, received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 6 0
Median (95% Confidence Interval)
Unit of Measure: Days
121.0 [1] 
(49.0 to NA)
[1]
Upper limits of 95% confidence Interval (CI) was not estimable due to less number of participants and events.
5.Secondary Outcome
Title Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
Hide Description mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
11.9
(6.6 to 19.1)
3.5
(0.4 to 12.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0844
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
6.Secondary Outcome
Title Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission or CR With Incomplete Hematologic Recovery (CRi) or Complete Remission With Incomplete Platelet Recovery (CRp)
Hide Description DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV >=5.0, regardless of whether or not they received study treatment. Here, "N" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5, received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 14 2
Median (95% Confidence Interval)
Unit of Measure: Days
175.0
(61.0 to 288.0)
106.0 [1] 
(NA to NA)
[1]
Upper and lower limits of 95% CI was not estimable due to the small number of participants and events.
7.Secondary Outcome
Title Percentage of Participants With Overall Response Rate (ORR)
Hide Description Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
13.6
(8.0 to 21.1)
8.8
(2.9 to 19.3)
8.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.
Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. Here, "N" signifies number of participants evaluable for this outcome measure.
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 16 5
Median (95% Confidence Interval)
Unit of Measure: Days
204.0
(117.0 to 334.0)
148.0 [1] 
(85.0 to NA)
[1]
Upper limit of 95% CI was not estimated due to less number of participants and events.
9.Secondary Outcome
Title Percentage of Participants With Disease Control Rate (DCR)
Hide Description DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks.
Time Frame Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 118 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
50.8
(41.5 to 60.2)
40.4
(27.6 to 54.2)
10.Secondary Outcome
Title Duration of Disease Control Rate
Hide Description Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks.
Time Frame Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
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ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. Here," N" signifies number of participants evaluable for this measure.
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
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Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 60 23
Median (95% Confidence Interval)
Unit of Measure: Days
187.0
(125.0 to 261.0)
233.0
(155.0 to 263.0)
11.Secondary Outcome
Title Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
Hide Description QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.
Time Frame Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
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Per-Protocol (PP) population: all participants randomized to study treatment under PV>=5.0 who received any amount of study treatment and had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n=participants evaluable for this outcome measure at specified categories.
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 71 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Number Analyzed 65 participants 29 participants
70.5  (15.20) 75.4  (14.74)
C2D1 Number Analyzed 59 participants 25 participants
0.5  (16.50) -1.9  (15.18)
C3D1 Number Analyzed 39 participants 16 participants
-1.9  (16.88) -5.4  (22.25)
C4D1 Number Analyzed 26 participants 7 participants
-1.2  (15.70) -7.4  (25.41)
C5D1 Number Analyzed 20 participants 7 participants
-2.4  (16.84) 1.9  (8.40)
C6D1 Number Analyzed 19 participants 6 participants
-3.4  (15.66) -4.7  (13.20)
C7D1 Number Analyzed 15 participants 5 participants
-5.0  (17.21) -11.8  (27.43)
C8D1 Number Analyzed 15 participants 5 participants
-3.9  (15.78) -10.6  (7.83)
C9D1 Number Analyzed 11 participants 4 participants
-2.7  (7.47) -8.0  (8.49)
C10D1 Number Analyzed 9 participants 3 participants
2.4  (13.19) -10.7  (12.70)
C11D1 Number Analyzed 7 participants 2 participants
-0.1  (8.65) -10.0  (9.90)
C12D1 Number Analyzed 6 participants 2 participants
-3.7  (11.69) -7.0  (16.97)
C13D1 Number Analyzed 4 participants 1 participants
-3.3  (6.40) -9.0 [1]   (NA)
C14D1 Number Analyzed 3 participants 1 participants
-4.0  (3.46) -15.0
C15D1 Number Analyzed 2 participants 1 participants
1.5  (3.54) -10.0 [1]   (NA)
C16D1 Number Analyzed 0 participants 1 participants
-15.0 [1]   (NA)
C17D1 Number Analyzed 1 participants 1 participants
-15.0 [1]   (NA) -7.0 [1]   (NA)
C18D1 Number Analyzed 1 participants 0 participants
-1.0 [1]   (NA)
C19D1 Number Analyzed 1 participants 0 participants
-12.0 [1]   (NA)
C20D1 Number Analyzed 1 participants 0 participants
-14.0 [1]   (NA)
Final visit Number Analyzed 25 participants 12 participants
2.5  (17.71) -1.7  (20.46)
[1]
Standard Deviation was not estimated due to less number of participants.
