Trial Outcomes & Findings for Study of Bosutinib in Japanese Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (NCT NCT03128411)

NCT ID: NCT03128411

Last Updated: 2022-05-19

Results Overview

A MMR is defined as less than or equal to (\<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a \>=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. The MMR value counted only if the response was demonstrated at the 12-month visit; any MMR gained and lost, or never achieved at or before the 12-month visit was considered as non-responder.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: Month 12
• Results posted on: 2022-05-19

Participant Flow

Participant milestones

Measure	Bosutinib Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Treatment Phase STARTED	60
Treatment Phase Received Treatment	60
Treatment Phase COMPLETED	36
Treatment Phase NOT COMPLETED	24
Long Term Follow-up Phase STARTED	24
Long Term Follow-up Phase COMPLETED	22
Long Term Follow-up Phase NOT COMPLETED	2

Reasons for withdrawal

Measure	Bosutinib Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Treatment Phase Adverse Event	21
Treatment Phase Physician Decision	1
Treatment Phase Other	2
Long Term Follow-up Phase Death	2

Baseline Characteristics

Study of Bosutinib in Japanese Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

Baseline characteristics by cohort

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Age, Continuous	53.3 years STANDARD_DEVIATION 16.40 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	60 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

A MMR is defined as less than or equal to (<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. The MMR value counted only if the response was demonstrated at the 12-month visit; any MMR gained and lost, or never achieved at or before the 12-month visit was considered as non-responder.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Major Molecular Response (MMR) at Month 12

55.0 Percentage of participants Interval 44.4 to 65.6

SECONDARY outcome

Timeframe: Up to Month 12

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

A MMR is defined as less than or equal to (<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. The MMR value counted only if the response was demonstrated at or before the 12-month visit.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Major Molecular Response (MMR) by Month 12

61.7 Percentage of participants Interval 51.3 to 72.0

SECONDARY outcome

Timeframe: Up to Month 18

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

A MMR is defined as less than or equal to (<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. The MMR value counted only if the response was demonstrated at or before the 18-month visit.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Major Molecular Response (MMR) by Month 18

66.7 Percentage of participants Interval 56.7 to 76.7

SECONDARY outcome

Timeframe: Up to Month 12

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

CCyR is based on the prevalence of Philadelphia chromosome positive metaphases among cells in metaphase on a bone marrow sample. CCyR was defined as absence of detectable Philadelphia chromosome positive cells. CCyR was achieved when there were "0" Philadelphia chromosome positive metaphases among at least 20 metaphases from a bone marrow sample or when MMR was achieved if no bone marrow analysis was performed. The CCyR value was counted only if the response was demonstrated at or before the 12-month visit.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Complete Cytogenetic Response (CCyR) by Month 12

80.0 Percentage of participants Interval 71.5 to 88.5

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment. Here, ''Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure and who had MMR.

Duration of MMR: time from first date of MMR until first date of confirmed loss of MMR, treatment discontinuation due to progressive disease (PD), or death due to PD within 28 days after last dose or censoring. PD: progression to Accelerated phase (AP) or to Blast Phase (BP). AP: 15-29% blasts in blood or marrow, or>30% blasts plus promyelocytes in blood or marrow with blasts <30%; ≥20% basophils in blood. BP: ≥30% Blasts in blood or bone marrow, extramedullary blast proliferation, other than in spleen. Kaplan-Meier analysis was used.

Outcome measures

Measure

Bosutinib n=42 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Probability of Maintaining Major Molecular Response (MMR) at Month 36

100.0 Percentage of participants Interval 100.0 to 100.0

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment. Here, ''Overall Number of Participants Analyzed'' signifies number of participants evaluable for this outcome measure and who had CCyR.

Duration of CCyR, from first date of CCyR to confirmed loss of CCyR, treatment discontinuation due to PD, death due to PD within 28 days after last dose or censoring. Confirmed loss: at least 1 Ph+ metaphase confirmed by a second determination >=4 weeks later or unconfirmed loss followed by treatment discontinuation due to suboptimal response. PD: progression to AP or to BP. Kaplan-Meier analysis was used.

Outcome measures

Measure

Bosutinib n=48 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Probability of Maintaining Complete Cytogenetic Response (CCyR) at Month 36

100.0 Percentage of participants Interval 100.0 to 100.0

SECONDARY outcome

Timeframe: Up to Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

EFS: time from 1st dose until 1st occurrence of 1 of the following events or censoring: 1)death from any cause 2)transformation to AP or BP 3)loss of complete hematologic response (CHR) 4)loss of CCyR 5)participants not achieving CHR: doubling of WBCs >= 1 month apart with 2nd value >20*10^9/L and maintained in subsequent assessments for >=2 weeks. Loss of CHR: appearance of any of the following confirmed by 2nd determination>=4 weeks later (unless associated with CML-related treatment discontinuation): WBC count: >20.0*10^9/L, platelet count: >=600*10^9/L, appearance of palpable spleen/other extra medullary involvement, appearance of 5% myelocytes or blasts or promyelocytes in peripheral blood. Loss of CCyR:>= one Ph+ metaphase confirmed by 2nd determination >=4 weeks later(unless associated with CML-related treatment discontinuation). Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Event Free Survival (EFS) at Month 36

1.7 Percentage of participants Interval 0.2 to 6.4

SECONDARY outcome

Timeframe: Up to Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Overall survival was defined as the time from first dose of study drug to death due to any cause or censoring. Kaplan-Meier analysis was used for determination of probability of overall survival.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Probability of Overall Survival (OS) at Month 36

96.7 Percentage of participants Interval 89.7 to 98.9

SECONDARY outcome

Timeframe: Pre-dose on Day 1, Day 28, Day 56, Day 84

Population: The PK population will be defined as any patient in the safety population of patients who had at least 1 concentration of bosutinib on-treatment.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Trough Plasma Concentrations of Bosutinib Day 1	0.000 Nanogram per milliliter (ng/mL) Standard Deviation 0.000
Trough Plasma Concentrations of Bosutinib Day 28	83.564 Nanogram per milliliter (ng/mL) Standard Deviation 64.1056
Trough Plasma Concentrations of Bosutinib Day 56	85.963 Nanogram per milliliter (ng/mL) Standard Deviation 46.4095
Trough Plasma Concentrations of Bosutinib Day 84	79.659 Nanogram per milliliter (ng/mL) Standard Deviation 41.5369

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of participants with MMR response as "Yes" and "No" at specified time points. A MMR is defined as less than or equal to (<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response Yes: Day 28	94.943 ng/mL Standard Deviation 71.9332
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response No: Day 28	59.770 ng/mL Standard Deviation 35.4568
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response Yes: Day 56	88.196 ng/mL Standard Deviation 48.9671
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response No: Day 56	82.092 ng/mL Standard Deviation 42.9741
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response Yes: Day 84	81.339 ng/mL Standard Deviation 41.5443
Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response No: Day 84	75.654 ng/mL Standard Deviation 42.9290

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of participants with CCyR Response as "Yes" and "No" at specified time points. CCyR is based on the prevalence of Philadelphia chromosome positive metaphases among cells in metaphase on a bone marrow sample. CCyR was defined as absence of detectable Philadelphia chromosome positive cells. CCyR was achieved when there were "0" Philadelphia chromosome positive metaphases among at least 20 metaphases from a bone marrow sample or when MMR was achieved if no bone marrow analysis was performed.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response Yes: Day 28	87.006 ng/mL Standard Deviation 64.1820
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response No: Day 28	28.490 ng/mL Standard Deviation 38.3393
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response Yes: Day 56	90.550 ng/mL Standard Deviation 45.4543
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response No: Day 56	52.936 ng/mL Standard Deviation 43.6721
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response Yes: Day 84	79.429 ng/mL Standard Deviation 40.1538
Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response No: Day 84	82.800 ng/mL Standard Deviation 69.5117

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against each categories/levels respectively.

