Dasatinib (BMS-354825) in Subjects With Myeloid Blast Pha... | NCT00101816

Label	Type	Description	Intervention Names
1	Experimental		Drug: Dasatinib

Name	Type	Description	Arm Group Labels	Other Names
Dasatinib	Drug	Tablets, Oral, 70 mg, twice daily, Until disease progression or intolerable toxicity, switch to the roll-over study or study closure.	1

Measure	Description	Time Frame
Major and Overall Hematologic Response (MaHR and OHR)	MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= <15% blasts in bone marrow and <15% blasts in peripheral blood (PB); <30% blasts + promyelocytes in bone marrow and <30% blasts + promyelocytes in PB; <20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.	Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

Measure	Description	Time Frame
Median Duration of Major Hematologic Response (MaHR)	MaHR=best confirmed response of CHR or NEL. CHR=white blood cells ≤ institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤ iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement; at least 1 of the following: ANC ≥500/mm3 & <1000/mm3; platelets ≥20,000/mm3 & <100,000/mm3.

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Local Institution		Birmingham	Alabama		United States
Local Institution

PubMed Identifier	Type	Citation	Retractions
17185463	Background	Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P, Branford S, Agarwal P, Gollerkeri A, Baccarani M. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood. 2007 Apr 15;109(8):3207-13. doi: 10.1182/blood-2006-09-046888. Epub 2006 Dec 21.
18477770

ID	Title	Description
FG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.

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

Major and Overall Hematologic Response (MaHR and OHR)

MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= <15% blasts in bone marrow and <15% blasts in peripheral blood (PB); <30% blasts + promyelocytes in bone marrow and <30% blasts + promyelocytes in PB; <20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.

All treated subjects

Posted

Number

Participants

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
OG002	Total

Units	Counts
Participants	OG00010 OG00199 OG002109

Title

Denominators

Categories

MaHR

Title	Measurements
	OG0002 OG00134 OG00236

OHR

Secondary

Median Duration of Major Hematologic Response (MaHR)

MaHR=best confirmed response of CHR or NEL. CHR=white blood cells ≤ institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤ iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; <5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement; at least 1 of the following: ANC ≥500/mm3 & <1000/mm3; platelets ≥20,000/mm3 & <100,000/mm3.

Participants who achieved MaHR

Posted

Median

Full Range

months

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

ID	Title	Description
OG000	Participants Acheiving MaHR	MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL)

Units	Counts
Participants	OG000

Secondary

Median Duration of Overall Hematologic Response (OHR)

OHR=best confirmed response of MaHR or MiHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1. Maintaining a response was defined as no 2 consecutive records of non-response (ie, a single record of non-response between 2 assessments of response was not considered a loss of response).

Participants who achieved OHR

Posted

Median

95% Confidence Interval

months

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

ID	Title	Description
OG000	Participants Acheiving OHR	OHR=best confirmed response of major or minor hematologic response

Units	Counts
Participants	OG000

Secondary

Time to MaHR and OHR

Median time from first dosing to date of OHR and/or MaHR in subjects who achieved OHR and MaHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1.

Participants who achieved OHR and MaHR

Posted

Median

95% Confidence Interval

days

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

ID	Title	Description
OG000	Participants Acheiving MaHR	MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL)
OG001	Participants Acheiving OHR	OHR=best confirmed response of major or minor hematologic response (MaHR or MiHR).

Units	Counts
Participants

Secondary

Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response

Best confirmed cytogenetic response. Determination of cytogenetic response is based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).

All treated subjects

Posted

Number

Participants

Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.

Secondary

Number of Participants With CHR or NEL, MiHR, or no Hematologic Response

Best confirmed hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for complete hematologic response (CHR) or No Evidence of Leukemia (NEL) are specified in Outcome Measure 2. Criteria for minor hematologic response (MiHR) are specified in Outcome Measure 1.

All treated subjects

Posted

Number

Participants

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatment

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.

Secondary

Number of Participants Achieving Major Molecular Response (MMR)

Number of participants who achieved an MMR at any time during the treatment period. MMR was calulated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).

treated participants with or without CCyR who were assessed for major molecular response

Posted

Number

participants

Baseline, every 12 weeks, and at time of Complete Cytogenetic Response (CCyR) for quantitative Polyermase Chain Reaction (qPCR) analysis

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.

Secondary

MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations

MaHR and MCyR in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). Criteria for MaHR are specified in Outcome Measure 2. MCyR=rate of complete cytogenetic responses + the rate of partial cytogenetic responses, as defined in Outcome Measure 5. BCR-ABL=the fused gene found in subjects with this type of CML. This table contains those mutations observed in at least 3 participants. The categories "1 IRM w/2-4-fold increase in resistance" and "≥1 IRM w/≥5-fold increase in resistance" refer to increase in resistance to imatinib.

All subjects with baseline mutation data; n=the number of participants with the specified mutation. Baseline mutation data were reported for 103 of the 109 subjects (10/10 imatinib-intolerant and 93/99 imatinib-resistant). At baseline, 39 (42%) imatinib-resistant subjects and 3 imatinib-intolerant subject had imatinib-resistant mutations

Posted

Number

Percentage of Participants

baseline, at time of disease progression

ID	Title	Description
OG000	MaHR	Participants acheiving MaHR, defined as best confirmed response of Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL) of Minore Hematologic Response (MiHR)
OG001	MCyR	Participants acheiving MCyR, defined as the rate of CCyR plus the rate of Partial Cytogenetic Response

Secondary

Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)

Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). Score range: 0-108; higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, & SWB score change of 2 or more=minimal clinical important change.

Number of participants with FACT-G assessments at baseline and at least one assessment during treatment

Posted

Number

Participants

Baseline, Every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.

Secondary

Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)

All treated subjects

Posted

Number

Participants

Continuously throughout study, from pre-treatment visit through end of study (due to death, unacceptable toxicity, treatment failure, etc) and follow-up period

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant

Secondary

Pharmacokinetics (PK) of Dasatinib - Maximum Observed Plasma Concentration (Cmax)

The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.

26 participants had dense PK sampling on Day 1 and Day 8; parameters for 1 participant on Day 8 was excluded due to unreliable data. Participants with all concentration-time values < than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.

Posted

Mean

Standard Deviation

ng/mL

Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Dasatinib - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h or 24 h(AUC[0-T])

The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were < lower limit of qualtitation were assigned a value of zero.

Posted

Mean

Standard Deviation

ng∙h/mL

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Dasatinib - Time to Maximum Observed Plasma Concentration (Tmax)

The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Dasatinib - Plasma Half-life (T-HALF)

The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)

26 participants had dense PK sampling on Day 1 & Day 8; parameters for 1 participant on Day 1 & 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \

Posted

Mean

Standard Deviation

ng/mL

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants

Secondary

Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h (AUC[0-T])

The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.

26 participants had dense PK sampling on Day 1 & Day 8; parameters for 1 participant on Day 1 & 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \

Posted

Mean

Standard Deviation

ng∙h/mL

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001

Secondary

Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)

26 participants had dense PK sampling on Day 1 & Day 8; parameters for 1 participant on Day 1 & 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001

Secondary

Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)

The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.

26 participants had dense PK sampling on Day 1 & Day 8; parameters for 1 participant on Day 1 & 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Study Day 1
OG001	Study Day 8

Units	Counts
Participants	OG000

Secondary

Population PK of Dasatinib

Population pharmacokinetic analysis was not done because it is not meaningful for this single study

Posted

Number

population pk

Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.

ID	Title	Description
OG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
OG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
TROPONIN I	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HAEMOGLOBIN	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HAEMOGLOBIN DECREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
CARDIAC ENZYMES INCREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
BLAST CELL COUNT INCREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
GRANULOCYTE COUNT DECREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PLATELET AGGREGATION ABNORMAL	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ELECTROCARDIOGRAM QT CORRECTED INTERVAL PROLONGED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
ANGINA UNSTABLE	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
NODAL ARRHYTHMIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
SINUS TACHYCARDIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
MYOCARDIAL ISCHAEMIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PERICARDIAL EFFUSION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0014 affected99 at risk
MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
CONGESTIVE CARDIOMYOPATHY	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CARDIAC FAILURE CONGESTIVE	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
ACUTE MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
ARRHYTHMIA SUPRAVENTRICULAR	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LEFT VENTRICULAR DYSFUNCTION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
SUPRAVENTRICULAR TACHYCARDIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
FLUSHING	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
THROMBOPHLEBITIS	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HEPATOSPLENOMEGALY	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CHOLECYSTITIS ACUTE	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CYTOLYTIC HEPATITIS	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
APHASIA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
HEADACHE	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
MYELITIS	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CONVULSION	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CEREBRAL ISCHAEMIA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CEREBRAL HAEMORRHAGE	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0014 affected99 at risk
MENINGITIS NONINFECTIVE	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
TRANSIENT ISCHAEMIC ATTACK	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
INTRACRANIAL PRESSURE INCREASED	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
DEPRESSED LEVEL OF CONSCIOUSNESS	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
ASCITES	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
MELAENA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
VOMITING	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HAEMATOCHEZIA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
GINGIVAL BLEEDING	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
NEUTROPENIC COLITIS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ABDOMINAL PAIN LOWER	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LARGE INTESTINAL ULCER	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0019 affected99 at risk
LOWER GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
SEPSIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00111 affected99 at risk
GANGRENE	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
PNEUMONIA	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0016 affected99 at risk
CELLULITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
PHARYNGITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
BRAIN ABSCESS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LIVER ABSCESS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ANAL INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LUNG INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PYELONEPHRITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CATHETER SEPSIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PERIANAL ABSCESS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ASCITES INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LOCALISED INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
DIARRHOEA INFECTIOUS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
NEUTROPENIC INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
CYTOMEGALOVIRUS COLITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ENTEROCOLITIS INFECTIOUS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CYTOMEGALOVIRUS INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
RENAL FAILURE	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
NEPHROLITHIASIS	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
RENAL IMPAIRMENT	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
INTESTINAL STOMA	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
STEM CELL TRANSPLANT	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
BONE MARROW TRANSPLANT	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
ANOREXIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HYPERCALCAEMIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0014 affected99 at risk
LEUKOCYTOSIS	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
PANCYTOPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
SPLENOMEGALY	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0015 affected99 at risk
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00110 affected99 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PURPURA	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
PETECHIAE	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
DECUBITUS ULCER	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
URTICARIA VESICULOSA	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
HAEMORRHAGE SUBCUTANEOUS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ACUTE FEBRILE NEUTROPHILIC DERMATOSIS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
FRACTURE	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
FEMUR FRACTURE	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
SUBDURAL HAEMATOMA	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
BONE PAIN	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
VERTEBRAL COLUMN MASS	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected99 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0016 affected99 at risk
ORTHOPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
CHYLOTHORAX	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00117 affected99 at risk
LUNG INFILTRATION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0014 affected99 at risk
LUNG CONSOLIDATION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
PULMONARY HYPERTENSION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
ACUTE RESPIRATORY DISTRESS SYNDROME	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PAIN	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
FATIGUE	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
MALAISE	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PYREXIA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00117 affected99 at risk
ASTHENIA	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
CHEST PAIN	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
GENERALISED OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
DISEASE PROGRESSION	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
MUCOSAL INFLAMMATION	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
PERFORMANCE STATUS DECREASED	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
TUMOUR PAIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
MYELOFIBROSIS	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected99 at risk
BLAST CELL CRISIS	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
TUMOUR LYSIS SYNDROME	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
BLAST CELL PROLIFERATION	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected99 at risk
CHRONIC MYELOID LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00118 affected99 at risk
BLAST CRISIS IN MYELOGENOUS LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0019 affected99 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DRY EYE	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
EYE OEDEMA	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
EYELID OEDEMA	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
EYE HAEMORRHAGE	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
RETINAL HAEMORRHAGE	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0018 affected99 at risk
CARDIAC MURMUR	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
WEIGHT DECREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0005 affected10 at risk EG00125 affected99 at risk
WEIGHT INCREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00121 affected99 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
ELECTROCARDIOGRAM QT CORRECTED INTERVAL PROLONGED	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
TACHYCARDIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0017 affected99 at risk
TACHYARRHYTHMIA	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
PERICARDIAL EFFUSION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
LEFT VENTRICULAR DYSFUNCTION	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
HAEMATOMA	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0017 affected99 at risk
HYPOTENSION	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00113 affected99 at risk
HYPERTENSION	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00112 affected99 at risk
PERIPHERAL ISCHAEMIA	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
ANXIETY	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0018 affected99 at risk
INSOMNIA	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00113 affected99 at risk
AGITATION	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
DEPRESSION	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0018 affected99 at risk
DEPRESSED MOOD	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0011 affected99 at risk
CONFUSIONAL STATE	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
CHOLELITHIASIS	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
GALLBLADDER ENLARGEMENT	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
HEPATIC FUNCTION ABNORMAL	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
ALLERGY TO ARTHROPOD BITE	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
COMA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
APHASIA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
HEADACHE	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00131 affected99 at risk
LETHARGY	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
DIZZINESS	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00114 affected99 at risk
CONVULSION	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
SOMNOLENCE	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
PARAESTHESIA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
HYPOAESTHESIA	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00134 affected99 at risk
ASCITES	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
VOMITING	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected10 at risk EG00137 affected99 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected10 at risk EG00160 affected99 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00111 affected99 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
PROCTALGIA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00114 affected99 at risk
ANAL FISSURE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00121 affected99 at risk
HAEMORRHOIDS	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0017 affected99 at risk
HAEMATOCHEZIA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0015 affected99 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00122 affected99 at risk
INGUINAL HERNIA	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
LIP HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
GINGIVAL BLEEDING	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
MOUTH HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0016 affected99 at risk
RECTAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00116 affected99 at risk
GASTROINTESTINAL DISORDER	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00110 affected99 at risk
RHINITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
PNEUMONIA	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
ORAL HERPES	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
PHARYNGITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
FOLLICULITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0016 affected99 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0017 affected99 at risk
ORAL CANDIDIASIS	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
VAGINAL INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
LOCALISED INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
CLOSTRIDIAL INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
FUNGAL SKIN INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0018 affected99 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
URINARY TRACT INFECTION BACTERIAL	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
ESCHERICHIA URINARY TRACT INFECTION	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
ANOREXIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00125 affected99 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
FLUID OVERLOAD	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00114 affected99 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0013 affected99 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00113 affected99 at risk
SPLENOMEGALY	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00117 affected99 at risk
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
ACNE	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00125 affected99 at risk
PURPURA	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0018 affected99 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00110 affected99 at risk
PETECHIAE	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00112 affected99 at risk
ECCHYMOSIS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00110 affected99 at risk
SKIN ULCER	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
SKIN LESION	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
NIGHT SWEATS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0019 affected99 at risk
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0014 affected99 at risk
SPIDER NAEVUS	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
SWELLING FACE	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
PERIORBITAL OEDEMA	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0018 affected99 at risk
NIPPLE PAIN	Reproductive system and breast disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
VAGINAL HAEMORRHAGE	Reproductive system and breast disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
CONTUSION	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
SKIN LACERATION	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00111 affected99 at risk
MYOSITIS	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00115 affected99 at risk
BONE PAIN	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00116 affected99 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00115 affected99 at risk
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0015 affected99 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00117 affected99 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00140 affected99 at risk
RALES	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0015 affected99 at risk
HYPOXIA	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG0012 affected99 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected10 at risk EG00130 affected99 at risk
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00121 affected99 at risk
HAEMOPTYSIS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0016 affected99 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0016 affected99 at risk
NASAL DISORDER	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
PLEURITIC PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00134 affected99 at risk
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0018 affected99 at risk
PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0015 affected99 at risk
THROAT TIGHTNESS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
PULMONARY THROMBOSIS	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
PHARYNGOLARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG0017 affected99 at risk
PULMONARY HYPERTENSION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
RESPIRATORY TRACT CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
PAIN	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG00112 affected99 at risk
CHILLS	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected10 at risk EG00112 affected99 at risk
OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0019 affected99 at risk
FATIGUE	General disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00134 affected99 at risk
PYREXIA	General disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected10 at risk EG00162 affected99 at risk
ASTHENIA	General disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected10 at risk EG00125 affected99 at risk
CHEST PAIN	General disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG00113 affected99 at risk
FACE OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0014 affected99 at risk
HYPOTHERMIA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected99 at risk
PITTING OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected99 at risk
LOCALISED OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG0014 affected99 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected10 at risk EG00135 affected99 at risk
GENERALISED OEDEMA	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected99 at risk
MUCOSAL INFLAMMATION	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected10 at risk EG0015 affected99 at risk
INFLUENZA LIKE ILLNESS	General disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected10 at risk EG0011 affected99 at risk

ID	Term
D015464	Leukemia, Myelogenous, Chronic, BCR-ABL Positive
D001752	Blast Crisis

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
D002471	Cell Transformation, Neoplastic
D063646	Carcinogenesis
D009385	Neoplastic Processes

ID	Term
D013844	Thiazoles
D013457	Sulfur Compounds
D009930	Organic Chemicals
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011743	Pyrimidines

ID	Title	Description
BG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
BG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Imatinib-intolerant	Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only <400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.			7	10	10	10
EG001	Imatinib-resistant	Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to <600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.			80	99	97	99