Trial Outcomes & Findings for Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients (NCT NCT01275196)

Last Updated: 2016-04-08

Results Overview

Major molecular response (MMR) was defined as a value of ≤ 0.1% of BCR-ABL ratio on the IS. The minimum number of control genes for a sample to be valid was 3000. For statistical comparison purpose, MMR was considered as a binary variable with patients achieving MMR grouped as 'responders' and patients not achieving MMR, patients with missing PCR evaluations or patients with atypical transcripts at baseline grouped as 'non-responders'. This endpoint was calculated based on the 12 month analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

267 participants

Primary outcome timeframe

12 months

Results posted on

2016-04-08

Participant Flow

Patients were randomized 1:1 between Nilotinib and Imatinib.

Participant milestones

Participant milestones
Measure	Imatinib Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib Patients received 300 mg bid (600 mg/day)
Overall Study STARTED	133	134
Overall Study Intended to Continue Into Extension	112	113
Overall Study COMPLETED	113	113
Overall Study NOT COMPLETED	20	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Imatinib Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib Patients received 300 mg bid (600 mg/day)
Overall Study Adverse Event	3	5
Overall Study Withdrawal by Subject	4	5
Overall Study Lost to Follow-up	1	0
Overall Study Disease Progression	6	5
Overall Study Protocol Violation	1	0
Overall Study Suboptimal response/treatment failure	5	6

Baseline Characteristics

Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Total n=267 Participants Total of all reporting groups
Age, Continuous	39.7 Years STANDARD_DEVIATION 12.86 • n=5 Participants	41.5 Years STANDARD_DEVIATION 12.76 • n=7 Participants	40.6 Years STANDARD_DEVIATION 12.82 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	43 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	91 Participants n=7 Participants	172 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Patients in the FAS consisted of all patients who were randomized into the study. Following the intent-to-treat principle, patients were analyzed according to the treatment group to which they were assigned at randomization.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Major Molecular Response (MMR) at 12 Months - With Imputation.	27.8 Percentage of Participants Interval 20.4 to 36.3	52.2 Percentage of Participants Interval 43.4 to 60.9	—

SECONDARY outcome

Timeframe: Months 3,6,9,12,15, 18, 21, 24, 36

Major molecular response (MMR) was defined as a value of ≤ 0.1% of BCR-ABL ratio on the IS. The minimum number of control genes for a sample to be valid was 3000. For statistical comparison purpose, MMR was considered as a binary variable with patients achieving MMR grouped as 'responders' and patients not achieving MMR, patients with missing PCR evaluations or patients with atypical transcripts at baseline grouped as 'non-responders'. These time points including the 12 month data were calculated based on the final analysis after the end of the study.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
MMR Rate at Each Time Point 12 Months	27.8 Percentage of Participants Interval 20.4 to 36.3	53.0 Percentage of Participants Interval 44.2 to 61.7	—
MMR Rate at Each Time Point 15 Months	36.1 Percentage of Participants Interval 27.9 to 44.9	59.0 Percentage of Participants Interval 50.1 to 67.4	—
MMR Rate at Each Time Point 36 Months	59.4 Percentage of Participants Interval 50.5 to 67.8	68.7 Percentage of Participants Interval 60.1 to 76.4	—
MMR Rate at Each Time Point 3 Months	3.0 Percentage of Participants Interval 0.8 to 7.5	13.4 Percentage of Participants Interval 8.2 to 20.4	—
MMR Rate at Each Time Point 6 Months	18.0 Percentage of Participants Interval 11.9 to 25.6	44.8 Percentage of Participants Interval 36.2 to 53.6	—
MMR Rate at Each Time Point 9 Months	21.1 Percentage of Participants Interval 14.5 to 29.0	47.8 Percentage of Participants Interval 39.1 to 56.6	—
MMR Rate at Each Time Point 18 Months	40.6 Percentage of Participants Interval 32.2 to 49.5	57.5 Percentage of Participants Interval 48.6 to 66.0	—
MMR Rate at Each Time Point 21 Months	41.4 Percentage of Participants Interval 32.9 to 50.2	61.9 Percentage of Participants Interval 53.2 to 70.2	—
MMR Rate at Each Time Point 24 Months	49.6 Percentage of Participants Interval 40.8 to 58.4	61.9 Percentage of Participants Interval 53.2 to 70.2	—

SECONDARY outcome

Timeframe: Months 3,6,9,12,15, 18, 21, 24, 36

Best MMR rates by scheduled time point are cumulative response rates up to that time point. In this analysis, patients who had achieved MMR at or before the time point were counted as responders, no matter if they lost the response/discontinued or not. Therefore, this response rate represented the best observed response rate up to that specific time point.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Best MMR by Each Timepoint Month 6	18.0 Percentage of Participants Interval 11.9 to 25.6	45.5 Percentage of Participants Interval 36.9 to 54.3	—
Best MMR by Each Timepoint Month 9	22.6 Percentage of Participants Interval 15.8 to 30.6	51.5 Percentage of Participants Interval 42.7 to 60.2	—
Best MMR by Each Timepoint Overall	66.9 Percentage of Participants Interval 58.2 to 74.8	73.9 Percentage of Participants Interval 65.6 to 81.1	—
Best MMR by Each Timepoint Month 3	3.0 Percentage of Participants Interval 0.8 to 7.5	13.4 Percentage of Participants Interval 8.2 to 20.4	—
Best MMR by Each Timepoint Month 12	30.8 Percentage of Participants Interval 23.1 to 39.4	56.0 Percentage of Participants Interval 47.1 to 64.5	—
Best MMR by Each Timepoint Month 15	37.6 Percentage of Participants Interval 29.3 to 46.4	62.7 Percentage of Participants Interval 53.9 to 70.9	—
Best MMR by Each Timepoint Month 18	42.9 Percentage of Participants Interval 34.3 to 51.7	64.2 Percentage of Participants Interval 55.4 to 72.3	—
Best MMR by Each Timepoint Month 21	46.6 Percentage of Participants Interval 37.9 to 55.5	66.4 Percentage of Participants Interval 57.8 to 74.3	—
Best MMR by Each Timepoint Month 24	52.6 Percentage of Participants Interval 43.8 to 61.3	67.9 Percentage of Participants Interval 59.3 to 75.7	—
Best MMR by Each Timepoint Month 36	65.4 Percentage of Participants Interval 56.7 to 73.4	73.9 Percentage of Participants Interval 65.6 to 81.1	—

SECONDARY outcome

Timeframe: End of study (up to 40 months)

Time to first MMR (months) = (date of first MMR or censoring - date of randomization + 1) / 30.4375.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Time to First MMR	21.7 months Interval 16.5 to 25.2	8.1 months Interval 5.6 to 11.1	—

SECONDARY outcome

Timeframe: 24 months

The rate of durable MMR at 24 months, defined as the proportion of patients who have achieved MMR at 12 months, and also maintain continuous MMR until the 24 month time point (1 month = 28 days) without intervening loss of MMR in between 12 and 24 months

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Durable MMR Rate at 24 Months	27.8 Perentage of Participants Interval 20.4 to 36.3	50.7 Perentage of Participants Interval 42.0 to 59.5	—

SECONDARY outcome

Timeframe: End of Study (Up to 40 months)

Duration of first MMR (months) = (date of loss of MMR or censoring-date of first MMR + 1)/30.4375.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Duration of First MMR Among Patients Who Achieved MMR	NA Months The median was not reached.	NA Months The median was not reached.	—

SECONDARY outcome

Timeframe: Months 6, 12, 18, 30, 24, 36

CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Overall	89.5 Percentage of Participants Interval 83.0 to 94.1	85.8 Percentage of Participants Interval 78.7 to 91.2	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 6	57.1 Percentage of Participants Interval 48.3 to 65.7	66.4 Percentage of Participants Interval 57.8 to 74.3	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 12	80.5 Percentage of Participants Interval 72.7 to 86.8	77.6 Percentage of Participants Interval 69.6 to 84.4	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 18	84.2 Percentage of Participants Interval 76.9 to 90.0	80.6 Percentage of Participants Interval 72.9 to 86.9	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 30	88.0 Percentage of Participants Interval 81.2 to 93.0	84.3 Percentage of Participants Interval 77.0 to 90.0	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 24	86.5 Percentage of Participants Interval 79.5 to 91.8	83.6 Percentage of Participants Interval 76.2 to 89.4	—
Best Complete Cytogenic Response (CCyR) Rate by Each Time Point Month 36	89.5 Percentage of Participants Interval 83.0 to 94.1	85.8 Percentage of Participants Interval 78.7 to 91.2	—

SECONDARY outcome

Timeframe: End of study (up to 40 months)

Time to first CCyR (months) = (date of first CCyR - date of randomization + 1) / 30.4375.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Time to First CCYR	6.1 months Interval 5.6 to 6.6	5.6 months Interval 5.6 to 6.2	—

SECONDARY outcome

Timeframe: End of Study (up to 40 months)

Duration of CCyR (months) = (date of CCyR loss or censoring-date of first CCyR + 1)/30.4375

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Duration of First CCyR Among Patients Who Achieved CCyR	NA Months The median was not reached.	NA Months The median was not reached.	—

SECONDARY outcome

Timeframe: End of study (up to 40 months)

Time to progression to AP/BC was defined as the time from the date of randomization to the date of event defined as the first disease progression to AP/BC or the date of CML-related death, whichever is earlier. This variable was analyzed in 2 ways: * On-treatment: included progressions to AP/BC or CML-related deaths occurring on treatment in the study as events. The time was censored at the date of last on-treatment assessment (hematology, extramedullary disease, or cytogenetic evaluation) in the study for patients without event. * On-study: included progressions to AP/BC or CML-related deaths occurring in the study or during the follow-up period after discontinuation of treatment as events. The time was censored at the last assessment date in the study for patients who were still being treated and at the date of last contact for patients who discontinued treatment

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Time to Progression to Accelerated Phase/Blast Crisis (AP/BC) on Treatment	NA Months The median was not reached.	NA Months The median was not reached.	—

SECONDARY outcome

Timeframe: End of Study (up to 40 months)

Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following:-Death due to any cause, - Progression to AP or BC, Loss of partial cytogenetic response (PCyR), - Loss of CCyR, - Loss of CHR

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Event-free Survival (EFS) on Treatment	NA Months The median was not reached.	NA Months The median was not reached.	—

SECONDARY outcome

Timeframe: End of study (up to 40 months)

Progression-free survival was defined as the time from the date of randomization to the date of event defined as the first disease progression to AP/BC or the date of death from any cause, whichever is earlier. This variable was analyzed in 2 ways: * On-treatment: included progressions to AP/BC or deaths occurring only on-treatment in the study as events. The time was censored at the date of last on-treatment assessment (hematology, extramedullary disease or cytogenetic evaluation) in the study before the cut-off date of the analysis for patients without event. * On-study: included progressions to AP/BC or deaths occurring in the study or during the follow-up period after discontinuation of study treatment as events. The time was censored at the last assessment date in the study for patients who were still being treated and at the date of last contact for patients who discontinued treatment.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Progression-free Survival (PFS) on Treatment	NA Months The median was not reached.	NA Months The median was not reached.	—

SECONDARY outcome

Timeframe: End of Study (up to 40 months)

Patients who discontinued study treatment early or completed the study protocol and did not enter into the extension protocol were to be followed for survival every 3 months for up to 2 calendar years from the date the last patient randomized received the first dose of study drug and every 6 months until Last Patient Last Visit. Overall survival (all deaths) was defined as the time between date of randomization and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment, i.e. overall survival on-study. The time was censored at the date of last assessment in the study for patients who are still being treated and at the date of last contact for patients who discontinued treatment.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Kaplan-Meier Estimates of Overall Survival (OS) on Treatment	NA Months Median could not be reached.	NA Months Median could not be reached.	—

SECONDARY outcome

Timeframe: Months 1, 3, 4, 5, 6, 9,12, 15,18, 21, 24, 30, 36

CHR was defined as having all of the following criteria present at any assessment, which was confirmed by another assessment at least after 4 weeks: • WBC count \< 10 x 10E9 /L • Platelet count \< 450 x 10E9 /L • Basophils \< 5% • No blasts and promyelocytes in peripheral blood • Myelocytes + metamyelocytes \< 5 % in peripheral blood • No evidence of extramedullary involvement. The assessment was not considered CHR, if there were any values indicative of CML in AP or BC (i.e. by blasts in bone marrow). For confirmation of CHR, both the initial CHR as well as the confirming assessment (at least 4 weeks after the initial assessment) had to satisfy all criteria mentioned above, without any assessment in between which indicated 'No response'.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Best Complete Hematologic Response (CHR) Month 5	94.0 Percentage of participants Interval 88.5 to 97.4	93.3 Percentage of participants Interval 87.6 to 96.9	—
Best Complete Hematologic Response (CHR) Month 18	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—
Best Complete Hematologic Response (CHR) Month 21	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—
Best Complete Hematologic Response (CHR) Overall	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—
Best Complete Hematologic Response (CHR) Month 1	66.2 Percentage of participants Interval 57.5 to 74.1	73.1 Percentage of participants Interval 64.8 to 80.4	—
Best Complete Hematologic Response (CHR) Month 3	91.0 Percentage of participants Interval 84.8 to 95.3	91.8 Percentage of participants Interval 85.8 to 95.8	—
Best Complete Hematologic Response (CHR) Month 4	93.2 Percentage of participants Interval 87.5 to 96.9	93.3 Percentage of participants Interval 87.6 to 96.9	—
Best Complete Hematologic Response (CHR) Month 6	94.7 Percentage of participants Interval 89.5 to 97.9	93.3 Percentage of participants Interval 87.6 to 96.9	—
Best Complete Hematologic Response (CHR) Month 9	94.7 Percentage of participants Interval 89.5 to 97.9	93.3 Percentage of participants Interval 87.6 to 96.9	—
Best Complete Hematologic Response (CHR) Month 12	94.7 Percentage of participants Interval 89.5 to 97.9	94.0 Percentage of participants Interval 88.6 to 97.4	—
Best Complete Hematologic Response (CHR) Month 15	94.7 Percentage of participants Interval 89.5 to 97.9	94.0 Percentage of participants Interval 88.6 to 97.4	—
Best Complete Hematologic Response (CHR) Month 24	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—
Best Complete Hematologic Response (CHR) Month 30	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—
Best Complete Hematologic Response (CHR) Month 36	94.7 Percentage of participants Interval 89.5 to 97.9	94.8 Percentage of participants Interval 89.5 to 97.9	—

