Trial Outcomes & Findings for Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (NCT NCT00333840)
NCT ID: NCT00333840
Last Updated: 2013-10-14
Results Overview
Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1106 participants
Primary outcome timeframe
12,24,36,48,60,72,84,96,108,120,132 and 144 months
Results posted on
2013-10-14
Participant Flow
Participant milestones
| Measure |
Imatinib (STI571)
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
Imatinib to IFN-a + Ara-C
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month.
|
IFN-a + Ara-C to Imatinib
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571) 400 mg orally once daily in the morning.
|
|---|---|---|---|---|
|
First-line Treatment Period
STARTED
|
553
|
553
|
0
|
0
|
|
First-line Treatment Period
Safety Population; Received Study Drug
|
551
|
533
|
0
|
0
|
|
First-line Treatment Period
COMPLETED
|
267
|
7
|
0
|
0
|
|
First-line Treatment Period
NOT COMPLETED
|
286
|
546
|
0
|
0
|
|
Second-line Treatment Period
STARTED
|
0
|
0
|
14
|
363
|
|
Second-line Treatment Period
COMPLETED
|
0
|
0
|
0
|
175
|
|
Second-line Treatment Period
NOT COMPLETED
|
0
|
0
|
14
|
188
|
Reasons for withdrawal
| Measure |
Imatinib (STI571)
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
Imatinib to IFN-a + Ara-C
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month.
|
IFN-a + Ara-C to Imatinib
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571) 400 mg orally once daily in the morning.
|
|---|---|---|---|---|
|
First-line Treatment Period
Adverse Event
|
38
|
37
|
0
|
0
|
|
First-line Treatment Period
Abnormal laboratory values
|
3
|
1
|
0
|
0
|
|
First-line Treatment Period
Abnormal procedure
|
2
|
0
|
0
|
0
|
|
First-line Treatment Period
Unsatisfactory therapeutic effect
|
88
|
29
|
0
|
0
|
|
First-line Treatment Period
No longer required study drug
|
21
|
8
|
0
|
0
|
|
First-line Treatment Period
Protocol Violation
|
17
|
17
|
0
|
0
|
|
First-line Treatment Period
Subject withdrew consent
|
57
|
77
|
0
|
0
|
|
First-line Treatment Period
Lost to Follow-up
|
15
|
6
|
0
|
0
|
|
First-line Treatment Period
Administrative problems
|
12
|
6
|
0
|
0
|
|
First-line Treatment Period
Death
|
19
|
2
|
0
|
0
|
|
First-line Treatment Period
Crossed over to other treatment arm
|
14
|
363
|
0
|
0
|
|
Second-line Treatment Period
Adverse Event
|
0
|
0
|
3
|
34
|
|
Second-line Treatment Period
Abnormal Laboratory Values
|
0
|
0
|
0
|
3
|
|
Second-line Treatment Period
Abnormal procedure
|
0
|
0
|
0
|
1
|
|
Second-line Treatment Period
Unsatisfactory therapeutic effect
|
0
|
0
|
9
|
70
|
|
Second-line Treatment Period
No longer required study drug
|
0
|
0
|
1
|
14
|
|
Second-line Treatment Period
Protocol Violation
|
0
|
0
|
1
|
10
|
|
Second-line Treatment Period
Subject withdrew consent
|
0
|
0
|
0
|
34
|
|
Second-line Treatment Period
Lost to Follow-up
|
0
|
0
|
0
|
6
|
|
Second-line Treatment Period
Administrative problems
|
0
|
0
|
0
|
7
|
|
Second-line Treatment Period
Death
|
0
|
0
|
0
|
9
|
Baseline Characteristics
Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
Baseline characteristics by cohort
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (CSI151). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
Total
n=1106 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
50.0 years
n=5 Participants
|
51.0 years
n=7 Participants
|
51.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
211 Participants
n=5 Participants
|
243 Participants
n=7 Participants
|
454 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
342 Participants
n=5 Participants
|
310 Participants
n=7 Participants
|
652 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 monthsPopulation: Intent-to-treat population included all randomized participants. n = number of participants at risk at the beginning of the specific time interval
Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
12 months (n = 553, 553)
|
98.9 Percentage of participants
Interval 98.0 to 100.0
|
97.7 Percentage of participants
Interval 96.0 to 99.0
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
24 months (n = 542, 512)
|
96.0 Percentage of participants
|
93.6 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
36 months (n = 518, 471)
|
92.4 Percentage of participants
|
89.8 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
48 months (n = 492, 441)
|
90.4 Percentage of participants
|
87.7 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
60 months (n = 475, 411)
|
89.4 Percentage of participants
|
85.4 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
72 months (n = 461, 388)
|
88.2 Percentage of participants
|
83.8 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
84 months (n = 446, 373)
|
86.6 Percentage of participants
|
83.1 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
96 months (n = 430, 358)
|
85.4 Percentage of participants
|
81.4 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
108 months (n = 391, 315)
|
84.3 Percentage of participants
|
79.9 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
120 months (n = 368, 299)
|
83.3 Percentage of participants
|
78.8 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
132 months (n = 356, 288)
|
82.8 Percentage of participants
|
77.7 Percentage of participants
|
|
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
144 months (n = 250, 199)
|
81.3 Percentage of participants
|
75.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 monthsPopulation: Intent-to-treat population included all randomized participants. n = number of participants at risk at the beginning of the specific time interval
Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment: * progression to Accelerated Phase (AP) or Blast Crisis (BC) * loss of Complete Hematological Response (CHR) * loss of Major Cytogenetic Response (MCyR) confirmed * loss of Major Cytogenetic Response (MCyR) unconfirmed * increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC) * death (due to any cause when reported as primary reason for discontinuation of treatment). Kaplan Meier estimates of the percentage of participants with Event Free Survival at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
12 months (n = 553, 553)
|
96.6 Percentage of participants
|
79.4 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
24 months (n = 505, 332)
|
89.6 Percentage of participants
|
70.0 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
36 months (n = 448, 263)
|
85.3 Percentage of participants
|
67.0 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
48 months (n = 415, 241)
|
83.9 Percentage of participants
|
63.7 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
60 months (n = 395, 223)
|
83.2 Percentage of participants
|
61.9 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
72 months (n = 376, 207)
|
83.0 Percentage of participants
|
60.1 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
84 months (n = 352, 181)
|
82.0 Percentage of participants
|
59.0 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
96 months (n = 334, 166)
|
81.0 Percentage of participants
|
58.3 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
108 months (n = 301, 141)
|
79.9 Percentage of participants
|
56.6 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
120 months (n = 269, 130)
|
79.6 Percentage of participants
|
56.6 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
132 months (n = 257, 124)
|
79.6 Percentage of participants
|
56.6 Percentage of participants
|
|
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
144 months (n = 143, 76)
|
79.6 Percentage of participants
|
51.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 144 monthsPopulation: Intent-to-treat population included all randomized participants.
Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment: * progression to Accelerated Phase (AP) or Blast Crisis (BC) * loss of Complete Hematological Response (CHR) * loss of Major Cytogenic Response (MCyR) confirmed * loss of Major Cytogenic Response (MCyR) unconfirmed * increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC) * death (due to any cause when reported as primary reason for discontinuation of treatment). The percentage of participants with Event Free Survival events in each category was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Participants with events
|
17.9 Percentage of participants
|
32.2 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Progression to AP or BC
|
6.9 Percentage of participants
|
12.8 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Loss of CHR
|
2.7 Percentage of participants
|
7.6 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Loss of MCyR (confirmed)
|
4.2 Percentage of participants
|
5.4 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Loss of MCyR (unconfirmed)
|
0.9 Percentage of participants
|
1.1 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Increase of WBC
|
0.2 Percentage of participants
|
3.4 Percentage of participants
|
|
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
Death
|
3.1 Percentage of participants
|
1.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 monthsPopulation: Intent-to-treat population included all randomized participants. n = number of participants at risk at the beginning of the specific time interval
Time to progression to AP/BC is defined as the time between randomization and either of the following events on treatment: death (due to CML when reported as primary reason for discontinuation of treatment) or progression to Accelerated Phase or Blast Crisis and is censored at last examination date for patients without event. No data after discontinuation of study treatment was included. The Kaplan Meier estimates of the percentage of participants with survival without progression to AP/BC at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
12 months (n = 553, 553)
|
98.5 Percentage of participants
|
92.9 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
24 months (n = 513, 388)
|
95.7 Percentage of participants
|
90.0 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
36 months (n = 461, 337)
|
94.0 Percentage of participants
|
87.9 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
48 months (n = 431, 311)
|
93.1 Percentage of participants
|
84.7 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
60 months (n = 409, 289 )
|
92.7 Percentage of participants
|
83.5 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
72 months (n = 384, 265)
|
92.7 Percentage of participants
|
83.1 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
84 months (n = 358, 236)
|
92.7 Percentage of participants
|
82.4 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
96 months (n = 338, 220)
|
92.4 Percentage of participants
|
82.4 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
108 months (n = 305, 189)
|
92.1 Percentage of participants
|
82.4 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
120 months (n = 272, 175)
|
92.1 Percentage of participants
|
82.4 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
132 months (n = 259, 165)
|
92.1 Percentage of participants
|
82.4 Percentage of participants
|
|
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
144 months (n = 145, 94)
|
92.1 Percentage of participants
|
82.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 144 monthsPopulation: Intent-to-treat participants included all randomized participants.
Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Philadelphia chromosome positive (Ph+) metaphases) and amount of blasts and promyelocytes in bone marrow to establish cytogenetic response. Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= \> 0 and ≤ 35 % of Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
Major Cytogenic Response
|
89.0 Percentage of participants
|
23.3 Percentage of participants
|
|
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
Complete Cytogenic Response
|
82.8 Percentage of participants
|
11.6 Percentage of participants
|
|
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
Partial Cytogenic Response
|
6.1 Percentage of participants
|
11.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 144 monthsPopulation: Intent-to-treat participants included all randomized participants.
Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Ph chromosome (Ph+) containing metaphases) and the amount of blasts and promyelocytes in bone marrow to establish cytogenetic response. Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= \> 0 and ≤ 35 % Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.
Outcome measures
| Measure |
Imatinib (STI571)
n=14 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=363 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
Major Cytogenic Response
|
14.3 Percentage of participants
|
86.0 Percentage of participants
|
|
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
Complete Cytogenic Response
|
7.1 Percentage of participants
|
81.0 Percentage of participants
|
|
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
Partial Cytogenic Response
|
7.1 Percentage of participants
|
5.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 144 monthsPopulation: Safety Population included all randomized participants who received study drug.
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant
Outcome measures
| Measure |
Imatinib (STI571)
n=551 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=533 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
|
226 Participants
|
163 Participants
|
SECONDARY outcome
Timeframe: 144 monthsPopulation: Safety Population included all randomized participants who received study drug.
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant
Outcome measures
| Measure |
Imatinib (STI571)
n=14 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=363 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
|
2 Participants
|
160 Participants
|
SECONDARY outcome
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 monthsPopulation: Intent-to-treat population included all randomized participants.
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale.
Outcome measures
| Measure |
Imatinib (STI571)
n=553 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=553 Participants
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
144 months (n= 1, 0)
|
100.0 Percentage of participants
|
NA Percentage of participants
Because this table refers to first-line therapy only and not cross-over, no participants were available for testing from Month 108 to Month 144.
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
12 months (n= 305, 83)
|
50.2 Percentage of participants
|
9.6 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
24 months (n= 102, 12)
|
69.6 Percentage of participants
|
25.0 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
36 months (n= 68, 7)
|
76.5 Percentage of participants
|
28.6 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
48 months (n= 305, 12)
|
77.0 Percentage of participants
|
58.3 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
60 months (n= 316, 10)
|
88.0 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
72 months (n= 292, 9)
|
88.0 Percentage of participants
|
88.9 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
84 months (n= 247, 8)
|
91.9 Percentage of participants
|
87.5 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
96 months (n= 228, 4)
|
92.5 Percentage of participants
|
100.0 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
108 months (n= 233, 0)
|
93.6 Percentage of participants
|
NA Percentage of participants
Because this table refers to first-line therapy only and not cross-over, no participants were available for testing from Month 108 to Month 144.
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
120 months (n= 204, 0)
|
93.1 Percentage of participants
|
NA Percentage of participants
Because this table refers to first-line therapy only and not cross-over, no participants were available for testing from Month 108 to Month 144.
|
|
Percentage of Participants With Major Molecular Response (First-line Treatment)
132 months (n= 168, 0)
|
92.3 Percentage of participants
|
NA Percentage of participants
Because this table refers to first-line therapy only and not cross-over, no participants were available for testing from Month 108 to Month 144.
|
SECONDARY outcome
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 monthsPopulation: Intent-to-treat population included all randomized participants. No participants in the imatinib to IFN-a + Ara-C arm were available for testing.
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale.
Outcome measures
| Measure |
Imatinib (STI571)
n=363 Participants
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C). Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
|---|---|---|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
12 months (n = 86)
|
51.2 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
24 months (n = 62)
|
69.4 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
36 months (n = 130)
|
78.5 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
48 months (n = 216)
|
81.9 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
60 months (n = 174)
|
86.2 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
72 months (n = 146)
|
91.1 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
84 months (n = 139)
|
86.3 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
96 months (n = 138)
|
87.0 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
108 months (n = 120)
|
90.0 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
120 months (n = 84)
|
85.7 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
132 months (n = 31)
|
90.3 Percentage of participants
|
—
|
|
Percentage of Participants With Major Molecular Response (Second-line Treatment)
144 months
|
NA Percentage of participants
No participants were available for testing at this specific time point, or patients had no PCR assessment done.
|
—
|
Adverse Events
Imatinib (STI571)
Serious events: 226 serious events
Other events: 541 other events
Deaths: 0 deaths
IFN-a + Ara-C
Serious events: 163 serious events
Other events: 531 other events
Deaths: 0 deaths
Imatinib to IFN-a + Ara-C
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
IFN-a + Ara-C to Imatinib
Serious events: 160 serious events
Other events: 347 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Imatinib (STI571)
n=551 participants at risk
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C) in the second-line treatment period. Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=533 participants at risk
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
Imatinib to IFN-a + Ara-C
n=14 participants at risk
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month.
|
IFN-a + Ara-C to Imatinib
n=363 participants at risk
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571) 400 mg orally once daily in the morning.
|
|---|---|---|---|---|
|
Infections and infestations
Rectal abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Respiratory tract infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Respiratory tract infection viral
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Rhinitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Salmonellosis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Infections and infestations
Salpingitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Scrotal abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Scrotal gangrene
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Sepsis
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Infections and infestations
Septic shock
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Sinusitis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Staphylococcal infection
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Streptococcal infection
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Subcutaneous abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Systemic candida
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Tonsillitis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Tooth abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Tracheobronchitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Tuberculoma of central nervous system
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Acquired Von Willebrand's disease
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Anaemia
|
1.1%
6/551
|
1.9%
10/533
|
0.00%
0/14
|
1.4%
5/363
|
|
Blood and lymphatic system disorders
Autoimmune thrombocytopenia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Blood and lymphatic system disorders
Haematotoxicity
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/551
|
0.56%
3/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Lymph node pain
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
1.1%
4/363
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.18%
1/551
|
1.9%
10/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Acute myocardial infarction
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Angina pectoris
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Angina unstable
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Aortic valve disease
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Aortic valve stenosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Arrhythmia
|
0.73%
4/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Atrial fibrillation
|
0.91%
5/551
|
0.56%
3/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Cardiac disorders
Bradycardia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Cardiac arrest
|
0.91%
5/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Cardiac failure
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Cardiac failure congestive
|
0.73%
4/551
|
0.75%
4/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Cardiac tamponade
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Cardiomegaly
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Cardiomyopathy
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Cardiovascular disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Conduction disorder
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Coronary artery disease
|
1.3%
7/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Heart valve incompetence
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Cardiac disorders
Left ventricular failure
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Mitral valve stenosis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Myocardial infarction
|
1.3%
7/551
|
0.94%
5/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Cardiac disorders
Nodal arrhythmia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Palpitations
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Pericardial effusion
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Pericarditis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Sick sinus syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Sinus arrhythmia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Torsade de pointes
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Ventricular fibrillation
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Cardiac disorders
Ventricular tachycardia
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Congenital, familial and genetic disorders
Gene mutation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Congenital, familial and genetic disorders
Sensory neuropathy hereditary
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Endocrine disorders
Goitre
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Endocrine disorders
Hyperparathyroidism
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Endocrine disorders
Hypopituitarism
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Blindness
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Blindness unilateral
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Conjunctival haemorrhage
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Diabetic retinopathy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Diplopia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Eyelid oedema
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Glaucoma
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Open angle glaucoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Papilloedema
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Retinal detachment
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Retinal haemorrhage
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Retinal vein thrombosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Vision blurred
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Eye disorders
Vitreous haemorrhage
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Abdominal distension
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Abdominal mass
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
12/551
|
0.19%
1/533
|
0.00%
0/14
|
1.4%
5/363
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.73%
4/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.3%
7/551
|
0.56%
3/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Abdominal tenderness
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Acute abdomen
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Anal fistula
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Barrett's oesophagus
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Colitis
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Constipation
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Crohn's disease
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
9/551
|
0.38%
2/533
|
0.00%
0/14
|
1.4%
5/363
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Duodenitis
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Dysphagia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Faecal vomiting
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Faecaloma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Flatulence
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Gastritis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Gastrointestinal ulcer
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Gingival pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Inflammatory bowel disease
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Melaena
|
0.36%
2/551
|
0.38%
2/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Nausea
|
1.3%
7/551
|
1.5%
8/533
|
0.00%
0/14
|
1.1%
4/363
|
|
Gastrointestinal disorders
Odynophagia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Oedematous pancreatitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Painful defaecation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Pancreatic pseudocyst
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Pancreatitis
|
0.54%
3/551
|
0.38%
2/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Proctalgia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Proctitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Sigmoiditis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Gastrointestinal disorders
Subileus
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Tongue cyst
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
11/551
|
1.3%
7/533
|
0.00%
0/14
|
0.55%
2/363
|
|
General disorders
Abasia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Adverse drug reaction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Asthenia
|
0.36%
2/551
|
0.75%
4/533
|
0.00%
0/14
|
0.83%
3/363
|
|
General disorders
Cardiac death
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Chest discomfort
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Chest pain
|
2.5%
14/551
|
0.75%
4/533
|
0.00%
0/14
|
1.9%
7/363
|
|
General disorders
Chills
|
1.3%
7/551
|
0.75%
4/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Condition aggravated
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Crepitations
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Device malfunction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Drug ineffective
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
General disorders
Drug interaction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Drug intolerance
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Fatigue
|
0.54%
3/551
|
1.3%
7/533
|
7.1%
1/14
|
0.83%
3/363
|
|
General disorders
Gait disturbance
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
General physical health deterioration
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.83%
3/363
|
|
General disorders
Generalised oedema
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Granuloma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Hernia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Hyperplasia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Hyperthermia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Impaired healing
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Influenza like illness
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Malaise
|
0.73%
4/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Mucosal atrophy
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Multi-organ failure
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Necrosis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Oedema peripheral
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Pain
|
0.73%
4/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Performance status decreased
|
0.18%
1/551
|
0.38%
2/533
|
0.00%
0/14
|
0.28%
1/363
|
|
General disorders
Pyrexia
|
3.4%
19/551
|
3.8%
20/533
|
7.1%
1/14
|
3.3%
12/363
|
|
General disorders
Soft tissue inflammation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Spinal pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Sudden cardiac death
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Hepatobiliary disorders
Bile duct stone
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Biliary tract disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Cholangitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Cholecystitis
|
1.1%
6/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.73%
4/551
|
0.38%
2/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Gallbladder perforation
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Hepatobiliary disorders
Granulomatous liver disease
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Hepatobiliary disorders
Hepatic failure
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatic necrosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatitis acute
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Jaundice
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Immune system disorders
Anaphylactic shock
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Immune system disorders
Drug hypersensitivity
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Immune system disorders
Transplant rejection
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Abscess
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Amoebiasis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Anal abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Anorectal infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Appendicitis
|
0.73%
4/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Bacteraemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Bacterial infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Bone tuberculosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Bronchitis
|
0.36%
2/551
|
0.38%
2/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Bronchitis viral
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Cellulitis
|
1.1%
6/551
|
0.56%
3/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Infections and infestations
Clostridium difficile colitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Diverticulitis
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Ear infection
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Epstein-Barr virus infection
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Folliculitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Gangrene
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Gastritis viral
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Gastroenteritis
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Gastroenteritis rotavirus
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Gastroenteritis viral
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Gastrointestinal infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Haemophilus infection
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Hepatitis B
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Incision site infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Infection
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Infections and infestations
Influenza
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Lobar pneumonia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Localised infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Lower respiratory tract infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Infections and infestations
Lung infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Malaria
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Meningitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Meningitis pneumococcal
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Meningoencephalitis herpetic
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Muscle abscess
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Mycoplasma infection
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Neutropenic sepsis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Orchitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Parotitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Pelvic abscess
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Peridiverticular abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Perirectal abscess
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Pharyngitis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Pneumococcal sepsis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Pneumonia
|
2.2%
12/551
|
1.3%
7/533
|
0.00%
0/14
|
3.9%
14/363
|
|
Infections and infestations
Pneumonia streptococcal
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Post procedural infection
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Prostate infection
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Pseudomembranous colitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Upper respiratory tract infection
|
0.73%
4/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Urinary tract infection
|
0.73%
4/551
|
0.75%
4/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Urosepsis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Viral infection
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Infections and infestations
Vulvitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Wound infection
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Infections and infestations
Wound infection staphylococcal
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Concussion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Contusion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Exposure via father
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Fall
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Graft dysfunction
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Head injury
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Overdose
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Skull fractured base
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/551
|
0.56%
3/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Urethral stricture postoperative
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Vascular graft occlusion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Vascular injury
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Alanine aminotransferase increased
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Amylase increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Aspartate aminotransferase abnormal
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Aspartate aminotransferase increased
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blast cell count increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blast cells present
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood alkaline phosphatase increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood creatine increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood creatine phosphokinase increased
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood creatinine increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood culture positive
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Blood parathyroid hormone increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Blood pressure increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Body temperature increased
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Creatinine renal clearance decreased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Echocardiogram abnormal
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Haemoglobin decreased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Investigations
Heart rate increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Hepatic enzyme increased
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Lipase increased
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Liver function test abnormal
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Investigations
Multiple gated acquisition scan abnormal
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Myelocyte present
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Platelet count increased
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Prostatic specific antigen increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Investigations
Troponin increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Investigations
Weight decreased
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Investigations
White blood cell count increased
|
0.00%
0/551
|
0.75%
4/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/551
|
0.56%
3/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Dehydration
|
0.91%
5/551
|
0.94%
5/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Food intolerance
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.36%
2/551
|
0.38%
2/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.73%
4/551
|
2.1%
11/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.73%
4/551
|
1.1%
6/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Bone disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.36%
2/551
|
1.1%
6/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Musculoskeletal and connective tissue disorders
Compartment syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Inclusion body myositis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.73%
4/551
|
0.19%
1/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Mixed connective tissue disease
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Muscle atrophy
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
1.1%
4/363
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.18%
1/551
|
1.9%
10/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Neck mass
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.91%
5/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Osteolysis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Osteoporotic fracture
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.73%
4/551
|
0.94%
5/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acral lentiginous melanoma stage unspecified
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.1%
6/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign anorectal neoplasm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast cell crisis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast crisis in myelogenous leukaemia
|
0.73%
4/551
|
0.94%
5/533
|
0.00%
0/14
|
3.3%
12/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast neoplasm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchioloalveolar carcinoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoma in situ
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chloroma
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesteatoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia transformation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Erythroleukaemia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hypergammaglobulinaemia benign monoclonal
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip and/or oral cavity cancer recurrent
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to adrenals
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to large intestine
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic renal cell carcinoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
0.73%
4/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelofibrosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.73%
4/551
|
0.38%
2/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm of appendix
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nephroblastoma
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine tumour
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Paraneoplastic syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
2.0%
11/551
|
0.19%
1/533
|
0.00%
0/14
|
2.5%
9/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer metastatic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Signet-ring cell carcinoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
1.1%
6/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the cervix
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid adenoma
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage unspecified
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Amyotrophic lateral sclerosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Aphasia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Areflexia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Ataxia
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Balance disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Brain mass
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Carotid artery aneurysm
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Carotid artery occlusion
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Carotid artery stenosis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Cerebellar syndrome
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Cerebral artery occlusion
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Cerebral infarction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Cerebrovascular accident
|
0.18%
1/551
|
0.38%
2/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Nervous system disorders
Cervicobrachial syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Coma
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Complex regional pain syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Complicated migraine
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Convulsion
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Dementia
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Dementia Alzheimer's type
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Demyelination
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Diabetic neuropathy
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Dizziness
|
1.3%
7/551
|
0.94%
5/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Headache
|
0.54%
3/551
|
0.56%
3/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Nervous system disorders
Hemiparesis
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Intercostal neuralgia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Intracranial pressure increased
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Ischaemic stroke
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Loss of consciousness
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Migraine
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Monoparesis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Multiple sclerosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Neurological symptom
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Neurotoxicity
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Paraplegia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Piriformis syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Polyneuropathy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Presyncope
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Radiculopathy
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Sciatica
|
0.36%
2/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Simple partial seizures
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Somnolence
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Syncope
|
1.5%
8/551
|
0.75%
4/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Nervous system disorders
Temporal lobe epilepsy
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
Transient global amnesia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Nervous system disorders
Transient ischaemic attack
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Nervous system disorders
Tremor
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Psychiatric disorders
Aggression
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Agitation
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Anxiety
|
0.18%
1/551
|
0.56%
3/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/551
|
0.56%
3/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Delirium
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Depression
|
0.36%
2/551
|
2.8%
15/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Psychiatric disorders
Depression suicidal
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Homicidal ideation
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Mania
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Psychiatric disorders
Paranoia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/551
|
0.94%
5/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Calculus urethral
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Haematuria
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.1%
6/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Oliguria
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Renal colic
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Renal failure
|
0.91%
5/551
|
0.38%
2/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Renal and urinary disorders
Renal failure acute
|
0.91%
5/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Renal and urinary disorders
Renal failure chronic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Urethral stenosis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Breast mass
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Epididymitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Reproductive system and breast disorders
Penis disorder
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Reproductive system and breast disorders
Prostatic dysplasia
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Testicular swelling
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Reproductive system and breast disorders
Vaginal cyst
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Reproductive system and breast disorders
Varicose veins pelvic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Respiratory, thoracic and mediastinal disorders
Chronic respiratory failure
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
11/551
|
0.75%
4/533
|
0.00%
0/14
|
1.7%
6/363
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.36%
2/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.18%
1/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal stenosis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Pickwickian syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.91%
5/551
|
0.38%
2/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.54%
3/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.54%
3/551
|
0.19%
1/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.73%
4/551
|
0.38%
2/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Skin and subcutaneous tissue disorders
Cutaneous vasculitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Polymorphic light eruption
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.55%
2/363
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Social circumstances
Cardiac assistance device user
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Social circumstances
Disability
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Social circumstances
Miscarriage of partner
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Surgical and medical procedures
Abortion induced
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Surgical and medical procedures
Abscess drainage
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Surgical and medical procedures
Bone marrow transplant
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Surgical and medical procedures
Coronary arterial stent insertion
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Surgical and medical procedures
Stem cell transplant
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Vascular disorders
Aneurysm
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Aortic stenosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Arterial occlusive disease
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Arteriosclerosis
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Circulatory collapse
|
0.36%
2/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Deep vein thrombosis
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Vascular disorders
Femoral artery occlusion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Haematoma
|
0.18%
1/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Haemorrhage
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Hypertension
|
0.91%
5/551
|
0.19%
1/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Hypotension
|
0.18%
1/551
|
0.75%
4/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Iliac artery occlusion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Iliac artery stenosis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Infarction
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Ischaemia
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/551
|
0.00%
0/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/551
|
0.38%
2/533
|
0.00%
0/14
|
0.28%
1/363
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Peripheral vascular disorder
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Phlebitis
|
0.00%
0/551
|
0.19%
1/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Varicophlebitis
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
|
Vascular disorders
Vascular occlusion
|
0.18%
1/551
|
0.00%
0/533
|
0.00%
0/14
|
0.00%
0/363
|
Other adverse events
| Measure |
Imatinib (STI571)
n=551 participants at risk
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) and cytarabine (ARA-C) in the second-line treatment period. Maximum study duration was 11.5 years.