12.Secondary Outcome
Title Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
Hide Description EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
Time Frame Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
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Hide Analysis Population Description
PP Population included all participants randomized to study treatment under PV >=5.0 who received any amount of study treatment and who had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n =Participants evaluable for this outcome measure at specified categories
Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description:
Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle).
Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
Overall Number of Participants Analyzed 71 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Number Analyzed 59 participants 30 participants
67.9  (19.51) 63.5  (21.10)
C2D1 Number Analyzed 51 participants 25 participants
-7.5  (23.45) 0.8  (15.82)
C3D1 Number Analyzed 35 participants 17 participants
-13.3  (25.04) -5.2  (23.54)
C4D1 Number Analyzed 23 participants 9 participants
-6.1  (20.80) -5.0  (11.46)
C5D1 Number Analyzed 18 participants 10 participants
-0.9  (20.83) -2.0  (15.31)
C6D1 Number Analyzed 17 participants 7 participants
-11.2  (25.90) -1.4  (24.10)
C7D1 Number Analyzed 14 participants 5 participants
-3.7  (23.91) 4.0  (10.84)
C8D1 Number Analyzed 13 participants 5 participants
0.1  (16.77) 5.0  (9.35)
C9D1 Number Analyzed 9 participants 4 participants
4.6  (13.25) 5.0  (10.80)
C10D1 Number Analyzed 7 participants 4 participants
0.7  (18.58) 6.3  (15.48)
C11D1 Number Analyzed 6 participants 2 participants
0.8  (18.55) -5.0  (21.21)
C12D1 Number Analyzed 6 participants 2 participants
3.3  (16.63) -5.0  (28.28)
C13D1 Number Analyzed 3 participants 1 participants
6.7  (20.21) 10.0 [1]   (NA)
C14D1 Number Analyzed 3 participants 1 participants
6.7  (25.66) 15.0 [1]   (NA)
C15D1 Number Analyzed 2 participants 1 participants
3.5  (30.41) -10.0 [1]   (NA)
C16D1 Number Analyzed 0 participants 1 participants
20.0 [1]   (NA)
C17D1 Number Analyzed 1 participants 1 participants
25.0 [1]   (NA) -5.0 [1]   (NA)
C18D1 Number Analyzed 1 participants 0 participants
25.0 [1]   (NA)
C19D1 Number Analyzed 1 participants 0 participants
30.0 [1]   (NA)
C20D1 Number Analyzed 1 participants 0 participants
35.0 [1]   (NA)
[1]
Standard Deviation was not estimated due to less number of participants.
Time Frame From start of study drug administration to 30 days after last dose of study drug (approximately 48 months)
Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
 
Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
Hide Arm/Group Description Participants under PV <5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (60 to 120 mg based on BSA) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV <5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
All-Cause Mortality
Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/71 (33.80%)      3/27 (11.11%)      28/115 (24.35%)      7/39 (17.95%)      9/45 (20.00%)    
Hide Serious Adverse Events
Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/71 (81.69%)      15/27 (55.56%)      89/115 (77.39%)      25/39 (64.10%)      30/45 (66.67%)    
Blood and lymphatic system disorders           
Anaemia * 1  2/71 (2.82%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  3/45 (6.67%) 
Febrile Neutropenia * 1  16/71 (22.54%)  4/27 (14.81%)  20/115 (17.39%)  8/39 (20.51%)  16/45 (35.56%) 
Leukostasis Syndrome * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Neutropenia * 1  1/71 (1.41%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Splenic Infarction * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Thrombocytopenia * 1  1/71 (1.41%)  1/27 (3.70%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cardiac disorders           
Acute Coronary Syndrome * 1  0/71 (0.00%)  1/27 (3.70%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Atrial Fibrillation * 1  2/71 (2.82%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Bradycardia * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cardiac Failure * 1  1/71 (1.41%)  0/27 (0.00%)  3/115 (2.61%)  0/39 (0.00%)  0/45 (0.00%) 
Cardiac Failure Congestive * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cardio-Respiratory Arrest * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Sinus Bradycardia * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Tachyarrhythmia * 1  0/71 (0.00%)  1/27 (3.70%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Ventricular Fibrillation * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Ear and labyrinth disorders           
Vertigo * 1  0/71 (0.00%)  1/27 (3.70%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Eye disorders           
Cataract * 1  0/71 (0.00%)  0/27 (0.00%)  3/115 (2.61%)  0/39 (0.00%)  0/45 (0.00%) 
Gastrointestinal disorders           
Abdominal Pain Upper * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Constipation * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Diarrhoea * 1  3/71 (4.23%)  1/27 (3.70%)  6/115 (5.22%)  0/39 (0.00%)  0/45 (0.00%) 
Diverticular Perforation * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Gastrointestinal Haemorrhage * 1  0/71 (0.00%)  1/27 (3.70%)  1/115 (0.87%)  1/39 (2.56%)  0/45 (0.00%) 