SECONDARY outcome

Timeframe: End of Study (up to 40 months)

Patients satisfying criteria for several "modified ELN 2009" categories are presented once under the worst category (Optimal\> Suboptimal \> Treatment failure). Patients in the "Discontinued" category are those who discontinued before the time point considered without satisfying any of the ELN 2009 criteria. Patients in the "Missing" category are those ongoing in the trial at the time point considered but with only missing or non evaluable data for ELN 2009 criteria.

Outcome measures

Outcome measures
Measure	Imatinib n=133 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=134 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Modified ELN2009 Criteria Optimal Response	39.8 Percentage of Participants	55.2 Percentage of Participants	—
Modified ELN2009 Criteria Treatment Failure	16.5 Percentage of Participants	14.9 Percentage of Participants	—
Modified ELN2009 Criteria Suboptimal Response	41.4 Percentage of Participants	24.6 Percentage of Participants	—
Modified ELN2009 Criteria Discontinued	2.3 Percentage of Participants	5.2 Percentage of Participants	—

SECONDARY outcome

Timeframe: End of Study (up to 40 months)

Population: Safety set consisted of all randomized patients who received at least one dose of study medication.

Total dose/time on treatment (periods of zero dose were included).

Outcome measures

Outcome measures
Measure	Imatinib n=132 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=133 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib Patients received 300 mg bid (600 mg/day)
Actual Dose Intensity	416.0 mg/day Standard Deviation 62.40	536.4 mg/day Standard Deviation 99.07	—

SECONDARY outcome

Timeframe: 12 Months

Population: Pharmacokinetic Analysis Set

Pharmacokinetic Analysis Set

Outcome measures

Outcome measures
Measure	Imatinib n=93 Participants Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib n=93 Participants Patients received 300 mg bid (600 mg/day)	Nilotinib n=130 Participants Patients received 300 mg bid (600 mg/day)
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Day 8 (Cycle 1)	1235.3 ng/mL Standard Deviation 632.36	255.4 ng/mL Standard Deviation 154.74	1036.8 ng/mL Standard Deviation 618.10
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Day 28 (Cycle 1)	1291.3 ng/mL Standard Deviation 553.44	288.9 ng/mL Standard Deviation 130.25	970.4 ng/mL Standard Deviation 606.89
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Day 84 (Cycle 3)	1137.8 ng/mL Standard Deviation 461.50	235.7 ng/mL Standard Deviation 104.31	1172.4 ng/mL Standard Deviation 656.25
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Day 168 (Cycle 6)	1078.2 ng/mL Standard Deviation 413.99	243.2 ng/mL Standard Deviation 88.66	1154.8 ng/mL Standard Deviation 1034.15
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Day 336 (Cycle 12)	1111.1 ng/mL Standard Deviation 434.85	238.7 ng/mL Standard Deviation 89.11	1370.5 ng/mL Standard Deviation 878.88
Summary Statistics of Trough Imatinib and Major Metabolite CGP74588 of Imatinib and Nilotinib PK Concentration by Time Point Average trough PK	1188.7 ng/mL Standard Deviation 452.24	258.7 ng/mL Standard Deviation 112.88	1137.4 ng/mL Standard Deviation 631.31