Trough bosutinib plasma concentration is reported classified on basis of total bilirubin level range at baseline. Level range 1: <=7.7 micromole per liter (micromol/L), level rage 2: >7.7 and <= 10.3 micromol/L, level range 3: >10.3 and <=12.85 micromol/L and level range 4: >12.85 micromol/L.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 84: (>7.7 and <=10.3 micromol/L)	75.478 ng/mL Standard Deviation 34.0806
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 84: (>10.3 and <=12.85 micromol/L)	98.133 ng/mL Standard Deviation 56.5691
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 84: (>12.85 micromol/L)	95.950 ng/mL Standard Deviation 46.2820
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 28: (<=7.7 micromol/L)	61.833 ng/mL Standard Deviation 18.0632
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 28: (>7.7 and <=10.3 micromol/L)	96.867 ng/mL Standard Deviation 87.7756
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 28: (>10.3 and <=12.85 micromol/L)	76.963 ng/mL Standard Deviation 59.0962
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 28: (>12.85 micromol/L)	84.599 ng/mL Standard Deviation 54.3057
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 56: (<=7.7 micromol/L)	60.044 ng/mL Standard Deviation 22.6753
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 56: (>7.7 and <=10.3 micromol/L)	81.246 ng/mL Standard Deviation 44.3985
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 56: (>10.3 and <=12.85 micromol/L)	91.940 ng/mL Standard Deviation 49.9495
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 56: (>12.85 micromol/L)	107.025 ng/mL Standard Deviation 53.5192
Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin Day 84: (<=7.7 micromol/L)	50.775 ng/mL Standard Deviation 19.4910

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against each categories/levels respectively.

Trough bosutinib plasma concentration is reported classified on basis of different ranges of creatinine clearance at baseline. Level range 1: <=71.479 milliliter per minute (mL/min), level rage 2: >71.479 and <=100.936 mL/min, level range 3: >100.936 and <=129.355 mL/min) and level range 4: >129.355 mL/min.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 84:(>100.936 and <=1 29.355 mL/min)	69.100 ng/mL Standard Deviation 41.0767
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 84: (>129.355 mL/min)	70.277 ng/mL Standard Deviation 30.6643
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 28: (<=71.479 mL/min)	75.039 ng/mL Standard Deviation 63.7599
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 28: (>71.479 and <=10 0.936 mL/min)	84.114 ng/mL Standard Deviation 49.0390
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 28: (>100.936 and <=1 29.355 mL/min)	100.100 ng/mL Standard Deviation 97.8388
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 28: (>129.355 mL/min)	72.610 ng/mL Standard Deviation 26.2392
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 56:(<=71.479 mL/min)	93.056 ng/mL Standard Deviation 56.2220
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 56:(>71.479 and <=10 0.936 mL/min)	92.764 ng/mL Standard Deviation 47.9905
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 56: (>100.936 and <=1 29.355 mL/min)	95.580 ng/mL Standard Deviation 58.4145
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 56: (>129.355 mL/min)	72.200 ng/mL Standard Deviation 32.9961
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 84: (<=71.479 mL/min)	92.540 ng/mL Standard Deviation 49.2182
Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance Day 84:(>71.479 and <=10 0.936 mL/min)	90.590 ng/mL Standard Deviation 45.9533

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against each categories/levels respectively.

Trough bosutinib plasma concentration is reported classified on basis of different ranges of aspartate aminotransferase at baseline. Level range 1: <=22 units per liter (U/L), level rage 2: >22 and <=26 U/L, level range 3: >26 and <=33 U/L and level range 4: >33 U/L.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 28: (<=22 U/L)	65.771 ng/mL Standard Deviation 26.3239
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 28: (>22 and <=26 U/L)	140.617 ng/mL Standard Deviation 120.1651
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 28: (>26 and <=33 U/L)	66.056 ng/mL Standard Deviation 37.4551
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 28: (>33 U/L)	82.711 ng/mL Standard Deviation 47.9527
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 56: (<=22 U/L)	82.117 ng/mL Standard Deviation 51.0937
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 56: (>22 and <=26 U/L)	76.050 ng/mL Standard Deviation 43.6907
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 56: (>26 and <=33 U/L)	93.607 ng/mL Standard Deviation 44.5087
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 56: (>33 U/L)	89.711 ng/mL Standard Deviation 50.6123
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 84: (<=22 U/L)	54.550 ng/mL Standard Deviation 23.4932
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 84: (>22 and <=26 U/L)	81.325 ng/mL Standard Deviation 55.3891
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 84: (>26 and <=33 U/L)	85.886 ng/mL Standard Deviation 39.3348
Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase Day 84: (>33 U/L)	92.208 ng/mL Standard Deviation 41.4203

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against each categories/levels respectively.