Large Intestinal Haemorrhage * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Mouth Ulceration * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Nausea * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Tooth Loss * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Vomiting * 1  4/71 (5.63%)  0/27 (0.00%)  3/115 (2.61%)  0/39 (0.00%)  0/45 (0.00%) 
General disorders           
Asthenia * 1  3/71 (4.23%)  0/27 (0.00%)  2/115 (1.74%)  2/39 (5.13%)  0/45 (0.00%) 
Condition Aggravated * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
General Physical Health Deterioration * 1  1/71 (1.41%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Malaise * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Multiple Organ Dysfunction Syndrome * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Pain * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Pyrexia * 1  4/71 (5.63%)  1/27 (3.70%)  7/115 (6.09%)  2/39 (5.13%)  1/45 (2.22%) 
Fatigue * 1  1/71 (1.41%)  0/27 (0.00%)  8/115 (6.96%)  0/39 (0.00%)  0/45 (0.00%) 
Hepatobiliary disorders           
Cholecystitis Acute * 1  0/71 (0.00%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Hyperbilirubinaemia * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Infections and infestations           
Arthritis Bacterial * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Aspergillus Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Biliary Sepsis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Biliary Tract Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cellulitis * 1  2/71 (2.82%)  0/27 (0.00%)  1/115 (0.87%)  1/39 (2.56%)  1/45 (2.22%) 
Clostridium Difficile Infection * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Device Related Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  1/39 (2.56%)  1/45 (2.22%) 
Diverticulitis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Escherichia Sepsis * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  1/45 (2.22%) 
Fungal Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  2/45 (4.44%) 
Klebsiella Sepsis * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Laryngitis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Lower Respiratory Tract Infection * 1  1/71 (1.41%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Lung Infection * 1  3/71 (4.23%)  1/27 (3.70%)  1/115 (0.87%)  3/39 (7.69%)  0/45 (0.00%) 
Necrotising Fasciitis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Neutropenic Sepsis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Penile Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Perirectal Abscess * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Pneumocystis Jirovecii Pneumonia * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Pneumonia * 1  10/71 (14.08%)  4/27 (14.81%)  10/115 (8.70%)  4/39 (10.26%)  3/45 (6.67%) 
Pneumonia Fungal * 1  2/71 (2.82%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Sepsis * 1  8/71 (11.27%)  1/27 (3.70%)  3/115 (2.61%)  3/39 (7.69%)  1/45 (2.22%) 
Septic Shock * 1  1/71 (1.41%)  0/27 (0.00%)  3/115 (2.61%)  1/39 (2.56%)  0/45 (0.00%) 
Sialoadenitis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Sinusitis * 1  2/71 (2.82%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Skin Infection * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Soft Tissue Infection * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Tonsillitis * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Upper Respiratory Tract Infection * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Urinary Tract Infection * 1  0/71 (0.00%)  0/27 (0.00%)  3/115 (2.61%)  1/39 (2.56%)  0/45 (0.00%) 
Urosepsis * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Vaginal Abscess * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Vulval Cellulitis * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Injury, poisoning and procedural complications           
Fall * 1  0/71 (0.00%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  1/45 (2.22%) 
Femur Fracture * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Subarachnoid Haemorrhage * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Subdural Haematoma * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  1/39 (2.56%)  0/45 (0.00%) 
Subdural Haemorrhage * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Investigations           
Blood Alkaline Phosphatase Increased * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
C-Reactive Protein Increased * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Electrocardiogram Change * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Enterococcus Test Positive * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Troponin T Increased * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Vitamin B12 Decreased * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Weight Decreased * 1  1/71 (1.41%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Metabolism and nutrition disorders           
Decreased Appetite * 1  1/71 (1.41%)  0/27 (0.00%)  6/115 (5.22%)  0/39 (0.00%)  0/45 (0.00%) 
Dehydration * 1  5/71 (7.04%)  0/27 (0.00%)  2/115 (1.74%)  1/39 (2.56%)  0/45 (0.00%) 
Failure To Thrive * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Fluid Overload * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  1/39 (2.56%)  0/45 (0.00%) 