Adverse Events

Imatinib 400 mg qd

Serious events: 13 serious events

Other events: 124 other events

Deaths: 0 deaths

Nilotinib 300 mg Bid

Serious events: 11 serious events

Other events: 131 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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 or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	Imatinib 400 mg qd n=132 participants at risk Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib 300 mg Bid n=133 participants at risk Patients received 300 mg bid (600 mg/day)
Reproductive system and breast disorders Ovarian rupture	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Bone marrow failure	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	2.3% 3/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Granulocytopenia	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Thrombocytopenia	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Thrombocytopenic purpura	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Thrombocytosis	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Eye disorders Diabetic retinopathy	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Gastrointestinal disorders Abdominal pain	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Infections and infestations Anal abscess	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Infections and infestations Upper respiratory tract infection bacterial	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Injury, poisoning and procedural complications Ankle fracture	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Blast cell count increased	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Neutrophil count decreased	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Platelet count decreased	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	2.3% 3/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations White blood cell count decreased	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage 0	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma recurrent	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal squamous cell carcinoma	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Nervous system disorders Cerebral haemorrhage	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Renal and urinary disorders Urinary retention	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Reproductive system and breast disorders Prostatic obstruction	0.00% 0/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.75% 1/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.76% 1/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.

Measure	Imatinib 400 mg qd n=132 participants at risk Patients received 400 mg qd (400 mg/day; may be increased to 600 mg/day).	Nilotinib 300 mg Bid n=133 participants at risk Patients received 300 mg bid (600 mg/day)
Blood and lymphatic system disorders Anaemia	13.6% 18/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.0% 12/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Leukopenia	26.5% 35/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	20.3% 27/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Neutropenia	13.6% 18/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	5.3% 7/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Blood and lymphatic system disorders Thrombocytopenia	28.0% 37/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	30.8% 41/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Eye disorders Eyelid oedema	18.9% 25/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.0% 4/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Gastrointestinal disorders Abdominal pain upper	2.3% 3/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	6.0% 8/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Gastrointestinal disorders Diarrhoea	13.6% 18/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.8% 5/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Gastrointestinal disorders Nausea	10.6% 14/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.8% 5/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Gastrointestinal disorders Vomiting	10.6% 14/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	2.3% 3/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
General disorders Face oedema	8.3% 11/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	0.00% 0/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
General disorders Pyrexia	11.4% 15/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.0% 12/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Hepatobiliary disorders Hyperbilirubinaemia	3.0% 4/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	30.1% 40/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Infections and infestations Influenza	5.3% 7/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.8% 5/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Infections and infestations Nasopharyngitis	18.9% 25/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	12.8% 17/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Infections and infestations Upper respiratory tract infection	9.8% 13/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	7.5% 10/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Alanine aminotransferase increased	12.1% 16/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	21.1% 28/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Apolipoprotein B increased	2.3% 3/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	6.8% 9/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Aspartate aminotransferase increased	6.8% 9/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.8% 13/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Bilirubin conjugated increased	2.3% 3/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	11.3% 15/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Blood bilirubin increased	6.1% 8/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	30.8% 41/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Blood creatine phosphokinase increased	9.1% 12/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	4.5% 6/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Blood phosphorus decreased	7.6% 10/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	7.5% 10/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Gamma-glutamyltransferase increased	2.3% 3/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	11.3% 15/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Haemoglobin decreased	10.6% 14/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	6.0% 8/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Lipase increased	22.0% 29/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	27.8% 37/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Low density lipoprotein increased	2.3% 3/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	8.3% 11/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Neutrophil count decreased	12.1% 16/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	11.3% 15/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations Platelet count decreased	22.7% 30/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	17.3% 23/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Investigations White blood cell count decreased	21.2% 28/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	12.0% 16/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Hypercholesterolaemia	1.5% 2/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.0% 12/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Hyperglycaemia	3.8% 5/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	7.5% 10/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Hypertriglyceridaemia	7.6% 10/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.0% 12/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Hypokalaemia	9.8% 13/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.0% 4/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Metabolism and nutrition disorders Hypophosphataemia	12.9% 17/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	11.3% 15/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 9/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	1.5% 2/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Musculoskeletal and connective tissue disorders Myalgia	6.1% 8/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	12.0% 16/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Nervous system disorders Dizziness	6.1% 8/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	1.5% 2/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Nervous system disorders Headache	3.0% 4/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	9.0% 12/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Respiratory, thoracic and mediastinal disorders Cough	6.8% 9/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	3.0% 4/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.
Skin and subcutaneous tissue disorders Rash	12.9% 17/132 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.	35.3% 47/133 The safety set consisted of all patients who received at least one dose of study medication. Two patients (1 in each arm) who were randomized but never treated were excluded from the safety set.