Study Evaluating SKI-606 (Bosutinib) In Japanese Subjects... | NCT00811070

ID	Type	Description	Link
B1871007	Other Identifier	Alias Study Number

Label	Type	Description	Intervention Names
1	Experimental		Drug: SKI-606 (Bosutinib)

Name	Type	Description	Arm Group Labels	Other Names
SKI-606 (Bosutinib)	Drug	Formulation: 100 mg Capsule for Part 1, 100 mg tablet for Part1 and Part 2. SKI-606 (Bosutinib) will be taken by mouth with water and food as continuous once-daily dosing.

Measure	Description	Time Frame
Number of Participants With Dose-Limiting Toxicity (DLT) - Part 1	DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity.	Baseline up to Day 28 (Part 1 )
Maximum Tolerated Dose (MTD) - Part 1	MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT.	Baseline up to Day 28 (Part 1 )
Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Second-line Cohort - Part 2	Cytogenetic response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.	Week 24

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) - Part 1		Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15
Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Cytogenetic or Polymerase Chain Reaction based diagnosis of Chronic phase of Philadelphia Chromosome Positive Chronic Myelogenous Leukemia:

(Part 1), any phase of Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Part 2), whose disease is resistant/refractory to full-dose imatinib (400 mg for chronic phase subjects/600 mg for advanced leukemia subjects), or are intolerant of any dose of imatinib.

Adequate duration of prior imatinib therapy.
No prior exposure to Src, Abl, or Src/Abl kinase inhibitors other than imatinib.
Eastern Cooperative Oncology Group Performance Status of 0 or 1 for chronic phase subjects, and 0, 1 or 2 for Advanced Stage subjects.
At least 7 days since any anti-proliferative treatment (including intrathecal chemotherapy) before the first dose of SKI-606, (except hydroxyurea).
Recovered to National Cancer Institute grade 0-1, or to baseline, from any toxicities of prior anti-tumor treatment, other than alopecia or thrombocytopenia due to active prior treatment (intolerant subjects).
At least 3 months post allogeneic stem cell transplantation before the first dose of SKI-606.
Able to take daily oral capsules reliably.
Absolute neutrophil count greater than 1,000/mL (Part 1)
Adequate hepatic, and renal function.
Documented normal INR if not on oral anticoagulant therapy, or, if on oral anticoagulant therapy consistent target INR less than 3.
Age should be greater than 20 years and less than 75 years (Part 1), greater than 20 years (Part 2), including women of childbearing potential.
Willingness of male and female subjects, who are not surgically sterile or postmenopausal, must agree and commit to the use of reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of SKI-606.

Exclusion Criteria:

Subjects with Philadelphia chromosome negative Chronic Myelogenous Leukemia.
Overt leptomeningeal leukemia. Subjects must be free of CNS involvement according to the symptoms for a minimum of 2 months before the first dose of SKI-606. Subjects with CNS symptoms must have a diagnostic lumbar puncture prior to study enrollment.
Subjects with extramedullary disease only.
Ongoing requirement for warfarin or other oral anticoagulant therapy (Part 1).
Ongoing requirement for hydroxyurea (Part 1).
Graft Versus Host Disease. a. no previous Graft Versus Host Disease allowed (Part 1). b. no treated or untreated Graft Versus Host Disease within 60 days of first dose (Part 2).
Major surgery within 14 days or radiotherapy within 7 days before the first dose of SKI-606 (recovery from any previous surgery should be complete before day 1).
Ongoing clinical requirement for administration of a strong inhibitor or inducer of CYP-3A4 (Part 1).
History of clinically significant or uncontrolled cardiac disease including: a. history of a clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) b. diagnosed or suspected congenital or acquired prolonged QT syndrome c. history of prolonged QTc d. unexplained syncope e. history of or active congestive heart failure f. myocardial infarction within 12 months. g. Uncontrolled angina or hypertension within 3 months.
Baseline QTcF greater than 0.45 sec (average of triplicate readings).
Concomitant use of or need for medications known to prolong the QT interval.
Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval.
Recent (within 14 days before the first dose of SKI-606) or ongoing clinically significant gastrointestinal disorder.
Pregnant or breastfeeding women.
Evidence of serious active infection, or significant medical or psychiatric illness.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Kumamoto University Hospital		Kumamoto	Kumamoto	860-8556	Japan
Tohoku University Hospital

PubMed Identifier	Type	Citation	Retractions
35235189	Derived	Takahashi N, Cortes JE, Sakaida E, Ishizawa K, Ono T, Doki N, Matsumura I, Garcia-Gutierrez V, Rosti G, Ono C, Ohkura M, Tanetsugu Y, Viqueira A, Brummendorf TH. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol. 2022 Jun;115(6):838-851. doi: 10.1007/s12185-022-03314-y. Epub 2022 Mar 2.
28409328

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose-Limiting Toxicity (DLT) - Part 1

DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity.

Participants enrolled in Part 1 of the study were analyzed for DLT. Two participants (1 each in the 400 mg and 500 mg) who discontinued the treatment by Day 28 due to non-safety reasons were excluded from the analysis.

Posted

Number

Participants

Baseline up to Day 28 (Part 1 )

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG002	Bosutinib Second-line 600 mg (Part 1 )	Single oral dose of bosutinib 600 mg on Day 1 and then bosutinib 600 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred.

Units	Counts
Participants	OG0006 OG0016 OG0023

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0011 OG0020

Primary

Maximum Tolerated Dose (MTD) - Part 1

MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT.

Posted

Number

Baseline up to Day 28 (Part 1 )

ID	Title	Description
OG000	All Treated Participants (Part 1 )	All participants who received single oral dose of bosutinib 400 mg, 500 mg or 600 mg on Day 1 and then bosutinib 400 mg, 500 mg or 600 mg orally once daily continuously from Day 3 up to Week 4.

Units	Counts
Participants	OG000

Secondary

Maximum Observed Plasma Concentration (Cmax) - Part 1

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

n= number of participants analyzed.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

n= number of participants analyzed.

Posted

Median

Full Range

hour

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Plasma Decay Half-Life (t1/2) - Part 1

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

Posted

Mean

Standard Deviation

hour

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Area Under the Concentration-Time Curve (AUC) - Part 1

Area under the plasma concentration time-curve from zero to infinity. AUC on Day 15 was assessed as the steady state AUC.

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

n= number of participants analyzed.

Posted

Mean

Standard Deviation

nanogram*hour per milliliter (ng•hr/mL)

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Apparent Oral Clearance (CL/F) - Part 1

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F on Day 15 was assessed as the steady state CL/F.

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

n= number of participants analyzed.

Posted

Mean

Standard Deviation

L/hr

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Apparent Volume of Distribution (Vz/F) - Part 1

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

Posted

Mean

Standard Deviation

liter

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Accumulation Ratio (R) - Part 1

R=accumulation ratio (AUCss on Day 15/AUC[0-24] on Day 1)

The pharmacokinetic parameter population was defined as all participants who received at least 1 dose of bosutinib and had at least 1 of the pharmacokinetic parameters of interest.

Posted

Mean

Standard Deviation

ratio

Before and 1, 2, 3, 4, 6, 8, 24 and 48 hours after administration on Day 1, and before and 1, 2, 3, 4, 6, 8, and 24 hours after administration on Day 15

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Primary

Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Second-line Cohort - Part 2

Cytogenetic response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Maintained Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Second-line and Third-line Cohort - Part 2

Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.

The responder for maintained MCyR included 'participants without baseline response who had a response at a specified time' and 'participants with baseline response who had a post-baseline response either maintained or improved at a specified time'.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 - Part 1

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
OG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.

Secondary

Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Third-line Cohort - Part 2

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Week 24

ID	Title	Description
OG000	Bosutinib Exploratory Third-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic or accelerated or blast phase third-line imatinib resistant/refractory/intolerant followed by dasatinib or nilotinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Time to Major Cytogenetic Response (MCyR) in Chronic Phase Second-line and Third-line Cohort - Part 2

Time to MCyR was the interval from the date of first dose of study medication until the first date of achieving a given response.

Time to response in weeks = (event date minus first dose date plus 1)/7, where the event date is the non-missing date of the first attained response or last cytogenetic assessment date of a participants.

