Trial Outcomes & Findings for Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity) (NCT NCT00124748)
NCT ID: NCT00124748
Last Updated: 2012-02-03
Results Overview
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
476 participants
Primary outcome timeframe
12 months
Results posted on
2012-02-03
Participant Flow
Participant milestones
| Measure |
Imatinib 400 mg
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
157
|
319
|
|
Overall Study
Safety Population
|
157
|
316
|
|
Overall Study
COMPLETED
|
14
|
35
|
|
Overall Study
NOT COMPLETED
|
143
|
284
|
Reasons for withdrawal
| Measure |
Imatinib 400 mg
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Overall Study
Adverse Event
|
8
|
39
|
|
Overall Study
Abnormal laboratory Value
|
2
|
2
|
|
Overall Study
Abnormal Procedure
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
20
|
41
|
|
Overall Study
No longer requires study drug
|
1
|
1
|
|
Overall Study
Protocol Violation
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
15
|
|
Overall Study
Lost to Follow-up
|
2
|
7
|
|
Overall Study
Administrative Problem(Study Terminated)
|
101
|
174
|
|
Overall Study
Death
|
1
|
3
|
Baseline Characteristics
Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)
Baseline characteristics by cohort
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
Total
n=476 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
46.2 years
STANDARD_DEVIATION 14.90 • n=5 Participants
|
48.2 years
STANDARD_DEVIATION 13.89 • n=7 Participants
|
47.6 years
STANDARD_DEVIATION 14.25 • n=5 Participants
|
|
Sex: Female, Male
Female
|
73 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
209 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
84 Participants
n=5 Participants
|
183 Participants
n=7 Participants
|
267 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months
|
38.9 Percentage of participants
|
45.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 24, 36 and 42 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
24 months
|
53.5 Percentage of participants
|
50.8 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
36 months
|
52.2 Percentage of participants
|
49.8 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
42 months
|
51.6 Percentage of participants
|
50.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 12, 24, 36, 42 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Cytogenetic response (CyR)is the percentage of Philadelphia chromosome positive metaphases (among at least 20 metaphase cells in bone marrow (BM)) with Complete Cytogenetic Response (CCyR) being 0 percent.
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
12 months
|
66.9 Percentage of Participants
|
70.2 Percentage of Participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
24 months
|
76.4 Percentage of Participants
|
76.8 Percentage of Participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
36 months
|
79.0 Percentage of Participants
|
80.6 Percentage of Participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
42 months
|
80.3 Percentage of Participants
|
81.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: 12, 24, 36, and 42 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Complete Hematologic Response (CHR) is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) \< 5% in PB and No evidence of extramedullary involvement.
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
12 months
|
94.9 Percentage of participants
|
93.7 Percentage of participants
|
|
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
24 months
|
94.9 Percentage of participants
|
93.7 Percentage of participants
|
|
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
36 months
|
96.2 Percentage of participants
|
94.4 Percentage of participants
|
|
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
42 months
|
96.2 Percentage of participants
|
94.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 , 24, 36 and 42 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who were randomized into the study.
"Undetectable levels" or Complete molecular response is defined as Bcr-Abl ratio (%) on international scale (IS) \<= 0.0032% (≥ 4.5 log reduction of BCR-Abl transcripts from a standardized baseline).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
42 Months
|
14.6 Percentage of Partcipants
|
12.5 Percentage of Partcipants
|
|
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
12 Months
|
4.5 Percentage of Partcipants
|
4.7 Percentage of Partcipants
|
|
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
24 Months
|
11.5 Percentage of Partcipants
|
10.3 Percentage of Partcipants
|
|
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
36 Months
|
12.7 Percentage of Partcipants
|
13.2 Percentage of Partcipants
|
SECONDARY outcome
Timeframe: 42 months overallPopulation: Intent-to-treat (ITT) population consisted of all patients who were randomized to the study treatment.