Trough bosutinib plasma concentration is reported classified on basis of different ranges of alanine aminotransferase at baseline. Level range 1: <=17.5 U/L, level rage 2: >17.5 and <=25 U/L, level range 3: >25 and <=32 U/L and level range 4: >32 U/L.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 84: (>25 and <=32 U/L)	92.254 ng/mL Standard Deviation 49.1564
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 84: (>32 U/L)	81.462 ng/mL Standard Deviation 29.7583
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 28: (<=17.5 U/L)	49.111 ng/mL Standard Deviation 24.6077
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 28: (>17.5 and <=25 U/L)	98.882 ng/mL Standard Deviation 131.3382
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 28: (>25 and <=32 U/L)	94.175 ng/mL Standard Deviation 44.7227
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 28: (>32 U/L)	86.000 ng/mL Standard Deviation 39.7021
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 56: (<=17.5 U/L)	66.878 ng/mL Standard Deviation 33.4154
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 56: (>17.5 and <=25 U/L)	82.317 ng/mL Standard Deviation 69.6971
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 56: (>25 and <= 32 U/L)	104.350 ng/mL Standard Deviation 47.3634
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 56: (>32 U/L)	85.354 ng/mL Standard Deviation 40.1619
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 84: (<=17.5 U/L)	65.011 ng/mL Standard Deviation 43.4694
Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase Day 84: (>17.5 and <=25 U/L)	73.511 ng/mL Standard Deviation 43.4070

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of presence/ or absence of grade 1 diarrhea as "Yes" and "No" at specified time points. As per national cancer institute common terminology criteria (NCI-CTCAE) version 4.03, Grade 1: increase of <4 stools per day over baseline.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea Yes: Day 28	85.585 ng/mL Standard Deviation 69.4219
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea No: Day 28	74.133 ng/mL Standard Deviation 31.1208
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea Yes: Day 56	86.086 ng/mL Standard Deviation 46.9140
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea No: Day 56	85.080 ng/mL Standard Deviation 47.7414
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea Yes: Day 84	85.219 ng/mL Standard Deviation 41.7195
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea No: Day 84	50.271 ng/mL Standard Deviation 26.8976

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of presence/ or absence of grade 1 Nausea as "Yes" and "No" at specified time points. As per NCI-CTCAE version 4.03, Grade 1: loss of appetite without alteration in eating habits.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea Yes: Day 28	90.998 ng/mL Standard Deviation 72.5190
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea No: Day 28	81.971 ng/mL Standard Deviation 63.5134
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea Yes: Day 56	111.482 ng/mL Standard Deviation 54.9565
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea No: Day 56	76.606 ng/mL Standard Deviation 39.8971
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea Yes: Day 84	91.867 ng/mL Standard Deviation 57.5206
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea No: Day 84	76.520 ng/mL Standard Deviation 36.7957

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of presence/ or absence of grade 1 vomiting as "Yes" and "No" at specified time points. As per NCI-CTCAE version 4.03, Grade 1: 1 - 2 episodes (separated by 5 minutes) in 24 hours.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting Yes: Day 28	58.826 ng/mL Standard Deviation 29.1613
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting No: Day 28	89.977 ng/mL Standard Deviation 69.3702
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting Yes: Day 56	87.135 ng/mL Standard Deviation 53.5627
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting No: Day 56	85.533 ng/mL Standard Deviation 44.5062
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting Yes: Day 84	90.030 ng/mL Standard Deviation 32.1444
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting No: Day 84	76.609 ng/mL Standard Deviation 43.8653

SECONDARY outcome

Timeframe: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest

Population: PK population included of all enrolled participants, who received at least 1 dose of study treatment and had at least 1 concentration of bosutinib on-treatment. For Day 28, 56, 84: total number of participants analyzed for each time point were sum of "number analyzed" against Yes and No categories respectively.

Trough bosutinib plasma concentration is reported classified on basis of presence/ or absence of grade 1 thrombocytopenia as "Yes" and "No" at specified time points. As per NCI-CTCAE version 4.03, Grade 1: platelet count decreased: 75.0 - 50.0*10^9/L.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia Yes: Day 28	80.167 ng/mL Standard Deviation 46.6352
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia No: Day 28	83.893 ng/mL Standard Deviation 66.1379
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia Yes: Day 56	87.700 ng/mL Standard Deviation 35.9669
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia No: Day 56	85.722 ng/mL Standard Deviation 48.0957
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia Yes: Day 84	75.067 ng/mL Standard Deviation 33.1815
Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia No: Day 84	79.995 ng/mL Standard Deviation 42.4024

SECONDARY outcome

Timeframe: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The severity was graded by NCI CTCAE v.4.03. Grade 1 was mild AE. Grade 2 was moderate AE. Grade 3 was severe AE. Grade 4 was life-threatening consequences and urgent intervention indicated AE. Grade 5 was death related to AE. Number of participants with Grade 3 or higher AEs are reported.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Number of Participants With Treatment-Emergent Adverse Events (AEs): National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or Higher

49 Participants

SECONDARY outcome

Timeframe: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

Laboratory parameters include: Alanine aminotransferase (ALT) increased: Grade 3: >5.0-20.0*upper limit of normal (ULN),Grade 4:>20.0*ULN, Alkaline phosphatase (ALP) increased: Grade 3: >5.0 - 20.0 x ULN, Grade 4: >20.0 x ULN, Aspartate aminotransferase (AST) increased: Grade 3: >5.0 - 20.0 *ULN, Grade 4: >20.0*ULN. Blood bilirubin increased:Grade 3:>3.0 - 10.0*ULN,Grade 4: >10.0*ULN, creatine phosphokinase (CPK) increased: Grade 3: >5*ULN-10*ULN, Grade 4: >10*ULN, Hyperglycemia: Grade 3: >250-500 milligrams/deciliter (mg/dL), Grade 4: >500 mg/dL. Hypermagnesemia: Grade 3: >3.0-8.0 mg/dL, Grade 4: >8.0 mg/dL, Hypokalemia: Grade 3: <3.0-2.5 millimoles/ liter (mmol/L), Grade 4:<2.5 mmol/L); Hyponatremia: Grade 3: <130-120 mmol/L, Grade 4: <120 mmol/L. Hypophosphatemia: Grade 3: <2.0-1.0 mg/dL, Grade 4: <1.0 mg/dL. Lipase increased: Grade 3:>2.0-5.0*ULN, Grade 4: >5.0*ULN. Serum amylase increased: Grade 3: >2.0 - 5.0*ULN, Grade 4: >5.0* ULN.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 ALT increased	30 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 ALP increased	1 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 AST increased	16 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Blood bilirubin increased	1 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 CPK increased	3 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hyperglycemia	2 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypermagnesemia	1 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypokalemia	2 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hyponatremia	3 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypophosphatemia	3 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Lipase increased	14 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Serum amylase increased	1 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Creatinine increased	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypercalcemia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hyperkalemia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypernatremia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypoalbuminemia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypocalcemia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypoglycemia	0 Participants
Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Hypomagnesemia	0 Participants

SECONDARY outcome

Timeframe: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

Laboratory parameters include: Anemia: Grade 3: hemoglobin (Hgb) <8.0 g/dL, Grade 4: Life-threatening consequences; urgent intervention indicated, Lymphocyte count decreased: Grade 3: <500 - 200/millimeter(mm)^3, Grade 4: <200/mm^3, Neutrophil count decreased: Grade 3: <1000 - 500/mm^3, Grade 4: <500/mm^3, Platelet count decreased: Grade 3: <50.0 - 25.0*10^9 /L, Grade 4: <25.0*10^9 /L. White blood cell decreased: Grade 3: <2.0 - 1.0*10^9 /L, Grade 4: <1.0*10^9 /L. Only those rows in which at least 1 participant had data were reported.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Anemia	4 Participants
Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Lymphocyte count decreased	14 Participants
Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Neutrophil count decreased	9 Participants
Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 Platelet count decreased	6 Participants
Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 White blood cell decreased	2 Participants

SECONDARY outcome

Timeframe: From first dose and up to 12 March 2019; maximum of 22 months, approximately

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

Coagulation parameters include: APTT prolonged (Grade 3: >2.5*ULN and hemorrhage), and INR increased (Grade 3 >2.5*ULN).

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants With Laboratory Abnormalities, Coagulation: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 Activated partial thromboplastin time	0 Participants
Number of Participants With Laboratory Abnormalities, Coagulation: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 INR increased	0 Participants

SECONDARY outcome

Timeframe: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

Vital signs included: body weight Increase >= 10% change from baseline and Decrease >= 10% change from baseline, systolic blood pressure in millimeters of mercury (mmHg): <80 mmHg and >210 mmHg, diastolic blood pressure in mmHg: <40 mmHg and >130 mmHg, heart rate in beats per minute (bpm): <40 bpm and >150 bpm, temperature in degree Celsius (C): <32 and >40 degree C.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants With Clinically Significant Vital Signs Findings Body weight: Increase >= 10% change from baseline	12 Participants
Number of Participants With Clinically Significant Vital Signs Findings Body weight: Decrease >= 10% change from baseline	2 Participants
Number of Participants With Clinically Significant Vital Signs Findings Systolic blood pressure: <80 mmHg	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Systolic blood pressure: >210 mmHg	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Diastolic blood pressure: <40 mmHg	1 Participants
Number of Participants With Clinically Significant Vital Signs Findings Diastolic blood pressure: >130 mmHg	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Heart rate: <40 bpm	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Heart rate: >150 bpm	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Temperature: <32 C	0 Participants
Number of Participants With Clinically Significant Vital Signs Findings Temperature: >40 C	1 Participants

SECONDARY outcome

Timeframe: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment.

ECG parameters included: QTc corrected by Bazett's (QTcB) interval: >500 msec (milliseconds), QTc corrected by Fridericia's (QTcF) interval: >500 msec and >450 msec (men) or >470 msec (women).

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings QTcB interval: >500 msec	0 Participants
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings QTcF interval: >500 msec	0 Participants
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings QTcF interval: >450 msec (Men) or >470 msec (Women)	1 Participants

SECONDARY outcome

Timeframe: At end of treatment for patients who discontinued treatment post initial dose (up to 12 March 2019)

Population: As-treated population included all enrolled participants who received at least 1 dose of study treatment. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Interpretation categories included: a) normal, b) abnormal, not clinically significant and c) abnormal, clinically significant.

Outcome measures

Measure	Bosutinib n=18 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Number of Participants Assessed for Left Ventricular Ejection Fraction Normal	15 Participants
Number of Participants Assessed for Left Ventricular Ejection Fraction Abnormal, not clinically significant	3 Participants
Number of Participants Assessed for Left Ventricular Ejection Fraction Abnormal, Clinically Significant	0 Participants

SECONDARY outcome

Timeframe: Month 3, 6, 9 and 18

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

A MMR is defined as less than or equal to (<=) 0.1 percent (%) BCR-ABL transcripts on the international scale (IS), corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. The MMR value counted only if the response was demonstrated at the designated visit; any MMR gained and lost, or never achieved at or before the designated visit was considered as non-responder.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18 Month 3	10.0 Percentage of participants Interval 3.6 to 16.4
Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18 Month 6	50.0 Percentage of participants Interval 39.4 to 60.6
Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18 Month 9	53.3 Percentage of participants Interval 42.7 to 63.9
Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18 Month 18	61.7 Percentage of participants Interval 51.3 to 72.0

SECONDARY outcome

Timeframe: Month 3

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

MR1 is defined as <= 10% BCR-ABL with a minimum of 3,000 ABL transcripts assessed by the central laboratory.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Molecular Response 1 (MR1) at Month 3

80.0 Percentage of participants Interval 71.5 to 88.5

SECONDARY outcome

Timeframe: Month 6

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

MR2 is defined as <= 1% BCR-ABL with a minimum of 3,000 ABL transcripts assessed by the central laboratory.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Molecular Response 2 (MR2) at Month 6

66.7 Percentage of participants Interval 56.7 to 76.7

SECONDARY outcome

Timeframe: Months 3, 6, 9 and 12

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

MR4.0 defined as either: detectable disease with <= 0.01% BCR-ABL with a minimum of 9,800 ABL transcripts assessed by the central laboratory, or undetectable disease in cDNA with a minimum of 9,800 ABL transcripts assessed by the central laboratory. MR4.5 defined as either: detectable disease with <= 0.0032% BCR-ABL with a minimum of 30,990 ABL transcripts assessed by the central laboratory or undetectable disease in cDNA with a minimum of 30,990 ABL transcripts assessed by the central laboratory. The MMR value counted only if the response was demonstrated at the designated visit; any MMR gained and lost, or never achieved at or before the designated visit was considered as non-responder.

Outcome measures

Measure	Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.0: Month 3	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.0: Month 6	18.3 Percentage of participants Interval 10.1 to 26.5
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.0: Month 9	25.0 Percentage of participants Interval 15.8 to 34.2
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.0: Month 12	31.7 Percentage of participants Interval 21.8 to 41.5
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.5: Month 3	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.5: Month 6	8.3 Percentage of participants Interval 2.5 to 14.2
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.5: Month 9	16.7 Percentage of participants Interval 8.8 to 24.6
Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 MR4.5: Month 12	21.7 Percentage of participants Interval 12.9 to 30.4

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Percentage of participants with MMR at Month 36. Cumulative incidence of MMR was measured from first dose to the first date of response. Documented participants who did not have an MMR response were censored at the last molecular assessment. A MMR is defined as <=0.1% BCR-ABL transcripts on the international scale, corresponding to a >=3-log reduction from standardized baseline with at least 3000 ABL assessed by the central laboratory. Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without the event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Major Molecular Response (MMR) at Month 36

70.0 Percentage of participants Interval 60.3 to 79.7

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Percentage of participants with MR4.0 at month 36. Cumulative incidence of MR4.0, was measured from first dose to the first date of MR 4.0. Documented participants who did not have an MR4.0 response were censored at the last molecular assessment. MR4.0 defined as either 1) detectable disease with <=0.01% BCR-ABL IS or 2) undetectable disease in cDNA with a minimum number of 9800 ABL transcripts specified by the central laboratory. Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without the event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Molecular Response 4.0 (MR4.0) at Month 36

50.0 Percentage of participants Interval 39.4 to 60.6

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Percentage of participants with MR4.5 at Month 36. Cumulative incidence of MR 4.5 was measured from first dose to the first date of MR 4.5. Documented participants who did not have an MR4.5 response were censored at the last molecular assessment. MR 4.5 defined as either 1) detectable disease with <=0.0032% BCR-ABL IS or 2) undetectable disease in cDNA with a minimum number of 30990 ABL transcripts specified by the central laboratory in the same volume of cDNA used to test for BCR-ABL. Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without the event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Molecular Response 4.5 (MR4.5) at Month 36

46.7 Percentage of participants Interval 36.1 to 57.3

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Percentage of participants with CCyR at Month 36. Cumulative incidence of CCyR, was measured from first dose to the first date of CCyR. Documented participants who did not have a CCyR response were censored at the last cytogenetic assessment. CCyR was defined as absence of detectable Philadelphia chromosome positive cells. CCyR was achieved when there were "0" Philadelphia chromosome positive metaphases among at least 20 metaphases from a bone marrow sample or when MMR was achieved if no bone marrow analysis was performed. Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without the event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Complete Cytogenetic Response (CCyR) at Month 36

80.0 Percentage of participants Interval 69.8 to 87.1

SECONDARY outcome

Timeframe: Up to Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

CHR is based on peripheral blood assessment: WBC <=10*10^9/L, basophils <5% in blood, no myelocytes, promyelocytes, myeloblasts in the blood differential, platelet count <450* 10^9/L, spleen non-palpable. In the absence of extramedullary disease info, it was assumed that spleen was non-palpable. If CHR could not be assessed due to one or more missing components of CHR and participant had a MMR or a CCyR and all assessed components of CHR were within appropriate limits, then CHR was imputed using CCyR or MMR. CHR must be of at least 4 weeks in duration and confirmed by 2 assessments at least 4 weeks apart.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Percentage of Participants With Cumulative Complete Haematological Response (CHR)

91.7 Percentage of participants Interval 85.8 to 97.5

SECONDARY outcome

Timeframe: At Month 36

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment.

Percentage of participants with transformation to AP and BP at Month 36. Transformation to AP or to BP CML defined as the time from first dose to the first date of transformation to accelerated phase or to blast phase CML. Documented participants who did not progress to AP or BP were censored at the last hematologic assessment. The transformation to AP or to BP was counted while participants were on treatment up to 28 days after last dose. Cumulative incidence: % of participants with event at month 36 adjusted for competing risk of treatment discontinuation without the event.

Outcome measures

Measure

Bosutinib n=60 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Cumulative Incidence of Transformation to Accelerated Phase (AP) and Blast Phase (BP) at Month 36

NA Percentage of participants Number and 90% CI was not estimable as there were no participants with events.

SECONDARY outcome

Timeframe: Maximum up to 44 months of treatment

Population: The modified as-treated population included all enrolled participants with Philadelphia chromosome positive CP CML harboring b2a2 and/or b3a2 transcripts who received at least 1 dose of study treatment. Here, ''Overall Number of Participants Analyzed'' signifies participants with mutation testing.

Mutation analysis was performed in case of either lack of response, suboptimal response or loss of response, or at the End of Treatment/Withdrawal visit.

Outcome measures

Measure

Bosutinib n=24 Participants Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.

Number of Participants With BCR-ABL Mutation at Treatment Discontinuation

0 Participants

Adverse Events

Bosutinib

Serious events: 14 serious events

Other events: 60 other events

Deaths: 2 deaths

Serious adverse events

Measure	Bosutinib n=60 participants at risk Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Eye disorders Diabetic retinopathy	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Diarrhoea	3.3% 2/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Vomiting	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
General disorders Pyrexia	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Hepatobiliary disorders Drug-induced liver injury	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Hepatobiliary disorders Liver disorder	3.3% 2/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Gastroenteritis	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Pneumonia	3.3% 2/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Pyelonephritis	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Sepsis	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Wound infection	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Alanine aminotransferase increased	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Aspartate aminotransferase increased	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Metabolism and nutrition disorders Dehydration	3.3% 2/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Renal and urinary disorders Acute kidney injury	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Drug eruption	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Erythema multiforme	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Ileus	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Influenza	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Injury, poisoning and procedural complications Ankle fracture	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Renal and urinary disorders Nephropathy toxic	1.7% 1/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.

Other adverse events

Measure	Bosutinib n=60 participants at risk Participants with newly diagnosed CP CML received bosutinib treatment, orally at a dose of 400 mg QD. In treatment phase, participants received bosutinib once daily for up to 12 months, which was extended further to at least additional 24 months (total of at least 36 months) or until end of the study, treatment failure, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. If participants discontinued the treatment phase only then they entered the long-term follow-up phase up to approximately 3 years after registration of the last participant, or until study termination, whichever comes first.
Blood and lymphatic system disorders Anaemia	16.7% 10/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Blood and lymphatic system disorders Lymphopenia	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Blood and lymphatic system disorders Thrombocytopenia	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Abdominal pain upper	10.0% 6/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Constipation	13.3% 8/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Diarrhoea	86.7% 52/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Nausea	28.3% 17/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Vomiting	26.7% 16/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
General disorders Pyrexia	25.0% 15/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Hepatobiliary disorders Liver disorder	11.7% 7/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Influenza	10.0% 6/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Nasopharyngitis	38.3% 23/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Upper respiratory tract infection	13.3% 8/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Alanine aminotransferase increased	55.0% 33/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Amylase increased	16.7% 10/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Aspartate aminotransferase increased	46.7% 28/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Blood alkaline phosphatase increased	26.7% 16/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Blood creatine phosphokinase increased	10.0% 6/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Gamma-glutamyltransferase increased	18.3% 11/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Lipase increased	28.3% 17/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Lymphocyte count decreased	11.7% 7/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Neutrophil count decreased	11.7% 7/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Platelet count decreased	21.7% 13/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations White blood cell count decreased	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Metabolism and nutrition disorders Hypocalcaemia	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Musculoskeletal and connective tissue disorders Back pain	16.7% 10/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Nervous system disorders Headache	11.7% 7/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Respiratory, thoracic and mediastinal disorders Pleural effusion	13.3% 8/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Dermatitis acneiform	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Eczema asteatotic	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Photosensitivity reaction	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Pruritus	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Rash	30.0% 18/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Rash maculo-papular	13.3% 8/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Gastrointestinal disorders Stomatitis	10.0% 6/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Infections and infestations Gastroenteritis	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Investigations Blood creatinine increased	10.0% 6/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Metabolism and nutrition disorders Hypokalaemia	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Musculoskeletal and connective tissue disorders Arthralgia	15.0% 9/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	8.3% 5/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Eczema	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Skin and subcutaneous tissue disorders Urticaria	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.
Vascular disorders Hypertension	6.7% 4/60 • From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months) The total number of deaths occurring during study, from first dose and up to end of the study are reported for all treated participants and includes deaths which occurred after 28 days post last study drug dose. Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety population evaluated.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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