Subset of participants who had the response among all treated population

Posted

Median

95% Confidence Interval

weeks

204 weeks in the second-line participants and 48 weeks in the third-line participants

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Exploratory Third-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic or accelerated or blast phase third-line imatinib resistant/refractory/intolerant followed by dasatinib or nilotinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Second-line and Third-line Cohort - Part 2

Duration of MCyR was defined as the interval from the date of the earliest demonstration of a response, until the earliest date of loss of that response. Duration of response in weeks = (date of confirmed loss of first attained response minus date of first attained response)/7 days.

Subset of participants who had the response among all treated population

Posted

Median

95% Confidence Interval

weeks

204 weeks in the second-line participants and 48 weeks in the third-line participants

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Exploratory Third-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic or accelerated or blast phase third-line imatinib resistant/refractory/intolerant followed by dasatinib or nilotinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Percentage of Participants With Complete Hematologic Response (CHR) up to Week 192 in Advance Phase Second-line Cohort - Part 2

CHR response was considered to be achieved if participants met all of the following criteria: White Blood Cells =< institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count >=1.0*10^9 per liter (/L), platelets >=100 but <450*10^9/L, <20% basophils in blood and no extramedulary involvement (including hepato- or splenomegaly), =<5% BM blasts.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Time to Achieve Complete Hematologic Response (CHR) in Advanced Phase Second-line Cohort - Part 2

The time to CHR was measured from the date of first dosing to the first date of response. Time to response in weeks = (event date - first dose date plus 1)/7, where the event date is the non-missing date of the first attained response or last assessment date of a participant.

Subset of participants who had the response among all treated population.

Posted

Median

95% Confidence Interval

weeks

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Duration of Complete Hematologic Response (CHR) in Advanced Phase Second-line Cohort - Part 2

The duration of CHR was defined as the interval from the first date of response until the first date of confirmed loss of response. Duration of response in weeks =(date of confirmed loss of first attained response - date of first attained response)/7.

Subset of participants who had the response among all treated population

Posted

Median

95% Confidence Interval

weeks

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Overall Hematologic Response (OHR) Up to Week 192 in Accelerated Phase/Blast Phase Third-line Cohort - Part 2

OHR included CHR, no evidence of leukemia (NEL), minor hematologic response (MiHR) or return to chronic phase (RCP), participants had to meet at least 1 of this criterion. Criteria for RCP: disappearance of features defining AP/BP, but still in CP and persistence of clonal evolution. Criteria for MiHR: <15% blasts in blood and bone marrow, <30% blasts+promyelocytes in blood and bone marrow, <20% basophils in blood, no extramedullary disease other than liver/spleen. Criteria for CHR and NEL: <20% basophils in blood, no extramedullary involvement including liver/spleen, no peripheral blasts or promyelocytes, myelocytes + metamyelocytes <5% in blood, <5% (NEL) and <=5% (CHR) marrow blasts, 0.5*10^9 <= Absolute neutrophil count (ANC) <1.0*10^9/L (NEL) and ANC>=1.0*10^9/L (CHR), 20*10^9 <=platelets<100 *10^9/L (NEL) and platelets>=100 but <450x10^9/L (CHR), white blood cells <=institutional upper limit of the normal range.

Subset of the third-line cohort who was in accelerated or blast phase

Posted

Number

percentage of participants

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Exploratory Third-line 500 mg - AP/BP (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase (AP/BP) third-line imatinib resistant/intolerant followed by dasatinib or nilotinib resistant/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Time to Achieve Overall Hematologic Response (OHR) in Accelerated Phase/Blast Phase Third-line Cohort - Part 2

The time to OHR was measured from the date of first dosing to the first date of response. Time to response in weeks = (event date - first dose date plus 1)/7, where the event date is the non-missing date of the first attained response or last assessment date of a participant.

Subset of participants who had the response among all treated population and who was in accelerated or blast phase in the third-line cohort

Posted

Median

95% Confidence Interval

weeks

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Exploratory Third-line 500 mg - AP/BP (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase (AP/BP) third-line imatinib resistant/intolerant followed by dasatinib or nilotinib resistant/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Duration of Overall Hematologic Response (OHR) in Accelerated Phase/Blast Phase Third-line Cohort - Part 2

The duration of OHR was defined as the interval from the first date of response until the first date of confirmed loss of response. Duration of response in weeks =(date of confirmed loss of first attained response - date of first attained response)/7.

Subset of participants who had the response among all treated population and who was in accelerated or blast phase in the third-line cohort

Posted

Median

95% Confidence Interval

weeks

Baseline up to Week 192

ID	Title	Description
OG000	Bosutinib Exploratory Third-line 500 mg - AP/BP (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase (AP/BP) third-line imatinib resistant/intolerant followed by dasatinib or nilotinib resistant/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Units	Counts
Participants	OG000

Secondary

Time to Treatment Failure (TTF) Rate - Part 2

TTF was the interval from the date of first dose of bosutinib until the earlier date of progression or death (any cause), withdrawal from treatment owing to an AE, subject refusal, or loss to follow-up (censored at the last contact date), or further anti-tumor therapy before documented progression (whichever occurred first). TTF rate indicates the probability of no treatment failure. Percent of participants with no treatment failure were estimated.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Date of first dose of study drug up to Week 336 in primary second line participants; up to Week 192 in advanced second line and exploratory third line participants

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Progression-free Survival (PFS) Rate - Part 2

PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to treatment discontinuation due to disease progression as assessed by the investigator. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from death case report forms (CRFs). Percent of participants with PFS were estimated.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Date of first dose of study drug up to Week 336 in primary second line participants; up to Week 192 in advanced second line and exploratory third line participants

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.

Secondary

Overall Survival (OS) Rate - Part 2

OS was based on Kaplan-Meier method. Survival was defined as the time period from the date of first dose of bosutinib to the date of death, censored at the participant's last contact date. Percent of participants with OS were estimated.

All treated population was defined as all participants who received at least 1 dose of bosutinib.

Posted

Number

95% Confidence Interval

percentage of participants

Date of first dose of study drug up to Week 336 in primary second line participants; up to Week 192 in advanced second line and exploratory third line participants

ID	Title	Description
OG000	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG001	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
OG002	Bosutinib Exploratory Third-line 500 mg (Part 2 )

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Cataract	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Macular fibrosis	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Liver injury	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Pertussis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Blast cell crisis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Renal impairment	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0010 affected11 at risk EG0022 affected63 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Macular hole	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Diverticulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Completed suicide	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Alveolitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0010 affected11 at risk EG0021 affected63 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected52 at risk EG0010 affected11 at risk EG00213 affected63 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00011 affected52 at risk EG0012 affected11 at risk EG00213 affected63 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00019 affected52 at risk EG0015 affected11 at risk EG00224 affected63 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00012 affected52 at risk EG0012 affected11 at risk EG00214 affected63 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected52 at risk EG0012 affected11 at risk EG00218 affected63 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0010 affected11 at risk EG0027 affected63 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0012 affected11 at risk EG0029 affected63 at risk
Cheilitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0010 affected11 at risk EG0027 affected63 at risk
Dental caries	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected52 at risk EG0012 affected11 at risk EG00211 affected63 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00050 affected52 at risk EG00110 affected11 at risk EG00260 affected63 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0012 affected11 at risk EG0025 affected63 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0010 affected11 at risk EG0027 affected63 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00019 affected52 at risk EG0015 affected11 at risk EG00224 affected63 at risk
Proctalgia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00011 affected52 at risk EG0011 affected11 at risk EG00212 affected63 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected52 at risk EG0011 affected11 at risk EG00223 affected63 at risk
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0011 affected11 at risk EG0028 affected63 at risk
Malaise	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG00012 affected52 at risk EG0010 affected11 at risk EG00212 affected63 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected52 at risk EG0012 affected11 at risk EG0029 affected63 at risk
Liver disorder	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Folliculitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0008 affected52 at risk EG0010 affected11 at risk EG0028 affected63 at risk
Gingivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0011 affected11 at risk EG0027 affected63 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0005 affected52 at risk EG0010 affected11 at risk EG0025 affected63 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00030 affected52 at risk EG0016 affected11 at risk EG00236 affected63 at risk
Otitis media	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Periodontitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Pharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0005 affected52 at risk EG0010 affected11 at risk EG0025 affected63 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Post-traumatic neck syndrome	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00020 affected52 at risk EG0014 affected11 at risk EG00224 affected63 at risk
Amylase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0011 affected11 at risk EG0027 affected63 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00015 affected52 at risk EG0014 affected11 at risk EG00219 affected63 at risk
Blood albumin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0009 affected52 at risk EG0012 affected11 at risk EG00211 affected63 at risk
Blood bilirubin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Blood creatine phosphokinase decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0012 affected11 at risk EG0028 affected63 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0008 affected52 at risk EG0010 affected11 at risk EG0028 affected63 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0012 affected11 at risk EG0026 affected63 at risk
Blood sodium decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0009 affected52 at risk EG0011 affected11 at risk EG00210 affected63 at risk
Haemoglobin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0010 affected11 at risk EG0026 affected63 at risk
Lipase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00011 affected52 at risk EG0014 affected11 at risk EG00215 affected63 at risk
Liver function test abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Neutrophil count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0009 affected52 at risk EG0010 affected11 at risk EG0029 affected63 at risk
White blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected52 at risk EG0011 affected11 at risk EG00215 affected63 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected52 at risk EG0010 affected11 at risk EG00213 affected63 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0012 affected11 at risk EG0025 affected63 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0011 affected11 at risk EG0025 affected63 at risk
Somnolence	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Renal impairment	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Urogenital haemorrhage	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0012 affected11 at risk EG0028 affected63 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected52 at risk EG0010 affected11 at risk EG0025 affected63 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0011 affected11 at risk EG0025 affected63 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0010 affected11 at risk EG0026 affected63 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Generalised erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Leukoderma	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0012 affected11 at risk EG0023 affected63 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0012 affected11 at risk EG0028 affected63 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected52 at risk EG0015 affected11 at risk EG00236 affected63 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected52 at risk EG0010 affected11 at risk EG0025 affected63 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected52 at risk EG0010 affected11 at risk EG0026 affected63 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Pericardial effusion	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Cataract	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Conjunctivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0011 affected11 at risk EG0024 affected63 at risk
Epididymitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Herpes zoster	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0003 affected52 at risk EG0010 affected11 at risk EG0023 affected63 at risk
Blood potassium increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Blood uric acid increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Weight increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk
Dysgeusia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected52 at risk EG0011 affected11 at risk EG0022 affected63 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected52 at risk EG0010 affected11 at risk EG0024 affected63 at risk
Erythema nodosum	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected52 at risk EG0011 affected11 at risk EG0021 affected63 at risk
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected52 at risk EG0011 affected11 at risk EG0023 affected63 at risk

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Bosutinib Second-line 400 mg (Part 1 )	Single oral dose of bosutinib 400 mg on Day 1 and then bosutinib 400 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
BG001	Bosutinib Second-line 500 mg (Part 1 )	Single oral dose of bosutinib 500 mg on Day 1 and then bosutinib 500 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy after the safety confirmation of 600 mg cohort.
BG002	Bosutinib Second-line 600 mg (Part 1 )	Single oral dose of bosutinib 600 mg on Day 1 and then bosutinib 600 mg orally once daily was administered continuously from Day 3 in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML) until disease progression, unacceptable toxicity, or withdrawal of consent occurred.
BG003	Bosutinib Primary Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML).Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
BG004	Bosutinib Advanced Second-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with accelerated or blast phase second-line imatinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
BG005	Bosutinib Exploratory Third-line 500 mg (Part 2 )	Bosutinib 500 mg was administered orally once-daily in participants with chronic or accelerated or blast phase third-line imatinib resistant/refractory/intolerant followed by dasatinib or nilotinib resistant/refractory/intolerant chronic myelogenous leukemia (CML). Intra-subject dose escalation up to 600 mg was allowed for lack of efficacy.
BG006	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Total Second-line	All participants who received bosutinib orally once daily in second-line chronic myelogenous leukemia (CML), who were imatinib resistant/refractory/intolerant.	19	52	52	52
EG001	Exploratory Third-line	All participants who received bosutinib 500 mg orally once daily in third-line chronic myelogenous leukemia (CML), participants were with imatinib resistant/refractory/intolerant followed by dasatinib or nilotinib resistant/refractory/intolerant.	2	11	11	11
EG002	Total Population	Total participants who were second-line or third-line chronic myelogenous leukemia (CML).	21	63	63	63