Hypercreatininaemia * 1  0/71 (0.00%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Hyperglycaemia * 1  5/71 (7.04%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Hyperkalaemia * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Hyponatraemia * 1  3/71 (4.23%)  1/27 (3.70%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Hypophagia * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders           
Bone Pain * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Muscular Weakness * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal Cell Carcinoma * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cerebellar Tumour * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Squamous Cell Carcinoma * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Nervous system disorders           
Ataxia * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cerebral Haemorrhage * 1  1/71 (1.41%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  1/45 (2.22%) 
Cerebral Infarction * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Cerebrovascular Accident * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Dizziness * 1  1/71 (1.41%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Embolic Stroke * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Encephalopathy * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Haemorrhage Intracranial * 1  2/71 (2.82%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Haemorrhagic Cerebral Infarction * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Headache * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Ischaemic Stroke * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Loss Of Consciousness * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Nervous System Disorders * 1  8/71 (11.27%)  1/27 (3.70%)  15/115 (13.04%)  0/39 (0.00%)  1/45 (2.22%) 
Presyncope * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Syncope * 1  2/71 (2.82%)  1/27 (3.70%)  3/115 (2.61%)  0/39 (0.00%)  0/45 (0.00%) 
Psychiatric disorders           
Confusional State * 1  4/71 (5.63%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Hallucination * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Mental Status Changes * 1  1/71 (1.41%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Organic Brain Syndrome * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Renal and urinary disorders           
Acute Kidney Injury * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Oliguria * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Renal Failure * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Reproductive system and breast disorders           
Vaginal Haemorrhage * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Acute Respiratory Failure * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Cough * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Dyspnoea * 1  2/71 (2.82%)  1/27 (3.70%)  3/115 (2.61%)  1/39 (2.56%)  0/45 (0.00%) 
Epistaxis * 1  2/71 (2.82%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  2/45 (4.44%) 
Haemoptysis * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  1/45 (2.22%) 
Pleural Effusion * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  1/45 (2.22%) 
Pneumonia Aspiration * 1  2/71 (2.82%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Pulmonary Embolism * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Pulmonary Mass * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Respiratory Failure * 1  2/71 (2.82%)  0/27 (0.00%)  2/115 (1.74%)  0/39 (0.00%)  0/45 (0.00%) 
Social circumstances           
Social Stay Hospitalisation * 1  0/71 (0.00%)  1/27 (3.70%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Vascular disorders           
Aortic Aneurysm * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Haematoma * 1  1/71 (1.41%)  0/27 (0.00%)  0/115 (0.00%)  0/39 (0.00%)  0/45 (0.00%) 
Hypotension * 1  1/71 (1.41%)  0/27 (0.00%)  4/115 (3.48%)  0/39 (0.00%)  0/45 (0.00%) 
Peripheral Ischaemia * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
Thrombophlebitis * 1  0/71 (0.00%)  0/27 (0.00%)  0/115 (0.00%)  1/39 (2.56%)  0/45 (0.00%) 
Venous Thrombosis * 1  0/71 (0.00%)  0/27 (0.00%)  1/115 (0.87%)  0/39 (0.00%)  0/45 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   71/71 (100.00%)      27/27 (100.00%)      113/115 (98.26%)      37/39 (94.87%)      40/45 (88.89%)    
Blood and lymphatic system disorders           
Thrombocytopenia * 1  29/71 (40.85%)  29 7/27 (25.93%)  7 38/115 (33.04%)  38 18/39 (46.15%)  18 11/45 (24.44%)  11
Anaemia * 1  20/71 (28.17%)  20 7/27 (25.93%)  7 29/115 (25.22%)  29 17/39 (43.59%)  17 10/45 (22.22%)  10
Neutropenia * 1  6/71 (8.45%)  6 5/27 (18.52%)  5 17/115 (14.78%)  17 10/39 (25.64%)  10 9/45 (20.00%)  9
Leukopenia * 1  2/71 (2.82%)  2 3/27 (11.11%)  3 10/115 (8.70%)  10 5/39 (12.82%)  5 4/45 (8.89%)  4
Febrile Neutropenia * 1  9/71 (12.68%)  9 2/27 (7.41%)  2 7/115 (6.09%)  7 3/39 (7.69%)  3 2/45 (4.44%)  2
Leukocytosis * 1  6/71 (8.45%)  6 2/27 (7.41%)  2 6/115 (5.22%)  6 4/39 (10.26%)  4 0/45 (0.00%)  0
Lymphopenia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 2/39 (5.13%)  2 1/45 (2.22%)  1
Pancytopenia * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 2/39 (5.13%)  2 0/45 (0.00%)  0
Coagulopathy * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 2/115 (1.74%)  2 1/39 (2.56%)  1 0/45 (0.00%)  0
Lymphadenopathy * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 1/45 (2.22%)  1
Increased Tendency To Bruise * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Polycythaemia * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Splenomegaly * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Thrombocytosis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Cardiac disorders           
Tachycardia * 1  5/71 (7.04%)  5 1/27 (3.70%)  1 4/115 (3.48%)  4 0/39 (0.00%)  0 2/45 (4.44%)  2
Sinus Tachycardia * 1  4/71 (5.63%)  4 1/27 (3.70%)  1 2/115 (1.74%)  2 1/39 (2.56%)  1 0/45 (0.00%)  0
Atrial Fibrillation * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 2/39 (5.13%)  2 1/45 (2.22%)  1
Bradycardia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Acute Left Ventricular Failure * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Angina Pectoris * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Arrhythmia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Bundle Branch Block Right * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Cardiac Failure * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Cardiac Flutter * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Extrasystoles * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Palpitations * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Sinus Bradycardia * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Supraventricular Tachycardia * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Tachycardia Paroxysmal * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Ear and labyrinth disorders           
Deafness * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 1/45 (2.22%)  1
Ear Discomfort * 1  0/71 (0.00%)  0 2/27 (7.41%)  2 2/115 (1.74%)  2 0/39 (0.00%)  0 1/45 (2.22%)  1
Vertigo * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 3/115 (2.61%)  3 0/39 (0.00%)  0 1/45 (2.22%)  1
Ear Pain * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Tinnitus * 1  3/71 (4.23%)  3 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Ear Congestion * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Eustachian Tube Dysfunction * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Excessive Cerumen Production * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Hypoacusis * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Endocrine disorders           
Hypothyroidism * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 4/115 (3.48%)  4 1/39 (2.56%)  1 0/45 (0.00%)  0
Cushingoid * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Hyperthyroidism * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Eye disorders           
Vision Blurred * 1  8/71 (11.27%)  8 1/27 (3.70%)  1 9/115 (7.83%)  9 1/39 (2.56%)  1 0/45 (0.00%)  0
Visual Impairment * 1  4/71 (5.63%)  4 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 1/45 (2.22%)  1
Cataract * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 3/115 (2.61%)  3 0/39 (0.00%)  0 0/45 (0.00%)  0
Dry Eye * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Visual Acuity Reduced * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 1/45 (2.22%)  1
Conjunctival Haemorrhage * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 2/39 (5.13%)  2 0/45 (0.00%)  0
Eye Pain * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Lacrimation Increased * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Eye Haemorrhage * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Eyelid Oedema * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Ocular Hyperaemia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Periorbital Oedema * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Photopsia * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Retinal Haemorrhage * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Diplopia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Eye Inflammation * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Eye Swelling * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Eyelid Ptosis * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Vitreous Floaters * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Vitreous Haemorrhage * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Gastrointestinal disorders           
Nausea * 1  41/71 (57.75%)  41 16/27 (59.26%)  16 68/115 (59.13%)  68 13/39 (33.33%)  13 8/45 (17.78%)  8
Diarrhoea * 1  17/71 (23.94%)  17 13/27 (48.15%)  13 41/115 (35.65%)  41 8/39 (20.51%)  8 6/45 (13.33%)  6
Constipation * 1  20/71 (28.17%)  20 8/27 (29.63%)  8 25/115 (21.74%)  25 16/39 (41.03%)  16 15/45 (33.33%)  15
Vomiting * 1  19/71 (26.76%)  19 10/27 (37.04%)  10 30/115 (26.09%)  30 7/39 (17.95%)  7 6/45 (13.33%)  6
Stomatitis * 1  8/71 (11.27%)  8 0/27 (0.00%)  0 8/115 (6.96%)  8 3/39 (7.69%)  3 3/45 (6.67%)  3
Abdominal Pain * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 12/115 (10.43%)  12 2/39 (5.13%)  2 6/45 (13.33%)  6
Abdominal Pain Upper * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 6/115 (5.22%)  6 1/39 (2.56%)  1 1/45 (2.22%)  1
Dyspepsia * 1  3/71 (4.23%)  3 2/27 (7.41%)  2 3/115 (2.61%)  3 1/39 (2.56%)  1 1/45 (2.22%)  1
Gingival Bleeding * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 7/115 (6.09%)  7 1/39 (2.56%)  1 2/45 (4.44%)  2
Haemorrhoids * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 3/115 (2.61%)  3 2/39 (5.13%)  2 3/45 (6.67%)  3
Aphthous Ulcer * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 1/115 (0.87%)  1 2/39 (5.13%)  2 2/45 (4.44%)  2
Mouth Haemorrhage * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 4/115 (3.48%)  4 1/39 (2.56%)  1 0/45 (0.00%)  0
Abdominal Discomfort * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 1/115 (0.87%)  1 2/39 (5.13%)  2 2/45 (4.44%)  2
Gingival Pain * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 3/115 (2.61%)  3 2/39 (5.13%)  2 0/45 (0.00%)  0
Odynophagia * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 0/115 (0.00%)  0 2/39 (5.13%)  2 2/45 (4.44%)  2
Toothache * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 3/115 (2.61%)  3 0/39 (0.00%)  0 1/45 (2.22%)  1
Dry Mouth * 1  2/71 (2.82%)  2 1/27 (3.70%)  1 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Gastrooesophageal Reflux Disease * 1  3/71 (4.23%)  3 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Dysphagia * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Flatulence * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 3/115 (2.61%)  3 1/39 (2.56%)  1 0/45 (0.00%)  0
Melaena * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 2/45 (4.44%)  2
Oral Pain * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 2/39 (5.13%)  2 0/45 (0.00%)  0
Abdominal Pain Lower * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Anal Fissure * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Angina Bullosa Haemorrhagica * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 2/39 (5.13%)  2 0/45 (0.00%)  0
Enterocolitis * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Eructation * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Gastritis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Gastrointestinal Haemorrhage * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Mouth Ulceration * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Oral Disorder * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Oral Mucosa Haematoma * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Oral Mucosal Blistering * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Abdominal Tenderness * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Anal Incontinence * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Breath Odour * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Diverticulum * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Faeces Soft * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Gastrointestinal Pain * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Gingival Hypertrophy * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Glossitis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Ileus * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Inguinal Hernia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Lip Blister * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Lip Dry * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Lip Oedema * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Lip Pain * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Lip Swelling * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Lip Ulceration * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Mouth Swelling * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Oesophagitis * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Oral Contusion * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Oral Dysaesthesia * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Palatal Disorder * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Perianal Erythema * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Proctalgia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Rectal Fissure * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Rectal Haemorrhage * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Retching * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Salivary Hypersecretion * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Tongue Haematoma * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Tongue Ulceration * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Tooth Loss * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Trichoglossia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
General disorders           
Fatigue * 1  33/71 (46.48%)  33 13/27 (48.15%)  13 50/115 (43.48%)  50 15/39 (38.46%)  15 13/45 (28.89%)  13
Pyrexia * 1  8/71 (11.27%)  8 5/27 (18.52%)  5 28/115 (24.35%)  28 13/39 (33.33%)  13 13/45 (28.89%)  13
Oedema Peripheral * 1  17/71 (23.94%)  17 5/27 (18.52%)  5 21/115 (18.26%)  21 10/39 (25.64%)  10 5/45 (11.11%)  5
Asthenia * 1  17/71 (23.94%)  17 6/27 (22.22%)  6 22/115 (19.13%)  22 5/39 (12.82%)  5 5/45 (11.11%)  5
Malaise * 1  2/71 (2.82%)  2 1/27 (3.70%)  1 8/115 (6.96%)  8 3/39 (7.69%)  3 1/45 (2.22%)  1
Oedema * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 5/115 (4.35%)  5 4/39 (10.26%)  4 2/45 (4.44%)  2
Chills * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 5/115 (4.35%)  5 3/39 (7.69%)  3 1/45 (2.22%)  1
Mucosal Inflammation * 1  3/71 (4.23%)  3 0/27 (0.00%)  0 1/115 (0.87%)  1 4/39 (10.26%)  4 3/45 (6.67%)  3
Pain * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 7/115 (6.09%)  7 1/39 (2.56%)  1 1/45 (2.22%)  1
Gait Disturbance * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
General Physical Health Deterioration * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Injection Site Bruising * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 1/45 (2.22%)  1
Non-Cardiac Chest Pain * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Ulcer * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Catheter Site Haemorrhage * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Face Oedema * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Generalised Oedema * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Secretion Discharge * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Catheter Site Haematoma * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Chest Pain * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Drug Intolerance * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Extravasation * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Feeling Cold * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Granuloma * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Hernia * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Impaired Healing * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Infusion Site Haemorrhage * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Injection Site Discolouration * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Injection Site Pain * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Mucosal Dryness * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Nodule * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Peripheral Swelling * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Swelling * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Decreased Appetite * 1  41/71 (57.75%)  41 12/27 (44.44%)  12 61/115 (53.04%)  61 9/39 (23.08%)  9 7/45 (15.56%)  7
Hepatobiliary disorders           
Hyperbilirubinaemia * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 5/115 (4.35%)  5 1/39 (2.56%)  1 1/45 (2.22%)  1
Cholelithiasis * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Hepatomegaly * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Jaundice * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Ocular Icterus * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Immune system disorders           
Hypersensitivity * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Infections and infestations           
Urinary Tract Infection * 1  6/71 (8.45%)  6 2/27 (7.41%)  2 9/115 (7.83%)  9 5/39 (12.82%)  5 2/45 (4.44%)  2
Oral Herpes * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 3/115 (2.61%)  3 4/39 (10.26%)  4 4/45 (8.89%)  4
Nasopharyngitis * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 5/115 (4.35%)  5 1/39 (2.56%)  1 3/45 (6.67%)  3
Oral Candidiasis * 1  4/71 (5.63%)  4 0/27 (0.00%)  0 4/115 (3.48%)  4 1/39 (2.56%)  1 1/45 (2.22%)  1
Pneumonia * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 4/115 (3.48%)  4 3/39 (7.69%)  3 1/45 (2.22%)  1
Cellulitis * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 2/115 (1.74%)  2 1/39 (2.56%)  1 1/45 (2.22%)  1
Lung Infection * 1  2/71 (2.82%)  2 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Sinusitis * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 2/115 (1.74%)  2 2/39 (5.13%)  2 0/45 (0.00%)  0
Upper Respiratory Tract Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 1/39 (2.56%)  1 1/45 (2.22%)  1
Device Related Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 2/115 (1.74%)  2 1/39 (2.56%)  1 0/45 (0.00%)  0
Periodontitis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 2/45 (4.44%)  2
Pneumonia Fungal * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 3/45 (6.67%)  3
Sepsis * 1  1/71 (1.41%)  1 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Candida Infection * 1  3/71 (4.23%)  3 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Folliculitis * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Oesophageal Candidiasis * 1  0/71 (0.00%)  0 2/27 (7.41%)  2 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Skin Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 1/39 (2.56%)  1 0/45 (0.00%)  0
Staphylococcal Infection * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 2/45 (4.44%)  2
Clostridium Difficile Colitis * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Clostridium Difficile Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Conjunctivitis * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Ear Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Fungal Infection * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 2/115 (1.74%)  2 0/39 (0.00%)  0 0/45 (0.00%)  0
Herpes Dermatitis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Infection * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 1/39 (2.56%)  1 1/45 (2.22%)  1
Lip Infection * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Nasal Herpes * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 0/45 (0.00%)  0
Pharyngitis * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 0/115 (0.00%)  0 2/39 (5.13%)  2 0/45 (0.00%)  0
Pseudomonas Infection * 1  0/71 (0.00%)  0 0/27 (0.00%)  0 1/115 (0.87%)  1 0/39 (0.00%)  0 1/45 (2.22%)  1
Rash Pustular * 1  0/71 (0.00%)  0 1/27 (3.70%)  1 0/115 (0.00%)  0 1/39 (2.56%)  1 0/45 (0.00%)  0
Rhinovirus Infection * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 1/45 (2.22%)  1
Soft Tissue Infection * 1  2/71 (2.82%)  2 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Abscess Limb * 1  1/71 (1.41%)  1 0/27 (0.00%)  0 0/115 (0.00%)  0 0/39 (0.00%)  0 0/45 (0.00%)  0
Acute Sinusitis * 1