Guadecitabine (SGI-110) vs Treatment Choice in Adults Wit... | NCT02907359

NCT02907359

ID	Type	Description	Link
2015-005257-12	EudraCT Number

Status Module

Description Module

Detailed Description

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 participants will be randomly assigned 2:1 to either guadecitabine or TC.

Guadecitabine: approximately 272 participants.
TC: approximately 136 participants.

Before randomization, the investigator will assign each participant to one of the following TC options:

Low dose cytarabine (LDAC).
Standard Intensive Chemotherapy (IC) of a 7+3 regimen.
Best Supportive Care (BSC) only. BSC will be provided to all participants as per standard and institutional practice. Participants randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts >10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.

Guadecitabine: 60 milligrams per square meter (mg/m^2) given subcutaneously (SC) daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the participant continues to benefit. BSC should be given according to standard and institutional practice.

Treatment Choice (TC): Before randomization, the investigator will assign each participant to one of the following TC options:

Low dose cytarabine (LDAC) given as 20 mg/m^2 SC or intravenously (IV) once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity.
Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m^2/day), or idarubicin (9-12 mg/m^2/day), or mitoxantrone (8-12 mg/m^2/day) by intravenous infusion for 3 days.
Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (Red blood cells [RBCs] or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad-spectrum antibiotics and/or antifungals.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Guadecitabine	Experimental	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).	Drug: Guadecitabine
Treatment Choice	Active Comparator	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.	Other: Treatment Choice

Name	Type	Description	Arm Group Labels	Other Names
Guadecitabine	Drug		Guadecitabine	SGI-110
Treatment Choice

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the number of days from the day the participant was randomized to the date of death due to any cause. Survival time was censored on the last date the participant is known alive with no event of death. OS time will be estimated using the Kaplan-Meier method.	From randomization up to death (up to approximately 38.6 months)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Transfusion Independence for Any 8 Consecutive Weeks	Transfusion independence rate was calculated as the number of participants with neither RBC nor platelet transfusion for any period of 8 weeks after the initiation of treatment (or cycle 1 day 1 { C1D1} visit date for participants randomized to BSC or randomization date for participants not treated) and up to treatment discontinuation (or 180 days for participants discontinuing the treatment within 6 months), while maintaining haemoglobin (Hgb) ≥8 gram per deciliter (g/dL) and platelets ≥20×10^9/liter (L) divided by the total number of participants included in the efficacy analysis. RBC or Platelet transfusion independence rate was defined similarly as above. Percentage of participants are rounded off to the single decimal point.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult participants ≥18 years of age who are able to understand and comply with study procedures and provide written informed consent before any study-specific procedure.
Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
Performance status (ECOG) of 0-2.
Previously treated MDS or CMML, defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows:
1. Participant received HMA for at least 6 cycles and was still transfusion dependent.
2. Participant received HMA for at least 2 complete cycles and had disease progression prior to Cycle 6 defined as
i. ≥50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadir post-HMA-treatment levels to >5% (for participants with pretreatment or nadir blasts ≤5%) or to >10% (for participants with pretreatment or nadir blasts >5%), and/or ii. Transfusion dependent and ≥2 gram/deciliter (g/dL) reduction of Hgb from pre-HMA-treatment levels.

Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.

Participants must have either:
1. Bone marrow blasts >5% at randomization, OR
2. Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization.
Creatinine clearance or glomerular filtration rate ≥30 milliliter/minute (mL/min) estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment with guadecitabine and for at least 3 months after completing treatment and (b) while receiving treatment with LDAC or IC and for at least 6 months after completing treatment or for the duration specified in local prescribing information, whichever is longer.

Exclusion Criteria:

Participants who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.
Participants who may still be sensitive to repeated treatment with decitabine or azacitidine such as participants who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents.
Prior treatment with guadecitabine.
Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
Treated with any investigational drug within 2 weeks of the first dose of study treatment.
Total serum bilirubin >2.5 × upper limit of normal (ULN) (except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C.
Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen.
Life expectancy of less than one month
Participants with TP53 mutations

Name	Affiliation	Role
Yuri Sano, MD, PhD	Astex Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope		Duarte	California	91010	United States
Desert Hematology Oncology Medical Group, Inc.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Guadecitabine	Participants received Guadecitabine 60 milligrams per square meter (mg/m^2), subcutaneously (SC), on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 2, 2018	Mar 23, 2023

Arm/Group Information

ID	Title	Description
BG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
BG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.
BG002	Total	Total of all reporting groups

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

Overall Survival (OS)

OS was defined as the number of days from the day the participant was randomized to the date of death due to any cause. Survival time was censored on the last date the participant is known alive with no event of death. OS time will be estimated using the Kaplan-Meier method.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Median

95% Confidence Interval

days

From randomization up to death (up to approximately 38.6 months)

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Units	Counts
Participants	OG000277 OG001140

Title

Denominators

Categories

Title	Measurements
	OG000277.0(243.0 to 313.0) OG001252.0(200.0 to 325.0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Stratified Log-rank test		0.6063	OS between Guadecitabine vs Treatment Choice using stratified log-rank test. Due to pre-specified hierarchical testing plan, other endpoints were not evaluated for statistical significance.	Hazard Ratio (HR)	0.94			2-Sided	95	0.74	1.19					Superiority

Secondary

Percentage of Participants With Transfusion Independence for Any 8 Consecutive Weeks

Transfusion independence rate was calculated as the number of participants with neither RBC nor platelet transfusion for any period of 8 weeks after the initiation of treatment (or cycle 1 day 1 { C1D1} visit date for participants randomized to BSC or randomization date for participants not treated) and up to treatment discontinuation (or 180 days for participants discontinuing the treatment within 6 months), while maintaining haemoglobin (Hgb) ≥8 gram per deciliter (g/dL) and platelets ≥20×10^9/liter (L) divided by the total number of participants included in the efficacy analysis. RBC or Platelet transfusion independence rate was defined similarly as above. Percentage of participants are rounded off to the single decimal point.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Number

percentage of participants

Up to approximately 46.6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice

Secondary

Percentage of Participants With Marrow Complete Response (mCR) Along With Transfusion Independence Rate

mCR was defined as per 2006 Myelodysplastic Syndromes International Council for Harmonisation (MDS IWG) criteria as reduction of bone marrow (BM) blasts to ≤5% and decrease by 50% or more with or without normalization of peripheral counts. Transfusion independence rate was calculated as the number of participants with neither RBC nor platelet transfusion for any period of 8 weeks after the initiation of treatment (or C1D1 visit date for participants randomized to BSC or randomization date for participants not treated) and up to treatment discontinuation (or 180 days for participants discontinuing the treatment within 6 months), while maintaining Hgb ≥8 g/dL and platelets ≥20×10^9/L divided by the total number of participants included in the efficacy analysis. The percentage of participants who achieved mCR and transfusion independence simultaneously in the same period were calculated for each group. Percentage of participants are rounded off to the single decimal point.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Number

percentage of participants

Up to approximately 46.6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Secondary

Survival Rate at 1 Year After Randomization

One year survival rate was defined as the percentage of participants that survived at the end of the first year from randomization. Participants who did not have death in record were censored on the last date known to be alive. Percentage of participants are rounded off to the nearest whole number.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization up to 12 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Secondary

Leukemia-free Survival

Leukemia-free survival was defined as the number of days from randomization to the earliest date when participants have bone marrow (BM) or peripheral blood (PB) blasts ≥20%, conversion to acute myeloid leukemia (AML) or death of any cause. Participants with no events in leukemia-free survival were censored on the last date of BM or PB blasts assessment, whichever is later. Survival time will be estimated using the Kaplan-Meier method.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Median

95% Confidence Interval

days

From randomization up to 46.6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Secondary

Number of Days Alive and Out of the Hospital (NDAOH)

The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The NDAOH within first 6 month period was calculated as: NDAOH 6M=180 -total duration of all hospital stays within 180 days from the first treatment -number of death days before Day 180. For participants who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the participant would have died the day after the last contact day.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Median

Full Range

days

Up to 6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Secondary

Disease Response (DR) Rate

DR: Complete Response(CR), Partial Response(PR),Marrow Complete Response(mCR), and Hematological Improvement(HI) including HI with Erythroid (HI-E), HI with Neutrophil (HI-N), or HI with Platelet (HI-P) based on IWG 2006 criteria. CR: BM:≤5% myeloblasts, Peripheral blood: Hgb≥11g/dL, Platelets(PLTs)≥100x10^9/L, Neutrophils≥1.0x10^9/L, Blasts 0%. PR: All CR criteria if abnormal before treatment except BM blasts decreased ≥50% over pretreatment but still>5%, Cellularity, morphology not relevant. HI responses:1) HI-E: Hgb increase ≥1.5g/dL, Relevant reduction of RBC units transfusions by absolute ≥4 RBC transfusions/8 week(wk) compared with pretreatment transfusion number previous 8wk. Only RBC transfusions given for Hgb≤9.0g/dL. 2) HI-P: Absolute increase≥30x10^9/L starting>20x10^9/L PLTs; Increase from<20x10^9/L to>20x10^9/L and by≥100%. 3) HI-N: ≥100% increase, absolute increase>0.5x10^9/L.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment. Participants who had multiple responses of HI (HI-E, HI-N and HI-P) were counted only once while calculating the total HI value in both treatment groups. Percentage of participants are rounded off to the nearest single decimal point.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 46.6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Secondary

Duration of Complete Response (CR)

Duration of complete response (in number of days) was calculated from the first time a CR was observed to the date of the earliest of the following three events: 1) relapse/disease progression, 2) start of alternative therapy (except Hematopoietic Cell Transplant [HCT]) or 3) death. In the absence of any event, the duration of CR was censored at the last available time point (BM assessment, PB assessment, or safety/long-term follow-up visit) at which an event was not observed. Duration of complete response was analysed using a Kaplan-Meier method for participants who achieved a CR during the study. CR: BM: ≤5% myeloblasts (all cell lines normal maturation), Peripheral blood: Hgb ≥11g/dL, PLTs ≥100x10^9/L, Neutrophils ≥1.0x10^9/L, Blasts 0%.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment. Overall number of participants analyzed are the number of participants with CR (responders) only.

Posted

Median

95% Confidence Interval

days

Up to approximately 46.6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice

Secondary

Time to First Response, Complete Response (CR) and Best Response

Time to first response was the time(days) from randomization to first date when any response was achieved. Time to CR was the time(days) from randomization to first date when CR was achieved. Time to best response was the time(days) from randomization to first date when participant's best response (CR,PR,mCR or HI) was achieved. CR:BM:≤5% myeloblasts, Peripheral blood:Hgb≥11g/dL,PLTs≥100x10^9/L,Neutrophils≥1.0x10^9/L,Blasts 0%. PR: All CR criteria except BM blasts decreased≥50% over pretreatment but still >5%,Cellularity,morphology not relevant. mCR: Reduction of BM blasts to≤5%; decrease ≥50% with/without normalization of peripheral counts. HI responses:1)HI-E:Hgb increase≥1.5 g/dL, Relevant reduction of RBC units transfusions by absolute≥4 RBC transfusions/8wk compared with pretreatment transfusion number previous 8wk. 2)HI-P:Absolute increase≥30x10^9/L starting>20x10^9/L PLTs; Increase from≤20 to>20x10^9/L and by≥100% 3)HI-N:≥100% granulocyte increase, absolute increase>0.5x10^9/L.

Posted

Median

Full Range

days

From study Day 1 to the earliest date that a response was first documented (up to approximately 46.6 months)

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Secondary

Number of Red Blood Cell (RBC) and Platelet Transfusions

The total number of RBCs transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit. The mean total number of RBC or platelet units transfused per participant is presented.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment.

Posted

Mean

Standard Deviation

units of transfused RBC or platelet

Up to 6 months

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Secondary

Change From Baseline in Health-related Quality of Life (QOL) By EuroQol 5-level 5-dimension (EQ-5D-5L) Summary Index

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L, first component is a descriptive system five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a second component visual analogue scale (VAS) that measures health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. The health status is converted to an index value using the country-specific weighted scoring algorithm for England. The summary index value for the England ranges from a worst score of -0.281 to a best score of 1. An increase in the EQ-5D-5L total score indicates improvement.

The Efficacy Analysis Set included all participants randomly assigned to the study treatment. Overall number of participants analyzed are the number of participants with data available for analysis. 'Number Analyzed' indicates the number of participants with data available for analysis at the given timepoint. As pre-specified in the statistical analysis plan (SAP), the analysis included only the data collected for each participant during the first 6 months of study participation.

Posted

Mean

Standard Deviation

score on a scale

Baseline to Month 6

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Secondary

Change From Baseline in Health-related QOL: EuroQOL Visual Analogue Scale (EQ-VAS) Score

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. The second component, EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine).

Posted

Mean

Standard Deviation

score on a scale

Baseline to Month 6

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization; results in persistent or significant disability; is congenital anomaly; is suspected transmission of any infectious agent via a medicinal product or is medically important. Treatment emergent AEs which are those with onset date on or after the date of the first dose of study drug on C1D1 until 30 days after the last dose of study treatment, or the start of an alternative anticancer treatment, whichever occurs first.

The Safety Analysis Set included all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

Posted

Count of Participants

Participants

From first dose through end of study (up to approximately 46.6 months)

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Secondary

30-day and 60-day All-cause Mortality

Number of deaths, regardless of cause, within 30 or 60 days from the first study dose divided by the total number of participants included in the Safety Analysis Set. Participants who died within 30 days were also included in the 60-day mortality calculations.

The Safety Analysis Set included all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

Posted

Count of Participants

Participants

From first dose until 60 days after study treatment initiation

ID	Title	Description
OG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).
OG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Guadecitabine	Participants received Guadecitabine 60 mg/m^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).	237	277	216	270	266	270
EG001	Treatment Choice	Participants received one of the three treatment choice options: LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.	122	140	65	122	107	122

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG00080 affected270 at risk EG00119 affected122 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0008 affected270 at risk EG0012 affected122 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0007 affected270 at risk EG0012 affected122 at risk
Febrile Bone Marrow Aplasia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Leukostasis Syndrome	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Splenic Infarction	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Thrombocytopenic Purpura	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Disseminated Intravascular Coagulation	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0006 affected270 at risk EG0011 affected122 at risk
Cardiac Failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0004 affected270 at risk EG0012 affected122 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0010 affected122 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Angina Pectoris	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0011 affected122 at risk
Cardiac Arrest	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Ventricular Extrasystoles	Cardiac disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Gastrointestinal Arteriovenous Malformation	Congenital, familial and genetic disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Deafness	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Lower Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0010 affected122 at risk
Colitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Chronic Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Enterovesical Fistula	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Gastric Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Gastrointestinal Vascular Malformation Haemorrhagic	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Intestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Mouth Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pancreatitis Acute	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Small Intestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Aphthous Ulcer	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Intestinal Obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Megacolon	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Melaena	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Rectal Haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0012 affected122 at risk
Retroperitoneal Haematoma	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment		EG0007 affected270 at risk EG0012 affected122 at risk
General Physical Health Deterioration	General disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0013 affected122 at risk
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Chest Pain	General disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Death	General disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0012 affected122 at risk
Malaise	General disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Systemic Inflammatory Response Syndrome	General disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Bile Duct Stone	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Cholecystitis Acute	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00072 affected270 at risk EG00117 affected122 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00026 affected270 at risk EG0014 affected122 at risk
Septic Shock	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00016 affected270 at risk EG0012 affected122 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00014 affected270 at risk EG0012 affected122 at risk
Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG00011 affected270 at risk EG0011 affected122 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0005 affected270 at risk EG0013 affected122 at risk
Bronchopulmonary Aspergillosis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0004 affected270 at risk EG0010 affected122 at risk
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0004 affected270 at risk EG0011 affected122 at risk
Urosepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0004 affected270 at risk EG0010 affected122 at risk
Anal Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0010 affected122 at risk
Device Related Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Cellulitis Orbital	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Chronic Sinusitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Corynebacterium Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Pseudomonal Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Sinusitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Staphylococcal Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Subcutaneous Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Abscess Jaw	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Anorectal Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Brain Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Clostridial Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Corona Virus Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Endocarditis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Endophthalmitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Enterococcal Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Enterocolitis Infectious	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Fungal Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Furuncle	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Gingivitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Haematoma Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Herpes Virus Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Metapneumovirus Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Mucormycosis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Necrotising Fasciitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Necrotising Soft Tissue Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Otitis Media Acute	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Periorbital Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pneumococcal Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pseudomembranous Colitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pyelonephritis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pyelonephritis Acute	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Sinusitis Fungal	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Soft Tissue Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Staphylococcal Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Streptococcal Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Streptococcal Endocarditis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Streptococcal Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Urinary Tract Infection Staphylococcal	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Vulval Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Wound Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Candida Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Clostridium Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Erysipelas	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Nocardiosis	Infections and infestations	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0011 affected122 at risk
Subarachnoid Haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Acute Haemolytic Transfusion Reaction	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Joint Dislocation	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Ligament Sprain	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Subdural Haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Toxicity To Various Agents	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Lumbar Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Rib Fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Transfusion Reaction	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0012 affected122 at risk
C-Reactive Protein Increased	Investigations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
General Physical Condition Abnormal	Investigations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Troponin Increased	Investigations	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Tumour Lysis Syndrome	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Fistula Inflammation	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Joint Effusion	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Synovial Cyst	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Osteoporotic Fracture	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Metastases To Central Nervous System	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Transitional Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Central Nervous System Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Tumour Associated Fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Haemorrhage Intracranial	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0012 affected122 at risk
Central Nervous System Haemorrhage	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Cerebral Haemorrhage	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Intracranial Haematoma	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Loss Of Consciousness	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Cerebral Infarction	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Sciatica	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Confusional State	Psychiatric disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Organic Brain Syndrome	Psychiatric disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Haematuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0003 affected270 at risk EG0011 affected122 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0012 affected122 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Renal Impairment	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Urinary Retention	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Urinary Tract Pain	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	Number of participants at risk are based on the male population.	EG0001 affected194 at risk EG0010 affected96 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0004 affected270 at risk EG0011 affected122 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0002 affected270 at risk EG0010 affected122 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Pleuritic Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0011 affected122 at risk
Bronchopneumopathy	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Choking	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Pulmonary Mass	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk
Acute Febrile Neutrophilic Dermatosis	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Aortic Aneurysm	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Haematoma	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0012 affected122 at risk
Internal Haemorrhage	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0001 affected270 at risk EG0010 affected122 at risk
Shock Haemorrhagic	Vascular disorders	MedDRA 21.0	Systematic Assessment		EG0000 affected270 at risk EG0011 affected122 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00063 affected270 at risk EG00122 affected122 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00038 affected270 at risk EG0016 affected122 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00032 affected270 at risk EG00112 affected122 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00092 affected270 at risk EG00119 affected122 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00084 affected270 at risk EG00125 affected122 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00027 affected270 at risk EG0016 affected122 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00062 affected270 at risk EG00112 affected122 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00060 affected270 at risk EG00120 affected122 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00016 affected270 at risk EG0014 affected122 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00043 affected270 at risk EG00115 affected122 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00038 affected270 at risk EG0017 affected122 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00029 affected270 at risk EG0017 affected122 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG00053 affected270 at risk EG00112 affected122 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG00059 affected270 at risk EG00111 affected122 at risk
Injection Site Reaction	General disorders	MedDRA 21.0	Systematic Assessment	EG00046 affected270 at risk EG0011 affected122 at risk
Oedema	General disorders	MedDRA 21.0	Systematic Assessment	EG00014 affected270 at risk EG0019 affected122 at risk
Oedema Peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG00042 affected270 at risk EG00114 affected122 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG00060 affected270 at risk EG00124 affected122 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00022 affected270 at risk EG0014 affected122 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00010 affected270 at risk EG0017 affected122 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00040 affected270 at risk EG0018 affected122 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00016 affected270 at risk EG0017 affected122 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00013 affected270 at risk EG0017 affected122 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG00024 affected270 at risk EG0018 affected122 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG00017 affected270 at risk EG0015 affected122 at risk
Transfusion Reaction	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG00017 affected270 at risk EG0013 affected122 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00013 affected270 at risk EG0018 affected122 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00010 affected270 at risk EG0018 affected122 at risk
Blood Creatinine Increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00014 affected270 at risk EG0015 affected122 at risk
Weight Decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00022 affected270 at risk EG0016 affected122 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00049 affected270 at risk EG0015 affected122 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00045 affected270 at risk EG0016 affected122 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00014 affected270 at risk EG0015 affected122 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected270 at risk EG0015 affected122 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00033 affected270 at risk EG0013 affected122 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00017 affected270 at risk EG0012 affected122 at risk
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected270 at risk EG0017 affected122 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected270 at risk EG0018 affected122 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected270 at risk EG0019 affected122 at risk
Insomnia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00031 affected270 at risk EG0015 affected122 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00039 affected270 at risk EG0018 affected122 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00033 affected270 at risk EG00111 affected122 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00044 affected270 at risk EG00121 affected122 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00014 affected270 at risk EG0013 affected122 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00014 affected270 at risk EG0012 affected122 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00024 affected270 at risk EG0012 affected122 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00019 affected270 at risk EG0012 affected122 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00027 affected270 at risk EG0017 affected122 at risk
Haematoma	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected270 at risk EG0015 affected122 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG00017 affected270 at risk EG0013 affected122 at risk

Participants received one of the three treatment choice options:

LDAC 20 mg/m^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice.
Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m^2) by IV infusion for 3 days of each 28-day cycles.
BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals.

Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D054437	Myelodysplastic-Myeloproliferative Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D009190	Myelodysplastic Syndromes
D015477	Leukemia, Myelomonocytic, Chronic