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region \[Bcr\] gene and Abelson proto-oncogene \[Abl\] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction \[RT-PCR\] (performed centrally). Time to MMR (months) = (date of first MMR or censoring - date of randomization + 1) / 30.4375. Time to first MMR was evaluated using the Kaplan-Meier method
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Time to First Major Molecular Response
|
13.6 Months
Interval 10.8 to 15.6
|
8.4 Months
Interval 8.3 to 9.0
|
SECONDARY outcome
Timeframe: 60 months overallPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Cytogenetic response (CyR) is the percentage of Philadelphia positive metaphases (among at least 20 metaphase cells in Bone Marrow) with Complete Cytogenetic Response (CCyR) being 0 percent. Time to CCyR (months) = (date of first CCyR or censoring - date of randomization + 1) / 30.4375. Time to first CCyR was evaluated using the Kaplan-Meier method.
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Time to First Complete Cytogenetic Response
|
10.8 Months
Interval 5.9 to 11.2
|
5.8 Months
Interval 5.8 to 6.0
|
SECONDARY outcome
Timeframe: 60 months overallPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Complete Hematological Response (CHR) is defined is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) \< 5% in PB and No evidence of extramedullary involvement. Time to CHR (months) = (date of first CHR or censoring - date of randomization + 1) / 30.4375. Time to first CHR was evaluated using the Kaplan-Meier method.
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Time to First Complete Hematological Response (CHR)]
|
1.0 Months
Interval 1.0 to 1.0
|
1.0 Months
Interval 1.0 to 1.0
|
SECONDARY outcome
Timeframe: 60 months over allPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
EFS on treatment was defined as time between randomization and either (1) death due to any cause during study treatment, (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment, (3) loss of complete hematological response (CHR), or (4) loss of major cytogenic response (MCyR) while on treatment. Estimated rate of EFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
12 Months
|
95.3 Percent probability
Interval 90.5 to 97.7
|
98.0 Percent probability
Interval 95.6 to 99.1
|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
24 Months
|
94.6 Percent probability
Interval 89.5 to 97.3
|
95.3 Percent probability
Interval 92.1 to 97.3
|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
36 Months
|
92.3 Percent probability
Interval 86.5 to 95.7
|
94.5 Percent probability
Interval 91.1 to 96.7
|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
42 Months
|
92.3 Percent probability
Interval 86.5 to 95.7
|
94.1 Percent probability
Interval 90.5 to 96.3
|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
48 Months
|
92.3 Percent probability
Interval 86.5 to 95.7
|
93.6 Percent probability
Interval 89.9 to 96.0
|
|
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
60 Months
|
90.3 Percent probability
Interval 82.7 to 94.7
|
93.6 Percent probability
Interval 89.9 to 96.0
|
SECONDARY outcome
Timeframe: 60 months over all and follow up periodPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
PFS on study which was defined as time between randomization and either (1) death due to any cause on treatment of during follow-up after discontinuation of treatment or (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment during follow-up after discontinuation of study treatment. Estimated rate of PFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
12 Months
|
97.4 Percent probability
Interval 93.2 to 99.0
|
98.7 Percent probability
Interval 96.5 to 99.5
|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
24 Months
|
95.9 Percent probability
Interval 91.2 to 98.2
|
97.5 Percent probability
Interval 94.9 to 98.8
|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
36 Months
|
94.4 Percent probability
Interval 89.0 to 97.1
|
96.7 Percent probability
Interval 93.7 to 98.3
|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
42 Months
|
94.4 Percent probability
Interval 89.0 to 97.1
|
96.3 Percent probability
Interval 93.2 to 98.0
|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
48 Months
|
94.4 Percent probability
Interval 89.0 to 97.1
|
95.8 Percent probability
Interval 92.5 to 97.7
|
|
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
60 Months
|
94.4 Percent probability
Interval 89.0 to 97.1
|
95.8 Percent probability
Interval 92.5 to 97.7
|
SECONDARY outcome
Timeframe: 60 months over all and follow up periodPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
(Accelerated Phase/Blast Crisis) AP/BC was defined as time between randomization and either (1) (Chronic Myeloid Leukemia) CML-related death (if death was primary reason for discontinuation) or (2) progression to AP or BC (during treatment). Estimated rate of AC/BC was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
12 Months
|
97.4 Percent probability
Interval 93.2 to 99.0
|
99.0 Percent probability
Interval 97.0 to 99.7
|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
24 Months
|
95.9 Percent probability
Interval 91.2 to 98.2
|
97.9 Percent probability
Interval 95.3 to 99.0
|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
36 Months
|
95.2 Percent probability
Interval 90.1 to 97.7
|
97.5 Percent probability
Interval 94.7 to 98.8
|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
42 Months
|
95.2 Percent probability
Interval 90.1 to 97.7
|
97.0 Percent probability
Interval 94.1 to 98.5
|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
48 Months
|
95.2 Percent probability
Interval 90.1 to 97.7
|
97.0 Percent probability
Interval 94.1 to 98.5
|
|
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
60 Months
|
95.2 Percent probability
Interval 90.1 to 97.7
|
97.0 Percent probability
Interval 94.1 to 98.5
|
SECONDARY outcome
Timeframe: 60 months over all and follow up periodPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
OS was defined as time between randomization and death due to any cause during study treatment or during follow-up after discontinuation of treatment. Estimated rate of OS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
12 Months
|
98.7 Percent probability
Interval 94.9 to 99.7
|
99.0 Percent probability
Interval 97.1 to 99.7
|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
24 Months
|
97.4 Percent probability
Interval 93.2 to 99.0
|
97.8 Percent probability
Interval 95.4 to 98.9
|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
36 Months
|
96.1 Percent probability
Interval 91.4 to 98.2
|
95.5 Percent probability
Interval 92.5 to 97.3
|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
42 Months
|
94.7 Percent probability
Interval 89.7 to 97.2
|
94.8 Percent probability
Interval 91.6 to 96.8
|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
48 Months
|
94.0 Percent probability
Interval 88.7 to 96.8
|
93.4 Percent probability
Interval 89.7 to 95.8
|
|
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
60 Months
|
94.0 Percent probability
Interval 88.7 to 96.8
|
93.4 Percent probability
Interval 89.7 to 95.8
|
SECONDARY outcome
Timeframe: From First major molecular response to first confirmed loss or censoringPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Duration of MMR (months) = (date of first confirmed loss or censoring - date of MMR + 1 ) / 30.4375. Estimated rate of duration of first MMR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
36 Months
|
85.1 Percent probability
Interval 75.6 to 91.1
|
81.1 Percent probability
Interval 75.1 to 85.8
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
3 Months
|
100 Percent probability
Interval 100.0 to 100.0
|
96.3 Percent probability
Interval 92.9 to 98.0
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
6 Months
|
98.3 Percent probability
Interval 93.3 to 99.6
|
90.7 Percent probability
Interval 86.2 to 93.8
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
9 Months
|
97.4 Percent probability
Interval 92.2 to 99.2
|
90.2 Percent probability
Interval 85.7 to 93.4
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
12 Months
|
95.6 Percent probability
Interval 89.8 to 98.2
|
88.4 Percent probability
Interval 83.6 to 91.9
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
15 Months
|
93.8 Percent probability
Interval 87.4 to 97.0
|
87.5 Percent probability
Interval 82.5 to 91.2
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
18 Months
|
92.8 Percent probability
Interval 86.2 to 96.4
|
86.1 Percent probability
Interval 80.9 to 90.0
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
21 Months
|
90.9 Percent probability
Interval 83.8 to 95.0
|
85.1 Percent probability
Interval 79.8 to 89.1
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
24 Months
|
89.9 Percent probability
Interval 82.5 to 94.3
|
83.6 Percent probability
Interval 78.0 to 87.8
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
30 Months
|
88.5 Percent probability
Interval 80.5 to 93.4
|
82.5 Percent probability
Interval 76.8 to 86.9
|
|
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
42 Months
|
85.1 Percent probability
Interval 75.6 to 91.1
|
77.9 Percent probability
Interval 70.4 to 83.8
|
SECONDARY outcome
Timeframe: From first complete cytogenetic response to first confirmed loss or censoringPopulation: Intent-to-treat (ITT) population consisted of all patients who are randomized into the study.
Duration of CCyR was defined as the time between date of CCyR and the earliest of either (1) loss of CCyR OR (2) (Chronic Myeloid Leukemia) CML-related death or progression to (Accelerated Phase/Blast Crisis) AP/BC during study treatment. Estimated rate of duration of first CCyR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=319 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
12 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
97.8 Percent probability
Interval 94.7 to 99.1
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
18 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
97.3 Percent probability
Interval 94.1 to 98.8
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
24 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
96.8 Percent probability
Interval 93.3 to 98.4
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
30 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
96.8 Percent probability
Interval 93.3 to 98.4
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
36 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
95.9 Percent probability
Interval 91.9 to 98.0
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
42 Months
|
98.2 Percent probability
Interval 93.1 to 99.6
|
95.9 Percent probability
Interval 91.9 to 98.0
|
|
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
6 Months
|
99.1 Percent probability
Interval 94.0 to 99.9
|
99.2 Percent probability
Interval 96.7 to 99.8
|
SECONDARY outcome
Timeframe: start of treatment to Month 36Population: Safety analysis population (SAP): consisted of all patients who received at least one dose of study medication.Subjects are summarized according to the safety treatment allocation (the dose they actually received).
The mean actual dose intensity per day from start of treatment up to last dose or discontinuation was evaluated up to Month 36. Actual dose intensity (mg/day) = total dose/time on treatment (periods of zero dose are included)
Outcome measures
| Measure |
Imatinib 400 mg
n=157 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=316 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Mean Actual Dose Intensity Per Day
|
399.3 mg/day
Standard Deviation 83.84
|
643.3 mg/day
Standard Deviation 158.63
|
SECONDARY outcome
Timeframe: Month 12Population: Pharmakokinetic (PK) population consisted of number of patients with a pre-dose PK sample at Month 12
Imatinib PK trough plasma concentration (Cmin) was defined as any pre-dose Imatinib plasma concentration
Outcome measures
| Measure |
Imatinib 400 mg
n=86 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=150 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
|
1458.2 mg/mL
Standard Deviation 2259.5
|
739.58 mg/mL
Standard Deviation 1321.09
|
SECONDARY outcome
Timeframe: 42 monthsPopulation: Intent-to-treat (ITT) population consisted of all patients who were randomized to the study treatment. Patients without a valid polymerase chain reaction (PCR) assessment or those who had experienced an event before the landmark were excluded from analysis
A Landmark Kaplan-Meier analysis was performed for PFS at 42 months by MMR status at 6, 12, and 18 months to investigate their prognostic value.
Outcome measures
| Measure |
Imatinib 400 mg
n=134 Participants
Oral dose of 400mg Imatinib once daily (q.d.). All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800 mg
n=274 Participants
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
No MMR at 6 Months
|
94.8 Percent probability
Interval 88.0 to 97.8
|
95.6 Percent probability
Interval 90.3 to 98.0
|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
MMR at 6 Months
|
100 Percent probability
Interval 100.0 to 100.0
|
99.0 Percent probability
Interval 93.2 to 99.9
|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
No MMR at 12 Months
|
93.2 Percent probability
Interval 82.9 to 97.4
|
94.6 Percent probability
Interval 87.4 to 97.7
|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
MMR at 12 Months
|
100 Percent probability
Interval 100.0 to 100.0
|
99.3 Percent probability
Interval 95.0 to 99.9
|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
No MMR at 18 Months
|
96.7 Percent probability
Interval 78.6 to 99.5
|
97.0 Percent probability
Interval 88.6 to 99.3
|
|
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
MMR at 18 Months
|
98.7 Percent probability
Interval 91.2 to 99.8
|
99.3 Percent probability
Interval 95.2 to 99.9
|
SECONDARY outcome
Timeframe: 48 months overallPopulation: This analysis was not done because no major molecular improvement was observed in the 800mg dose compared to 400mg dose. Hence, analysis for complete molecular response was not necessary.
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 monthsPopulation: Due to the small number of diabetic patients enrolled into the study, the analysis was never done.
Outcome measures
Outcome data not reported
Adverse Events
Imatinib 400mg
Serious events: 42 serious events
Other events: 157 other events
Deaths: 0 deaths
Imatinib 800mg
Serious events: 121 serious events
Other events: 315 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Imatinib 400mg
n=157 participants at risk
Oral dose of 400mg imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800mg
n=316 participants at risk
Patients randomized to receive 800 mg imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.9%
3/157
|
1.9%
6/316
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
2/157
|
1.6%
5/316
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
0.00%
0/157
|
0.32%
1/316
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/157
|
0.63%
2/316
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.2%
5/157
|
3.8%
12/316
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.64%
1/157
|
0.32%
1/316
|
|
Blood and lymphatic system disorders
Splenic cyst
|
0.00%
0/157
|
0.32%
1/316
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.5%
4/157
|
2.8%
9/316
|
|
Cardiac disorders
Angina pectoris
|
1.3%
2/157
|
0.00%
0/316
|
|
Cardiac disorders
Arrhythmia supraventricular
|
0.00%
0/157
|
0.32%
1/316
|
|
Cardiac disorders
Atrial fibrillation
|
0.64%
1/157
|
0.95%
3/316
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/157
|
0.32%
1/316
|
|
Cardiac disorders
Cardiac discomfort
|
0.00%
0/157
|
0.32%
1/316
|
|
Cardiac disorders
Cardiac failure congestive
|
0.64%
1/157
|
0.32%
1/316
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/157
|
0.32%
1/316
|
|
Cardiac disorders
Coronary artery occlusion
|
0.64%
1/157
|
0.00%
0/316
|
|
Cardiac disorders
Myocardial infarction
|
0.64%
1/157
|
0.32%
1/316
|
|
Cardiac disorders
Palpitations
|
0.00%
0/157
|
0.32%
1/316
|
|
Congenital, familial and genetic disorders
Phimosis
|
0.64%
1/157
|
0.00%
0/316
|
|
Ear and labyrinth disorders
Deafness
|
0.00%
0/157
|
0.32%
1/316
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.00%
0/157
|
0.32%
1/316
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/157
|
0.32%
1/316
|
|
Ear and labyrinth disorders
Vertigo
|
0.64%
1/157
|
0.00%
0/316
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Amaurosis
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Glaucoma
|
0.00%
0/157
|
0.63%
2/316
|
|
Eye disorders
Retinal detachment
|
0.00%
0/157
|
0.63%
2/316
|
|
Eye disorders
Retinal haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Retinal vein occlusion
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Uveitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Eye disorders
Vitreous haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Abdominal pain
|
0.64%
1/157
|
0.95%
3/316
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/157
|
0.95%
3/316
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Anal polyp
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Caecitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/157
|
0.95%
3/316
|
|
Gastrointestinal disorders
Diarrhoea
|
0.64%
1/157
|
1.3%
4/316
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Enterovesical fistula
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/157
|
0.63%
2/316
|
|
Gastrointestinal disorders
Gastritis alcoholic
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/157
|
0.95%
3/316
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/157
|
0.63%
2/316
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/157
|
0.95%
3/316
|
|
Gastrointestinal disorders
Reflux gastritis
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/157
|
0.63%
2/316
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Gastrointestinal disorders
Vomiting
|
0.64%
1/157
|
1.3%
4/316
|
|
General disorders
Adverse drug reaction
|
0.64%
1/157
|
0.00%
0/316
|
|
General disorders
Asthenia
|
0.00%
0/157
|
0.63%
2/316
|
|
General disorders
Chest discomfort
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Chest pain
|
1.3%
2/157
|
0.00%
0/316
|
|
General disorders
Concomitant disease progression
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Death
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Device ineffective
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Mucosal inflammation
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Polyp
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Polyserositis
|
0.00%
0/157
|
0.32%
1/316
|
|
General disorders
Pyrexia
|
1.9%
3/157
|
4.1%
13/316
|
|
Hepatobiliary disorders
Bile duct stone
|
0.64%
1/157
|
0.00%
0/316
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/157
|
0.32%
1/316
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.64%
1/157
|
0.63%
2/316
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/157
|
0.63%
2/316
|
|
Hepatobiliary disorders
Liver disorder
|
0.64%
1/157
|
0.32%
1/316
|
|
Infections and infestations
Appendicitis
|
0.00%
0/157
|
1.6%
5/316
|
|
Infections and infestations
Bacterial infection
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Cellulitis
|
0.00%
0/157
|
0.63%
2/316
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/157
|
0.95%
3/316
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Febrile infection
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Gastroenteritis
|
1.3%
2/157
|
1.6%
5/316
|
|
Infections and infestations
Gastroenteritis viral
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
HIV infection
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Haematoma infection
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Infection
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Influenza
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Meningitis
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Pharyngotonsillitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Pneumonia
|
1.3%
2/157
|
1.6%
5/316
|
|
Infections and infestations
Pneumonia pneumococcal
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Pyelonephritis
|
0.64%
1/157
|
0.32%
1/316
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Retroperitoneal abscess
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Salmonellosis
|
0.00%
0/157
|
0.63%
2/316
|
|
Infections and infestations
Sepsis
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Septic shock
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Sinusitis
|
0.64%
1/157
|
0.00%
0/316
|
|
Infections and infestations
Tooth infection
|
0.00%
0/157
|
0.32%
1/316
|
|
Infections and infestations
Upper respiratory tract infection
|
0.64%
1/157
|
0.63%
2/316
|
|
Infections and infestations
Urinary tract infection
|
0.64%
1/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.3%
2/157
|
0.00%
0/316
|
|
Injury, poisoning and procedural complications
Drug exposure during pregnancy
|
0.64%
1/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Fall
|
1.3%
2/157
|
0.63%
2/316
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.64%
1/157
|
0.00%
0/316
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.64%
1/157
|
0.00%
0/316
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/157
|
0.32%
1/316
|
|
Investigations
Alanine aminotransferase increased
|
0.64%
1/157
|
0.32%
1/316
|
|
Investigations
Aspartate aminotransferase increased
|
0.64%
1/157
|
0.32%
1/316
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.00%
0/157
|
0.32%
1/316
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/157
|
0.32%
1/316
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/157
|
0.63%
2/316
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/157
|
0.32%
1/316
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/157
|
0.32%
1/316
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/157
|
0.32%
1/316
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.64%
1/157
|
0.95%
3/316
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/157
|
0.95%
3/316
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/157
|
0.32%
1/316
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/157
|
0.32%
1/316
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.64%
1/157
|
0.63%
2/316
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.64%
1/157
|
0.00%
0/316
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.64%
1/157
|
0.00%
0/316
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/157
|
0.63%
2/316
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/157
|
0.63%
2/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast crisis in myelogenous leukaemia
|
1.3%
2/157
|
0.63%
2/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Desmoid tumour
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.64%
1/157
|
0.00%
0/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mycosis fungoides
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/157
|
1.6%
5/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sarcoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid adenoma
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/157
|
0.32%
1/316
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.64%
1/157
|
0.32%
1/316
|
|
Nervous system disorders
Cerebral infarction
|
0.64%
1/157
|
0.00%
0/316
|
|
Nervous system disorders
Cervical myelopathy
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Dizziness
|
0.64%
1/157
|
0.00%
0/316
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Headache
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
IIIrd nerve paralysis
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Migraine
|
0.64%
1/157
|
0.32%
1/316
|
|
Nervous system disorders
Nerve root compression
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/157
|
0.95%
3/316
|
|
Nervous system disorders
Parkinsonism
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Radiculopathy
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
Syncope
|
0.00%
0/157
|
0.95%
3/316
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/157
|
0.32%
1/316
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.64%
1/157
|
0.00%
0/316
|
|
Pregnancy, puerperium and perinatal conditions
Abortion incomplete
|
0.00%
0/157
|
0.32%
1/316
|
|
Pregnancy, puerperium and perinatal conditions
Neonatal disorder
|
0.00%
0/157
|
0.32%
1/316
|
|
Pregnancy, puerperium and perinatal conditions
Placental disorder
|
0.00%
0/157
|
0.32%
1/316
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/157
|
0.63%
2/316
|
|
Pregnancy, puerperium and perinatal conditions
Premature labour
|
0.64%
1/157
|
0.00%
0/316
|
|
Psychiatric disorders
Confusional state
|
0.64%
1/157
|
0.00%
0/316
|
|
Psychiatric disorders
Depression
|
0.00%
0/157
|
0.63%
2/316
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/157
|
0.95%
3/316
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Paroxysmal nocturnal haemoglobinuria
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/157
|
0.32%
1/316
|
|
Renal and urinary disorders
Urethral disorder
|
0.64%
1/157
|
0.00%
0/316
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.00%
0/157
|
0.32%
1/316
|
|
Reproductive system and breast disorders
Endometriosis
|
0.64%
1/157
|
0.00%
0/316
|
|
Reproductive system and breast disorders
Haemorrhagic ovarian cyst
|
0.64%
1/157
|
0.00%
0/316
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.64%
1/157
|
0.00%
0/316
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.64%
1/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.64%
1/157
|
1.3%
4/316
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.64%
1/157
|
0.00%
0/316
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.64%
1/157
|
0.00%
0/316
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/157
|
0.32%
1/316
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/157
|
0.32%
1/316
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/157
|
0.63%
2/316
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.64%
1/157
|
0.00%
0/316
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/157
|
1.3%
4/316
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/157
|
0.32%
1/316
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/157
|
0.32%
1/316
|
|
Skin and subcutaneous tissue disorders
Toxic skin eruption
|
0.00%
0/157
|
0.32%
1/316
|
|
Social circumstances
Pregnancy of partner
|
1.3%
2/157
|
0.63%
2/316
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/157
|
0.32%
1/316
|
|
Vascular disorders
Extremity necrosis
|
0.64%
1/157
|
0.00%
0/316
|
|
Vascular disorders
Haematoma
|
0.64%
1/157
|
0.00%
0/316
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/157
|
0.32%
1/316
|
|
Vascular disorders
Hypotension
|
0.00%
0/157
|
0.32%
1/316
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/157
|
0.32%
1/316
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/157
|
0.32%
1/316
|
|
Vascular disorders
Peripheral vascular disorder
|
0.64%
1/157
|
0.00%
0/316
|
|
Vascular disorders
Vasculitis
|
0.00%
0/157
|
0.32%
1/316
|
Other adverse events
| Measure |
Imatinib 400mg
n=157 participants at risk
Oral dose of 400mg imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
|
Imatinib 800mg
n=316 participants at risk
Patients randomized to receive 800 mg imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
26.1%
41/157
|
38.0%
120/316
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.7%
20/157
|
16.1%
51/316
|
|
Blood and lymphatic system disorders
Neutropenia
|
24.2%
38/157
|
33.9%
107/316
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
22.9%
36/157
|
35.1%
111/316
|
|
Eye disorders
Conjunctival haemorrhage
|
5.1%
8/157
|
6.0%
19/316
|
|
Eye disorders
Conjunctivitis
|
5.7%
9/157
|
6.0%
19/316
|
|
Eye disorders
Eye swelling
|
1.9%
3/157
|
6.0%
19/316
|
|
Eye disorders
Eyelid oedema
|
13.4%
21/157
|
14.2%
45/316
|
|
Eye disorders
Lacrimation increased
|
5.1%
8/157
|
9.5%
30/316
|
|
Eye disorders
Periorbital oedema
|
29.3%
46/157
|
41.8%
132/316
|
|
Gastrointestinal disorders
Abdominal discomfort
|
8.3%
13/157
|
5.4%
17/316
|
|
Gastrointestinal disorders
Abdominal distension
|
5.7%
9/157
|
4.7%
15/316
|
|
Gastrointestinal disorders
Abdominal pain
|
22.9%
36/157
|
24.1%
76/316
|
|
Gastrointestinal disorders
Abdominal pain upper
|
24.2%
38/157
|
17.1%
54/316
|
|
Gastrointestinal disorders
Constipation
|
12.1%
19/157
|
11.4%
36/316
|
|
Gastrointestinal disorders
Diarrhoea
|
45.2%
71/157
|
58.2%
184/316
|
|
Gastrointestinal disorders
Dyspepsia
|
13.4%
21/157
|
18.0%
57/316
|
|
Gastrointestinal disorders
Flatulence
|
4.5%
7/157
|
6.3%
20/316
|
|
Gastrointestinal disorders
Gastritis
|
3.8%
6/157
|
6.3%
20/316
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
3.2%
5/157
|
8.9%
28/316
|
|
Gastrointestinal disorders
Haemorrhoids
|
3.8%
6/157
|
7.9%
25/316
|
|
Gastrointestinal disorders
Nausea
|
49.7%
78/157
|
64.9%
205/316
|
|
Gastrointestinal disorders
Toothache
|
8.9%
14/157
|
6.6%
21/316
|
|
Gastrointestinal disorders
Vomiting
|
34.4%
54/157
|
44.3%
140/316
|
|
General disorders
Asthenia
|
14.0%
22/157
|
15.2%
48/316
|
|
General disorders
Chest pain
|
5.7%
9/157
|
2.2%
7/316
|
|
General disorders
Chills
|
5.7%
9/157
|
5.7%
18/316
|
|
General disorders
Face oedema
|
8.3%
13/157
|
20.3%
64/316
|
|
General disorders
Fatigue
|
32.5%
51/157
|
41.5%
131/316
|
|
General disorders
Influenza like illness
|
7.6%
12/157
|
11.1%
35/316
|
|
General disorders
Oedema
|
6.4%
10/157
|
11.1%
35/316
|
|
General disorders
Oedema peripheral
|
27.4%
43/157
|
42.7%
135/316
|
|
General disorders
Pyrexia
|
19.7%
31/157
|
23.7%
75/316
|
|
Infections and infestations
Bronchitis
|
6.4%
10/157
|
8.2%
26/316
|
|
Infections and infestations
Gastroenteritis
|
5.1%
8/157
|
8.2%
26/316
|
|
Infections and infestations
Influenza
|
10.8%
17/157
|
5.7%
18/316
|
|
Infections and infestations
Nasopharyngitis
|
12.1%
19/157
|
9.5%
30/316
|
|
Infections and infestations
Pharyngitis
|
3.2%
5/157
|
5.4%
17/316
|
|
Infections and infestations
Sinusitis
|
8.3%
13/157
|
10.4%
33/316
|
|
Infections and infestations
Upper respiratory tract infection
|
28.0%
44/157
|
27.8%
88/316
|
|
Infections and infestations
Urinary tract infection
|
10.8%
17/157
|
8.2%
26/316
|
|
Injury, poisoning and procedural complications
Contusion
|
3.8%
6/157
|
5.7%
18/316
|
|
Injury, poisoning and procedural complications
Procedural pain
|
4.5%
7/157
|
5.1%
16/316
|
|
Investigations
Alanine aminotransferase increased
|
7.0%
11/157
|
7.9%
25/316
|
|
Investigations
Aspartate aminotransferase increased
|
7.0%
11/157
|
8.2%
26/316
|
|
Investigations
Platelet count decreased
|
0.64%
1/157
|
5.7%
18/316
|
|
Investigations
Weight decreased
|
3.8%
6/157
|
8.2%
26/316
|
|
Investigations
Weight increased
|
16.6%
26/157
|
17.1%
54/316
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.0%
22/157
|
17.1%
54/316
|
|
Metabolism and nutrition disorders
Fluid retention
|
1.9%
3/157
|
6.6%
21/316
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.1%
8/157
|
8.9%
28/316
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.1%
8/157
|
10.4%
33/316
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
19.1%
30/157
|
13.6%
43/316
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
30.6%
48/157
|
33.9%
107/316
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.5%
29/157
|
22.5%
71/316
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.8%
17/157
|
12.3%
39/316
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
1.3%
2/157
|
5.1%
16/316
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
43.9%
69/157
|
44.6%
141/316
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.4%
10/157
|
4.4%
14/316
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
14.0%
22/157
|
9.2%
29/316
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
23.6%
37/157
|
26.3%
83/316
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
6.4%
10/157
|
5.1%
16/316
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
21.0%
33/157
|
25.0%
79/316
|
|
Nervous system disorders
Dizziness
|
24.2%
38/157
|
14.9%
47/316
|
|
Nervous system disorders
Dysgeusia
|
5.1%
8/157
|
11.7%
37/316
|
|
Nervous system disorders
Headache
|
29.3%
46/157
|
31.0%
98/316
|
|
Nervous system disorders
Paraesthesia
|
7.0%
11/157
|
5.1%
16/316
|
|
Psychiatric disorders
Anxiety
|
7.6%
12/157
|
7.6%
24/316
|
|
Psychiatric disorders
Depression
|
12.7%
20/157
|
10.1%
32/316
|
|
Psychiatric disorders
Insomnia
|
13.4%
21/157
|
16.8%
53/316
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.7%
34/157
|
23.4%
74/316
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.4%
10/157
|
13.9%
44/316
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.1%
8/157
|
6.6%
21/316
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.3%
13/157
|
8.5%
27/316
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.7%
9/157
|
12.0%
38/316
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.5%
4/157
|
5.7%
18/316
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
11.5%
18/157
|
7.9%
25/316
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.6%
15/157
|
13.0%
41/316
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.4%
32/157
|
37.7%
119/316
|
|
Vascular disorders
Hypertension
|
7.6%
12/157
|
5.7%
18/316
|
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