|
IFN-a + Ara-C
n=533 participants at risk
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
|
Imatinib to IFN-a + Ara-C
n=14 participants at risk
In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month.
|
IFN-a + Ara-C to Imatinib
n=363 participants at risk
In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571) 400 mg orally once daily in the morning.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
22.9%
126/551
|
27.2%
145/533
|
14.3%
2/14
|
18.7%
68/363
|
|
General disorders
Asthenia
|
7.8%
43/551
|
16.3%
87/533
|
14.3%
2/14
|
8.3%
30/363
|
|
General disorders
Chest pain
|
8.3%
46/551
|
8.8%
47/533
|
0.00%
0/14
|
5.5%
20/363
|
|
General disorders
Chills
|
8.5%
47/551
|
33.6%
179/533
|
21.4%
3/14
|
5.2%
19/363
|
|
General disorders
Fatigue
|
38.8%
214/551
|
66.4%
354/533
|
50.0%
7/14
|
28.7%
104/363
|
|
General disorders
Influenza like illness
|
6.9%
38/551
|
15.9%
85/533
|
21.4%
3/14
|
4.7%
17/363
|
|
General disorders
Local swelling
|
1.1%
6/551
|
0.19%
1/533
|
14.3%
2/14
|
0.83%
3/363
|
|
General disorders
Malaise
|
1.3%
7/551
|
7.7%
41/533
|
0.00%
0/14
|
1.7%
6/363
|
|
General disorders
Mucosal inflammation
|
1.1%
6/551
|
10.3%
55/533
|
0.00%
0/14
|
1.4%
5/363
|
|
General disorders
Oedema
|
8.3%
46/551
|
1.1%
6/533
|
0.00%
0/14
|
10.2%
37/363
|
|
General disorders
Oedema peripheral
|
24.3%
134/551
|
5.8%
31/533
|
0.00%
0/14
|
25.9%
94/363
|
|
General disorders
Pain
|
5.3%
29/551
|
9.8%
52/533
|
0.00%
0/14
|
3.9%
14/363
|
|
General disorders
Pyrexia
|
16.5%
91/551
|
40.7%
217/533
|
21.4%
3/14
|
11.6%
42/363
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/551
|
0.19%
1/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.91%
5/551
|
2.8%
15/533
|
7.1%
1/14
|
3.0%
11/363
|
|
Infections and infestations
Bronchitis
|
9.8%
54/551
|
7.5%
40/533
|
0.00%
0/14
|
9.4%
34/363
|
|
Infections and infestations
Cystitis
|
2.4%
13/551
|
1.3%
7/533
|
7.1%
1/14
|
2.8%
10/363
|
|
Infections and infestations
Gastroenteritis
|
6.4%
35/551
|
1.7%
9/533
|
0.00%
0/14
|
3.3%
12/363
|
|
Infections and infestations
Influenza
|
14.0%
77/551
|
6.2%
33/533
|
0.00%
0/14
|
8.0%
29/363
|
|
Infections and infestations
Nasopharyngitis
|
30.3%
167/551
|
8.8%
47/533
|
14.3%
2/14
|
23.1%
84/363
|
|
Infections and infestations
Pharyngitis
|
4.2%
23/551
|
4.5%
24/533
|
7.1%
1/14
|
3.0%
11/363
|
|
Infections and infestations
Rhinitis
|
7.6%
42/551
|
3.4%
18/533
|
0.00%
0/14
|
3.9%
14/363
|
|
Blood and lymphatic system disorders
Anaemia
|
11.6%
64/551
|
10.9%
58/533
|
0.00%
0/14
|
10.2%
37/363
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.7%
26/551
|
5.3%
28/533
|
14.3%
2/14
|
3.9%
14/363
|
|
Blood and lymphatic system disorders
Monocytopenia
|
0.00%
0/551
|
0.00%
0/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.5%
58/551
|
12.8%
68/533
|
7.1%
1/14
|
15.4%
56/363
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.36%
2/551
|
0.75%
4/533
|
14.3%
2/14
|
0.55%
2/363
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.7%
70/551
|
24.2%
129/533
|
28.6%
4/14
|
12.1%
44/363
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
1.3%
7/551
|
0.56%
3/533
|
7.1%
1/14
|
1.7%
6/363
|
|
Ear and labyrinth disorders
Deafness
|
0.36%
2/551
|
0.94%
5/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Ear and labyrinth disorders
Ear pain
|
3.1%
17/551
|
3.4%
18/533
|
7.1%
1/14
|
2.2%
8/363
|
|
Ear and labyrinth disorders
Vertigo
|
4.0%
22/551
|
7.3%
39/533
|
0.00%
0/14
|
4.4%
16/363
|
|
Endocrine disorders
Hypothyroidism
|
0.54%
3/551
|
2.1%
11/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Eye disorders
Conjunctivitis
|
8.3%
46/551
|
5.1%
27/533
|
0.00%
0/14
|
5.8%
21/363
|
|
Eye disorders
Dry eye
|
3.6%
20/551
|
3.0%
16/533
|
7.1%
1/14
|
3.0%
11/363
|
|
Eye disorders
Eye pain
|
2.5%
14/551
|
4.3%
23/533
|
7.1%
1/14
|
1.9%
7/363
|
|
Eye disorders
Eye swelling
|
9.1%
50/551
|
1.3%
7/533
|
0.00%
0/14
|
5.2%
19/363
|
|
Eye disorders
Eyelid oedema
|
8.9%
49/551
|
1.3%
7/533
|
0.00%
0/14
|
8.0%
29/363
|
|
Eye disorders
Growth of eyelashes
|
0.00%
0/551
|
0.00%
0/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Eye disorders
Lacrimation increased
|
7.6%
42/551
|
0.75%
4/533
|
0.00%
0/14
|
4.1%
15/363
|
|
Eye disorders
Periorbital oedema
|
29.9%
165/551
|
1.1%
6/533
|
0.00%
0/14
|
27.0%
98/363
|
|
Eye disorders
Retinal exudates
|
0.00%
0/551
|
0.38%
2/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.3%
40/551
|
1.9%
10/533
|
0.00%
0/14
|
4.4%
16/363
|
|
Gastrointestinal disorders
Abdominal pain
|
16.3%
90/551
|
11.6%
62/533
|
7.1%
1/14
|
15.4%
56/363
|
|
Gastrointestinal disorders
Abdominal pain upper
|
13.4%
74/551
|
12.0%
64/533
|
0.00%
0/14
|
10.5%
38/363
|
|
Gastrointestinal disorders
Constipation
|
11.4%
63/551
|
14.4%
77/533
|
14.3%
2/14
|
7.4%
27/363
|
|
Gastrointestinal disorders
Diarrhoea
|
45.4%
250/551
|
43.3%
231/533
|
14.3%
2/14
|
40.8%
148/363
|
|
Gastrointestinal disorders
Dry mouth
|
2.9%
16/551
|
10.9%
58/533
|
7.1%
1/14
|
2.5%
9/363
|
|
Gastrointestinal disorders
Dyspepsia
|
19.1%
105/551
|
8.3%
44/533
|
7.1%
1/14
|
14.6%
53/363
|
|
Gastrointestinal disorders
Flatulence
|
7.3%
40/551
|
1.5%
8/533
|
0.00%
0/14
|
4.4%
16/363
|
|
Gastrointestinal disorders
Gastric disorder
|
0.54%
3/551
|
0.56%
3/533
|
7.1%
1/14
|
1.4%
5/363
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.4%
35/551
|
2.4%
13/533
|
0.00%
0/14
|
5.8%
21/363
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.91%
5/551
|
3.6%
19/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Gastrointestinal disorders
Haemorrhoids
|
3.4%
19/551
|
2.3%
12/533
|
7.1%
1/14
|
1.7%
6/363
|
|
Gastrointestinal disorders
Mouth ulceration
|
1.3%
7/551
|
6.2%
33/533
|
7.1%
1/14
|
2.5%
9/363
|
|
Gastrointestinal disorders
Nausea
|
50.1%
276/551
|
61.0%
325/533
|
28.6%
4/14
|
38.0%
138/363
|
|
Gastrointestinal disorders
Sensitivity of teeth
|
0.00%
0/551
|
0.00%
0/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Gastrointestinal disorders
Stomatitis
|
2.0%
11/551
|
10.3%
55/533
|
0.00%
0/14
|
1.7%
6/363
|
|
Infections and infestations
Sinusitis
|
11.4%
63/551
|
6.0%
32/533
|
14.3%
2/14
|
8.0%
29/363
|
|
Infections and infestations
Upper respiratory tract infection
|
20.7%
114/551
|
8.4%
45/533
|
0.00%
0/14
|
13.8%
50/363
|
|
Infections and infestations
Urinary tract infection
|
6.5%
36/551
|
5.8%
31/533
|
0.00%
0/14
|
7.2%
26/363
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.54%
3/551
|
0.19%
1/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Injury, poisoning and procedural complications
Contusion
|
5.4%
30/551
|
2.8%
15/533
|
0.00%
0/14
|
3.9%
14/363
|
|
Injury, poisoning and procedural complications
Muscle injury
|
0.36%
2/551
|
0.00%
0/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Investigations
Alanine aminotransferase abnormal
|
0.18%
1/551
|
0.56%
3/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Investigations
Alanine aminotransferase increased
|
4.4%
24/551
|
5.8%
31/533
|
7.1%
1/14
|
3.0%
11/363
|
|
Investigations
Haemoglobin decreased
|
2.0%
11/551
|
1.7%
9/533
|
7.1%
1/14
|
2.5%
9/363
|
|
Investigations
Platelet count decreased
|
0.73%
4/551
|
1.5%
8/533
|
7.1%
1/14
|
2.2%
8/363
|
|
Investigations
Weight decreased
|
4.7%
26/551
|
17.1%
91/533
|
7.1%
1/14
|
3.9%
14/363
|
|
Investigations
Weight increased
|
15.6%
86/551
|
2.6%
14/533
|
7.1%
1/14
|
14.3%
52/363
|
|
Investigations
White blood cell count increased
|
0.54%
3/551
|
1.5%
8/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/551
|
0.00%
0/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.6%
53/551
|
38.8%
207/533
|
14.3%
2/14
|
5.0%
18/363
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
7/551
|
2.1%
11/533
|
7.1%
1/14
|
0.28%
1/363
|
|
Metabolism and nutrition disorders
Fluid retention
|
5.3%
29/551
|
0.56%
3/533
|
0.00%
0/14
|
4.1%
15/363
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.7%
37/551
|
2.3%
12/533
|
0.00%
0/14
|
6.1%
22/363
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.00%
0/551
|
0.00%
0/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
31.4%
173/551
|
37.3%
199/533
|
21.4%
3/14
|
25.6%
93/363
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
24.9%
137/551
|
19.7%
105/533
|
14.3%
2/14
|
16.3%
59/363
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.5%
58/551
|
14.6%
78/533
|
14.3%
2/14
|
7.7%
28/363
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
49.4%
272/551
|
11.8%
63/533
|
7.1%
1/14
|
46.3%
168/363
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.2%
34/551
|
5.6%
30/533
|
7.1%
1/14
|
5.2%
19/363
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
23.8%
131/551
|
37.5%
200/533
|
28.6%
4/14
|
17.4%
63/363
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.7%
26/551
|
2.1%
11/533
|
7.1%
1/14
|
4.1%
15/363
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
19.4%
107/551
|
16.7%
89/533
|
0.00%
0/14
|
14.6%
53/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
|
0.36%
2/551
|
0.00%
0/533
|
7.1%
1/14
|
0.28%
1/363
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.18%
1/551
|
0.19%
1/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Nervous system disorders
Ageusia
|
0.18%
1/551
|
0.75%
4/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Nervous system disorders
Amnesia
|
1.8%
10/551
|
6.6%
35/533
|
0.00%
0/14
|
2.5%
9/363
|
|
Nervous system disorders
Disturbance in attention
|
1.3%
7/551
|
6.9%
37/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Nervous system disorders
Dizziness
|
19.1%
105/551
|
23.3%
124/533
|
21.4%
3/14
|
11.8%
43/363
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/551
|
0.56%
3/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/551
|
0.38%
2/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Nervous system disorders
Dysgeusia
|
3.1%
17/551
|
9.0%
48/533
|
7.1%
1/14
|
2.2%
8/363
|
|
Nervous system disorders
Headache
|
37.2%
205/551
|
43.3%
231/533
|
14.3%
2/14
|
24.0%
87/363
|
|
Nervous system disorders
Lethargy
|
2.0%
11/551
|
6.8%
36/533
|
0.00%
0/14
|
0.83%
3/363
|
|
Nervous system disorders
Memory impairment
|
0.73%
4/551
|
1.7%
9/533
|
7.1%
1/14
|
0.83%
3/363
|
|
Nervous system disorders
Migraine
|
2.5%
14/551
|
1.1%
6/533
|
7.1%
1/14
|
1.9%
7/363
|
|
Nervous system disorders
Neuropathy peripheral
|
2.5%
14/551
|
4.5%
24/533
|
7.1%
1/14
|
3.0%
11/363
|
|
Nervous system disorders
Paraesthesia
|
9.1%
50/551
|
7.3%
39/533
|
0.00%
0/14
|
7.4%
27/363
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.73%
4/551
|
0.56%
3/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Psychiatric disorders
Anxiety
|
9.4%
52/551
|
11.3%
60/533
|
21.4%
3/14
|
4.7%
17/363
|
|
Psychiatric disorders
Depression
|
15.2%
84/551
|
34.9%
186/533
|
21.4%
3/14
|
8.5%
31/363
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/551
|
0.19%
1/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Psychiatric disorders
Insomnia
|
15.1%
83/551
|
18.6%
99/533
|
0.00%
0/14
|
8.5%
31/363
|
|
Psychiatric disorders
Mood altered
|
0.54%
3/551
|
4.1%
22/533
|
7.1%
1/14
|
0.55%
2/363
|
|
Psychiatric disorders
Nervousness
|
1.6%
9/551
|
1.3%
7/533
|
7.1%
1/14
|
1.7%
6/363
|
|
Renal and urinary disorders
Dysuria
|
2.0%
11/551
|
2.8%
15/533
|
14.3%
2/14
|
1.4%
5/363
|
|
Renal and urinary disorders
Polyuria
|
0.36%
2/551
|
0.38%
2/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Reproductive system and breast disorders
Prostatitis
|
0.54%
3/551
|
0.19%
1/533
|
7.1%
1/14
|
0.00%
0/363
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.1%
111/551
|
22.9%
122/533
|
28.6%
4/14
|
14.9%
54/363
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.36%
2/551
|
1.3%
7/533
|
7.1%
1/14
|
0.28%
1/363
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
50/551
|
14.1%
75/533
|
7.1%
1/14
|
9.1%
33/363
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.6%
20/551
|
7.9%
42/533
|
0.00%
0/14
|
1.9%
7/363
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
18.1%
100/551
|
11.4%
61/533
|
21.4%
3/14
|
6.9%
25/363
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
2.7%
15/551
|
3.8%
20/533
|
7.1%
1/14
|
1.9%
7/363
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
1.3%
7/551
|
0.94%
5/533
|
7.1%
1/14
|
0.28%
1/363
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.4%
30/551
|
23.5%
125/533
|
14.3%
2/14
|
3.3%
12/363
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.3%
46/551
|
8.3%
44/533
|
7.1%
1/14
|
5.5%
20/363
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.3%
40/551
|
4.3%
23/533
|
0.00%
0/14
|
3.6%
13/363
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.0%
33/551
|
14.8%
79/533
|
0.00%
0/14
|
5.5%
20/363
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
10.0%
55/551
|
15.8%
84/533
|
14.3%
2/14
|
7.4%
27/363
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.6%
53/551
|
11.8%
63/533
|
0.00%
0/14
|
6.6%
24/363
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.9%
154/551
|
17.1%
91/533
|
0.00%
0/14
|
21.5%
78/363
|
|
Vascular disorders
Haematoma
|
1.6%
9/551
|
1.5%
8/533
|
14.3%
2/14
|
1.7%
6/363
|
|
Vascular disorders
Hypertension
|
9.1%
50/551
|
3.0%
16/533
|
0.00%
0/14
|
6.3%
23/363
|
|
Vascular disorders
Peripheral coldness
|
0.73%
4/551
|
1.3%
7/533
|
7.1%
1/14
|
0.55%
2/363
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER