The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

Myelodysplastic Syndrome Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01566695
• Other study ID #: AZA-MDS-003
• Secondary ID: 2012-002471-34
• Status: Completed
• Phase: Phase 3
• Start date: April 26, 2013
• Est. completion date: December 21, 2023

Study information

• Verified date: January 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: December 21, 2023
• Est. primary completion date: January 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older

• Have a documented diagnosis of MDS

• Anemia that requires red blood cell transfusions

• Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Must agree to follow pregnancy precautions as required by protocol.

• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted

Exclusion Criteria:

• Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy

• Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study).

• Prior allogeneic or autologous stem cell transplant

• Eligible for allogenic or autologous stem cell transplant

• History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect

• Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)

• Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization

• Ongoing medically significant adverse events from previous treatment, regardless of the time period

• Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for = 1 week prior to randomization for medical conditions other than MDS)

• Prior history of cancer, other than MDS, unless the subject has been free of the disease for = 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed)

• Significant active cardiac disease within the previous 6 months

• Uncontrolled systemic fungal, bacterial, or viral infection

• Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection

• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding

• Abnormal coagulation parameters

• Abnormal liver function test results

• Abnormal kidney function test results

• Known or suspected hypersensitivity to azacitidine or mannitol

• Any significant medical condition, laboratory abnormality, or psychiatric illness

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome
• Thrombocytopenia

Intervention

Drug:
• Oral Azacitidine
300 mg daily, days 1 to 21 of each 28-day treatment cycle
• Placebo
Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.

Other:
• Best Supportiv Care (BSC)
BSC included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.

Locations

Country	Name	City	State
Australia	Local Institution - 129	Adelaide	South Australia
Australia	Local Institution - 131	Camperdown
Australia	Local Institution - 134	Clayton	Victoria
Australia	Local Institution - 127	Epping, VIC
Australia	Local Institution - 133	Fitzroy
Australia	Local Institution - 132	Frankston	Victoria
Australia	Local Institution - 137	Garran	Australian Capital Territory
Australia	Local Institution - 135	Kogarah
Australia	Local Institution - 130	Malvern
Australia	Local Institution - 126	Milton, Brisbane
Australia	Local Institution - 138	Waratah
Australia	Local Institution - 136	Woolloongabba
Belgium	Local Institution - 203	Brasschaat
Belgium	Local Institution - 200	Brugge
Belgium	Local Institution - 202	Charleroi
Belgium	Local Institution - 201	Leuven
Brazil	Local Institution - 155	Curitiba	Paraná
Brazil	Local Institution - 154	Fortaleza	Ceará
Brazil	Local Institution - 152	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution - 153	Rio De Janeiro
Brazil	Local Institution - 151	Sao Paulo
Canada	Local Institution - 183	Barrie	Ontario
Canada	Local Institution - 182	Edmonton	Alberta
Canada	Local Institution - 180	Hamilton	Ontario
Canada	Local Institution - 177	Montreal	Quebec
Canada	Local Institution - 181	Montreal	Quebec
Canada	Local Institution - 176	Toronto	Ontario
Canada	Local Institution - 179	Toronto	Ontario
Canada	Local Institution - 178	Vancouver	British Columbia
Czechia	Local Institution - 226	Brno	Jihomoravský Kraj
Czechia	Local Institution - 230	Hradec Králové
Czechia	Local Institution - 229	Olomouc
Czechia	Local Institution - 227	Praha
Czechia	Local Institution - 228	Praha
Denmark	Local Institution - 253	Aarhus
Denmark	Local Institution - 252	Odense C
Denmark	Local Institution - 251	Roskilde
Finland	Local Institution - 276	Helsinki
Finland	Local Institution - 277	Turku
France	Local Institution - 305	Lille
France	Local Institution - 304	Marseille Cedex 9
France	Local Institution - 301	Nantes
France	Local Institution - 308	Paris
France	Local Institution - 307	Pierre-Bénite Cedex
France	Local Institution - 302	Rennes Cedex
France	Local Institution - 303	Rouen Cedex
France	Local Institution - 306	Strasbourg
France	Local Institution - 300	Toulouse Cedex 9
France	Local Institution - 309	Tours
Germany	Local Institution - 350	Dresden
Germany	Local Institution - 361	Dresden
Germany	Local Institution - 359	Duesseldorf
Germany	Local Institution - 355	Dusseldorf
Germany	Local Institution - 356	Hamburg
Germany	Local Institution - 353	Keil
Germany	Local Institution - 351	Leipzig
Germany	Local Institution - 352	München
Germany	Local Institution - 357	Tubingen
Germany	Local Institution - 360	Ulm
Greece	Local Institution - 851	Alexandroupolis
Greece	Local Institution - 850	Athens
Greece	Local Institution - 852	Athens
Greece	Local Institution - 855	Athens
Greece	Local Institution - 853	Heraklion	Irakleio
Greece	Local Institution - 854	Patras
Israel	Local Institution - 453	Haifa
Israel	Local Institution - 451	Petach Tikva
Israel	Local Institution - 454	Tel Hashomer
Israel	Local Institution - 452	Tel-Aviv	Tel Aviv
Italy	Local Institution - 482	Alessandria
Italy	Local Institution - 492	Bari
Italy	Local Institution - 489	Bologna
Italy	Local Institution - 494	Cagliari
Italy	Local Institution - 486	Firenze
Italy	Local Institution - 479	Lecce
Italy	Local Institution - 498	Milan
Italy	Local Institution - 488	Milano
Italy	Local Institution - 497	Novara
Italy	Local Institution - 480	Palermo
Italy	Local Institution - 495	Pavia
Italy	Local Institution - 496	Pisa
Italy	Local Institution - 485	Reggio Calabria
Italy	Local Institution - 484	Rionero in Vulture
Italy	Local Institution - 481	Roma
Italy	Local Institution - 487	Roma
Italy	Local Institution - 490	Roma
Italy	Local Institution - 499	Terni
Italy	Local Institution - 477	Torino
Italy	Local Institution - 493	Torrette Di Ancona
Italy	Local Institution - 478	Udine
Italy	Local Institution - 476	Venezia - Mestre
Korea, Republic of	Local Institution - 704	Busan
Korea, Republic of	Local Institution - 703	Daegu
Korea, Republic of	Local Institution - 700	Seoul
Korea, Republic of	Local Institution - 701	Seoul
Korea, Republic of	Local Institution - 702	Seoul
Mexico	Local Institution - 830	Huixquilucan de Degollado
Mexico	Local Institution - 828	Monterrey
Mexico	Local Institution - 829	Monterrey
Mexico	Local Institution - 827	Tlalpan
Netherlands	Local Institution - 528	Amsterdam
Netherlands	Local Institution - 527	Groningen
Netherlands	Local Institution - 526	Nijmegen
Netherlands	Local Institution - 529	Rotterdam
Norway	Local Institution - 552	Førde
Norway	Local Institution - 551	Oslo
Poland	Local Institution - 582	Bydgoszcz
Poland	Local Institution - 576	Gdansk
Poland	Local Institution - 579	Krakow
Poland	Local Institution - 581	Lodz
Poland	Local Institution - 580	Torun
Poland	Local Institution - 577	Warszawa
Poland	Local Institution - 583	Warszawa
Poland	Local Institution - 578	Wroclaw
Portugal	Local Institution - 604	Beja
Portugal	Local Institution - 600	Coimbra
Portugal	Local Institution - 601	Lisboa
Portugal	Local Institution - 603	Lisboa
Portugal	Local Institution - 602	Porto
Spain	Local Institution - 626	Badalona (Barcelona)
Spain	Local Institution - 625	Barcelona
Spain	Local Institution - 635	Barcelona
Spain	Local Institution - 636	Granada
Spain	Local Institution - 629	Madrid
Spain	Local Institution - 631	Madrid
Spain	Local Institution - 634	Madrid
Spain	Local Institution - 632	Malaga
Spain	Local Institution - 628	Oviedo
Spain	Local Institution - 630	Salamanca
Spain	Local Institution - 627	Seville
Spain	Local Institution - 633	Vitoria-Gasteiz, Álava
Sweden	Local Institution - 653	Goeteborg
Sweden	Local Institution - 652	Lund
Sweden	Local Institution - 651	Stockholm
Turkey	Local Institution - 401	Adana
Turkey	Local Institution - 405	Antalya
Turkey	Local Institution - 400	Istanbul
Turkey	Local Institution - 403	Istanbul
Turkey	Local Institution - 404	Mersin
Turkey	Local Institution - 402	Trabzon
United Kingdom	Local Institution - 687	Aberdeen
United Kingdom	Local Institution - 691	Birmingham
United Kingdom	Local Institution - 686	Bristol
United Kingdom	Local Institution - 689	Cambridge
United Kingdom	Local Institution - 678	Cardiff
United Kingdom	Local Institution - 688	Harrow Middlesex
United Kingdom	Local Institution - 692	Hull
United Kingdom	Local Institution - 677	Leicester
United Kingdom	Local Institution - 683	Liverpool
United Kingdom	Local Institution - 676	London
United Kingdom	Local Institution - 684	London
United Kingdom	Local Institution - 679	Manchester
United Kingdom	Local Institution - 681	Nottingham
United Kingdom	Local Institution - 685	Oxford	Oxfordshire
United Kingdom	Local Institution - 690	Sutton in Ashfield
United Kingdom	Local Institution - 680	Wolverhampton
United States	Phoebe Cancer Center of Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Johns Hopkins Medicine	Baltimore	Maryland
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Tower Hematology/Oncology Medical Group and Tower Cancer Research Found	Beverly Hills	California
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Robert H Lurie Comprehensive Cancer Center NW Univ	Chicago	Illinois
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	University Of Illinois At Chicago	Chicago	Illinois
United States	University Hospitals of Cleveland Case Medical Center	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	City Of Hope	Duarte	California
United States	California Cancer Associates for Research and Excellence cCARE	Escondido	California
United States	Brooke Army Medical Center Francis Street Medical Center	Fort Sam Houston	Texas
United States	Marin Oncology Associates	Greenbrae	California
United States	Eastern Institute of Medical Sciences	Greenville	North Carolina
United States	Local Institution - 900	Houston	Texas
United States	Michael Debakey VA Medical Center	Houston	Texas
United States	Millennium Physicians - Oncology	Houston	Texas
United States	Jackson Oncology Associates PLLC	Jackson	Mississippi
United States	Kansas City VA Medical Center University of Kansas Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	University Of Kansas Medical Center	Kansas City	Kansas
United States	UCSD-Thornton Hospital	La Jolla	California
United States	University of Southern California Norris Cancer Center	Los Angeles	California
United States	University of Louisville, J.G. Brown Cancer Center	Louisville	Kentucky
United States	Loyola University Chicago	Maywood	Illinois
United States	Hematology And Oncology Specialists, Llc	Metairie	Louisiana
United States	Yale Cancer Center	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai Medical Center	New York	New York
United States	Weill Cornell Medical College - New York - Presbyterian Hospital	New York	New York
United States	University Of Nebraska Medical Center	Omaha	Nebraska
United States	University of Florida Health Cancer Center at Orlando Health	Orlando	Florida
United States	Penn Medicine: University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest Oncology Hematology	Portland	Oregon
United States	VA Commonwealth University - Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UMASS Memorial Hospital	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Spain,  Sweden,  Turkey,  United Kingdom, 

References & Publications (1)

Garcia-Manero G, Almeida A, Giagounidis A, Platzbecker U, Garcia R, Voso MT, Larsen SR, Valcarcel D, Silverman LR, Skikne B, Santini V. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia. BMC Hematol. 2016 May 3;16:12. doi: 10.1186/s12878-016-0049-5. eCollection 2016. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for = 56 Days	RBC transfusion (tfx) independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 56 days (i.e., day 1 to day 56, day 2 to day 57) were considered as a 56-day RBC transfusion independent responder.	Each participant was assessed for at least 56 days or more; from the date of randomization of study drug up to the data cut-off date of 25 January 2019, approximately 5 months.
Secondary	Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days	Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of = 56 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a = 56 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In the event a participant had more than one =56 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis. Participants who maintained RBC TI through the end of the treatment period were censored at the date of treatment discontinuation, death, or 1 day before the start of the subsequent MDS treatment (if any), whichever occurred first, or the particiapnts latest available assessment date in the database if the treatment was still on-going.	From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days	Time to RBC transfusion independence of = 56 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 56 without any RBC transfusions).	From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks	A participant was considered as a RBC transfusion reduction responder if the participant had at least 4 units reduction in transfusion units over any consecutive 56 days period compared to the baseline transfusion units in 56 days.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence for = 84 Days	RBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 84 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 84 days (i.e., day 1 to day 84, day 2 to day 85) were considered as a 84-day RBC transfusion independent responder.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days	Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of = 84 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a = 84 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In case a participant had more than one =84 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days	Time to RBC transfusion independence of = 84 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 84 without any RBC transfusions).	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria	Erythroid HI-E improvement was defined as a hemoglobin increase of = 1.5 g/dL; or a reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of = 9.0 g/dL on treatment were counted in the RBC transfusion response evaluation.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria	HI-P response was defined according to IWG 2006 criteria (Cheson, 2006) and as: 1. Absolute increase of = 30 X 10^9/L for participants^ starting with > 20 X 10^9/L platelets; 2. Increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-P must have lasted at least 8 weeks.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of = 8 Weeks (56 Days)	Platelet transfusion independence was defined as the absence of any platelet transfusion during any consecutive "rolling" 56 days during the treatment period, (ie, Day 1 to 56, Day 2 to 57, Days 3 to 58, etc.). Participants were considered platelet transfusion dependent at baseline if they had received = 2 platelet transfusions during the 56 days immediately preceding randomization and had no consecutive 28-day period during which no platelet transfusions were administered.	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Time to Platelet Transfusion Independence	Time to platelet transfusion independence was defined as the time between randomization and the first documented date of onset of transfusion independence (ie, Day 1 of 56 without any platelet transfusions).	From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Kaplan-Meier Estimate of Overall Survival (OS)	Overall survial was defined as the time from randomization to death from any cause, and was calculated using randomization date and date of death, or date of last follow-up for censored participants. All subjects were followed until drop out (withdrawal of consent from further data collection or lost to follow-up), death, or study closure. Participants who dropped out or were alive at study closure (or at the time of the interim analysis) had their OS times censored at the time of last contact, as appropriate. Overall survival was assessed as an interim analysis at the time of the primary analysis.	From randomization to death from any cause; up to the data cut-off of date of 25 January 2019; maximum follow-up time for all participants was 67.9 months for the oral azacitidine arm and 64.8 months for placebo arm
Secondary	Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS	Hematologic response was defined as: A complete response (CR): <5% myeloblasts, and normal maturation of all cell lines; Peripheral blood (PB) shows: hemoglobin >10 g/dL, neutrophils =1.0x10^9/L, platelets =100x10^9/dL, blasts (0%); Partial Response (PR): same as CR bone marrow (BM) shows blasts decreased by = 50% over pre-treatment but still > 5%; Cellularity and morphology not relevant; Marrow CR: BM: = 5% myeloblasts and decrease by = 50% over pre-treatment PB; Stable disease (SD): failure to achieve at least PR, but no evidence of progression for > 8 wks; Failure: death during treatment or disease progression; Disease Progression for those with: Less than 5% blasts: = 50% increase in blasts to > 5% blasts; 5%-10% blasts:= 50% increase to > 10% blasts; 10%-20% blasts:= 50% increase to > 20% blasts; 20%-30% blasts = 50% increase to > 30% blasts; Any of the following: = 50% decrease from maximum remission/response in granulocytes or platelets	Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo
Secondary	Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)	Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.	From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group
Secondary	Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML	Time to AML progression was defined as the time from the date of randomization until the date the subject has documented progression to AML. For participants who had progression to AML documented in MLL central lab report, the earliest sample collection date with the diagnosis of "s-AML arising from previous MDS" was used as the date to AML progression.	From randomization of study drug to progression of AML; up to final data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Percentage of Participants With Significant Bleeding Events	Clinically significant bleeding event was defined as: any intracranial or retroperitoneal bleed; bleeding requiring transfusions of > 2 units of blood/blood products; bleeding associated with a decrease in hemoglobin of > 2 g/dL; or bleeding from any site requiring transfusions of > 2 units of blood.	From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAE)	A TEAE was defined as an adverse event that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.; A serious adverse event (SAE) is any: Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.	From first dose of IP up to 28 days after the last dose of IP; up to data cut-off date of 25 Jan 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Secondary	Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6	The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6	The FACT-G and FACT-An score are summed to form the FACT-An total score. The FACT-An Trial Outcome Index (TOI) consists of the summation of a "summary scale" and includes the Physical Well-being, (PWB; 7 items; score range, 0-28), the Functional Well-being (7 items; score range, 0-28) and the Anemia subscale consisting of 20 items on the same five-point scale, with 13 of them measuring fatigue related symptoms (FS) and seven measuring non-FS. The FACT-An TOI has been demonstrated to be a sensitive indicator of clinical outcomes in a number of diseases including MDS. The Fact-TOI score ranges from 0 to 136. Higher scores on all scales of the Fact-An and subscales on the FACT-TOI reflect better quality of life or fewer symptoms.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6	The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire (i.e., the Functional Assessment of Cancer Therapy-General [FACT-G]) The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: Physical Well-being (PWB; 7 items; score range, 0-28),; Social/Family Well-being (SWB; 7 items; score range, 0-28),; Emotional Well-being (EWB; 6 items; score range, 0-24), and; Functional Well-being (7 items; score range, 0-28). The FACT-G is a summation composed of a "summary scale" including the PWB, SWB, EWB and FWB. The FACT-G score range is from 0 to 108. For all summary scales including FACT-G, a higher score indicates better HRQoL or lower level of symptoms.	Baseline to Cycle 6 Day 1
Secondary	Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6	The FACT-G and the anemia subscale (AnS) are summed to form the FACT-An total score and the total score ranges from 0 to 188. The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: Physical Well-being (PWB; 7 items; score range, 0-28),; Social/Family Well-being (SWB; 7 items; score range, 0-28),; Emotional Well-being (EWB; 6 items; score range, 0-24), and; Functional Well-being (7 items; score range, 0-28). The AnS consists of 20 items on the same 5-point scale, with 13 of them measuring fatigue-related symptoms (FS) and 7 measuring non-FS. The AnS and FS scores can range from 0-80 and 0-52, respectively. For all domains and summary subscales, a higher score indicates better HRQoL or lower level of symptoms.	Baseline to Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6	A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.	Cycle 6 Day 1
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 2 Day 1 (C2D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 3 Day 1 (C3D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 4 Day 1 (C4D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 5 Day 1 (C5D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 6 Day 1 (C6 D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to Cycle 7 Day 1 (C7D1)
Secondary	Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5	The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by =2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.	From Baseline to End of Treatment
Secondary	Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6	The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by =1 level], no change, worsened [by =1 level], and missing) from baseline are reported.	From Baseline to Cycle 6 Day 1
Secondary	Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6	The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by =1 level], no change, worsened [by =1 level], and missing) from baseline are reported.	From Baseline to Cycle 6 Day 1
Secondary	Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6	TThe EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by =1 level], no change, worsened [by =1 level], and missing) from baseline are reported.	From Baseline to Cycle 6 Day 1
Secondary	Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6	The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by =1 level], no change, worsened [by =1 level], and missing) from baseline are reported.	From Baseline to Cycle 6 Day 1
Secondary	Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6	The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by =1 level], no change, worsened [by =1 level], and missing) from baseline are reported.	From Baseline to Cycle 6 Day 1
Secondary	Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized During the Treatment Period	The number of reasons for hospitalizations and hospital admissions during the treatment period were monitored and include those associated with: AEs, protocol-driven procedures, transfusions, non-protocol procedures, elective procedures or those associated with social, practical or technical reasons in the absence of AEs. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.	From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Secondary	Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason During the Treatment Period	The total number of days hospitalized due to any reason during the treatment period was monitored. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.	From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Secondary	Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years	The number of days hospitalized per total patient years. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.	From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting