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)

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.

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).

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Oral Azacitidine; Other: Best Supportiv Care (BSC); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Local Institution - 131
  • Epping, VIC, Australia, 3076
    • Local Institution - 127
  • Fitzroy, Australia, 3065
    • Local Institution - 133
  • Kogarah, Australia, 2217
    • Local Institution - 135
  • Malvern, Australia, 3144
    • Local Institution - 130
  • Milton, Brisbane, Australia, 4064
    • Local Institution - 126
  • Waratah, Australia, NSW
    • Local Institution - 138
  • Woolloongabba, Australia, QLD 4102
    • Local Institution - 136
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Local Institution - 137
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Local Institution - 129
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 134
    • Frankston, Victoria, Australia, 3199
      • Local Institution - 132
• Belgium
  • Brasschaat, Belgium, 2930
    • Local Institution - 203
  • Brugge, Belgium, 8000
    • Local Institution - 200
  • Charleroi, Belgium, 6000
    • Local Institution - 202
  • Leuven, Belgium, 3000
    • Local Institution - 201
• Brazil
  • Rio De Janeiro, Brazil, 20231-130
    • Local Institution - 153
  • Sao Paulo, Brazil, 05651-901
    • Local Institution - 151
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430370
      • Local Institution - 154
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Local Institution - 155
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Local Institution - 152
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution - 182
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Local Institution - 178
  • Ontario
    • Barrie, Ontario, Canada, LYM6M2
      • Local Institution - 183
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 180
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 179
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 176
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Local Institution - 181
    • Montreal, Quebec, Canada, H4J 1C5
      • Local Institution - 177
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 230
  • Olomouc, Czechia, 77520
    • Local Institution - 229
  • Praha, Czechia, 128 08
    • Local Institution - 228
  • Praha, Czechia, 128 20
    • Local Institution - 227
  • Jihomoravský Kraj
    • Brno, Jihomoravský Kraj, Czechia, 625 00
      • Local Institution - 226
• Denmark
  • Aarhus, Denmark, 8000
    • Local Institution - 253
  • Odense C, Denmark, 5000
    • Local Institution - 252
  • Roskilde, Denmark, DK-4000
    • Local Institution - 251
• Finland
  • Helsinki, Finland, 00029 HUS
    • Local Institution - 276
  • Turku, Finland, 20521
    • Local Institution - 277
• France
  • Lille, France, 59037
    • Local Institution - 305
  • Marseille Cedex 9, France, 13009
    • Local Institution - 304
  • Nantes, France, 44093
    • Local Institution - 301
  • Paris, France, 7575
    • Local Institution - 308
  • Pierre-Bénite Cedex, France, 69495
    • Local Institution - 307
  • Rennes Cedex, France, 35033
    • Local Institution - 302
  • Rouen Cedex, France, 76038
    • Local Institution - 303
  • Strasbourg, France, 67091
    • Local Institution - 306
  • Toulouse Cedex 9, France, 31059
    • Local Institution - 300
  • Tours, France, 37044
    • Local Institution - 309
• Germany
  • Dresden, Germany, 01307
    • Local Institution - 350
  • Dresden, Germany, 01307
    • Local Institution - 361
  • Duesseldorf, Germany, 40479
    • Local Institution - 359
  • Dusseldorf, Germany, 40225
    • Local Institution - 355
  • Hamburg, Germany, D-20099
    • Local Institution - 356
  • Keil, Germany, 24105
    • Local Institution - 353
  • Leipzig, Germany, 04103
    • Local Institution - 351
  • München, Germany, 81675
    • Local Institution - 352
  • Tubingen, Germany, 72076
    • Local Institution - 357
  • Ulm, Germany, 89081
    • Local Institution - 360
• Greece
  • Alexandroupolis, Greece, 68100
    • Local Institution - 851
  • Athens, Greece, 10676
    • Local Institution - 852
  • Athens, Greece, 115 27
    • Local Institution - 855
  • Athens, Greece, 124 62
    • Local Institution - 850
  • Patras, Greece, 26500
    • Local Institution - 854
  • Irakleio
    • Heraklion, Irakleio, Greece, 71110
      • Local Institution - 853
• Israel
  • Haifa, Israel, 31096
    • Local Institution - 453
  • Petach Tikva, Israel, 49100
    • Local Institution - 451
  • Tel Hashomer, Israel, 52621
    • Local Institution - 454
  • Tel Aviv
    • Tel-Aviv, Tel Aviv, Israel, 64239
      • Local Institution - 452
• Italy
  • Alessandria, Italy, 15121
    • Local Institution - 482
  • Bari, Italy, 70124
    • Local Institution - 492
  • Bologna, Italy, 40138
    • Local Institution - 489
  • Cagliari, Italy, 09121
    • Local Institution - 494
  • Firenze, Italy, 50129
    • Local Institution - 486
  • Lecce, Italy, 73100
    • Local Institution - 479
  • Milan, Italy, 20089
    • Local Institution - 498
  • Milano, Italy, 20122
    • Local Institution - 488
  • Novara, Italy, 28100
    • Local Institution - 497
  • Palermo, Italy, 90146
    • Local Institution - 480
  • Pavia, Italy, 27100
    • Local Institution - 495
  • Pisa, Italy, 56126
    • Local Institution - 496
  • Reggio Calabria, Italy, 89133
    • Local Institution - 485
  • Rionero in Vulture, Italy, 85028
    • Local Institution - 484
  • Roma, Italy, 00133
    • Local Institution - 487
  • Roma, Italy, 00161
    • Local Institution - 490
  • Roma, Italy, 00168
    • Local Institution - 481
  • Terni, Italy, 05100
    • Local Institution - 499
  • Torino, Italy, 10126
    • Local Institution - 477
  • Torrette Di Ancona, Italy, 60020
    • Local Institution - 493
  • Udine, Italy, 33100
    • Local Institution - 478
  • Venezia - Mestre, Italy, 30174
    • Local Institution - 476
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Local Institution - 704
  • Daegu, Korea, Republic of, 700-721
    • Local Institution - 703
  • Seoul, Korea, Republic of, 120-752
    • Local Institution - 702
  • Seoul, Korea, Republic of, 06591
    • Local Institution - 701
  • Seoul, Korea, Republic of, 135-710
    • Local Institution - 700
• Mexico
  • Huixquilucan de Degollado, Mexico, 52763
    • Local Institution - 830
  • Monterrey, Mexico, 64460
    • Local Institution - 828
  • Monterrey, Mexico, 64710
    • Local Institution - 829
  • Tlalpan, Mexico, 14080
    • Local Institution - 827
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 528
  • Groningen, Netherlands, 9713 GZ
    • Local Institution - 527
  • Nijmegen, Netherlands, 6500 HB
    • Local Institution - 526
  • Rotterdam, Netherlands, 3075 EA
    • Local Institution - 529
• Norway
  • Førde, Norway, 6807
    • Local Institution - 552
  • Oslo, Norway, N-0027
    • Local Institution - 551
• Poland
  • Bydgoszcz, Poland, 85-168
    • Local Institution - 582
  • Gdansk, Poland, 80-952
    • Local Institution - 576
  • Krakow, Poland, 31-501
    • Local Institution - 579
  • Lodz, Poland, 93-510
    • Local Institution - 581
  • Torun, Poland, 87-100
    • Local Institution - 580
  • Warszawa, Poland, 02-097
    • Local Institution - 583
  • Warszawa, Poland, 02-776
    • Local Institution - 577
  • Wroclaw, Poland, 50-367
    • Local Institution - 578
• Portugal
  • Beja, Portugal, 7801-849
    • Local Institution - 604
  • Coimbra, Portugal, 3000-075
    • Local Institution - 600
  • Lisboa, Portugal, 1099-023
    • Local Institution - 601
  • Lisboa, Portugal, 1150-314
    • Local Institution - 603
  • Porto, Portugal, 4200-072
    • Local Institution - 602
• Spain
  • Badalona (Barcelona), Spain, 8916
    • Local Institution - 626
  • Barcelona, Spain, 08025
    • Local Institution - 635
  • Barcelona, Spain, 8035
    • Local Institution - 625
  • Granada, Spain, 18014
    • Local Institution - 636
  • Madrid, Spain, 28009
    • Local Institution - 629
  • Madrid, Spain, 28034
    • Local Institution - 634
  • Madrid, Spain, 28046
    • Local Institution - 631
  • Malaga, Spain, 29010
    • Local Institution - 632
  • Oviedo, Spain, 33006
    • Local Institution - 628
  • Salamanca, Spain, 37007
    • Local Institution - 630
  • Seville, Spain, 41013
    • Local Institution - 627
  • Vitoria-Gasteiz, Álava, Spain, 1009
    • Local Institution - 633
• Sweden
  • Goeteborg, Sweden, 413 45
    • Local Institution - 653
  • Lund, Sweden, 222 41
    • Local Institution - 652
  • Stockholm, Sweden, 14186
    • Local Institution - 651
• Turkey
  • Adana, Turkey, 01250
    • Local Institution - 401
  • Antalya, Turkey, 07100
    • Local Institution - 405
  • Istanbul, Turkey, 34098
    • Local Institution - 403
  • Istanbul, Turkey, 34390
    • Local Institution - 400
  • Mersin, Turkey, 33343
    • Local Institution - 404
  • Trabzon, Turkey, 61080
    • Local Institution - 402
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Local Institution - 687
  • Birmingham, United Kingdom, B9 5SS
    • Local Institution - 691
  • Bristol, United Kingdom, BS2 8ED
    • Local Institution - 686
  • Cambridge, United Kingdom, CB2 0QQ
    • Local Institution - 689
  • Cardiff, United Kingdom, CF14 4XW
    • Local Institution - 678
  • Harrow Middlesex, United Kingdom, HA1 3UJ
    • Local Institution - 688
  • Hull, United Kingdom, HU16 5JQ
    • Local Institution - 692
  • Leicester, United Kingdom, LE1 5WW
    • Local Institution - 677
  • Liverpool, United Kingdom, L7 8XP
    • Local Institution - 683
  • London, United Kingdom, EC1A 7BE
    • Local Institution - 676
  • London, United Kingdom, SE1 9RT
    • Local Institution - 684
  • Manchester, United Kingdom, M13 9WL
    • Local Institution - 679
  • Nottingham, United Kingdom, NG5 1PB
    • Local Institution - 681
  • Sutton in Ashfield, United Kingdom, NG17 4JL
    • Local Institution - 690
  • Wolverhampton, United Kingdom, WV10 0QP
    • Local Institution - 680
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Local Institution - 685
• United States
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Comprehensive Cancer Center
    • Beverly Hills, California, United States, 90211
      • Tower Hematology/Oncology Medical Group and Tower Cancer Research Found
    • Duarte, California, United States, 91010-301
      • City of Hope
    • Escondido, California, United States, 92025
      • California Cancer Associates for Research and Excellence cCARE
    • Greenbrae, California, United States, 94904-2007
      • Marin Oncology Associates
    • La Jolla, California, United States, 92093-0943
      • UCSD-Thornton Hospital
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • University of Florida Health Cancer Center at Orlando Health
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Cancer Center of Phoebe Putney Memorial Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Robert H Lurie Comprehensive Cancer Center NW Univ
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160-7233
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, J.G. Brown Cancer Center
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Hematology And Oncology Specialists, Llc
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Medicine
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates PLLC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center University of Kansas Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - New York - Presbyterian Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Greenville, North Carolina, United States, 27834
      • Eastern Institute of Medical Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44106-5000
      • University Hospitals of Cleveland Case Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest Oncology Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine: University of Pennsylvania Health System
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Cancer Institute
  • Texas
    • Fort Sam Houston, Texas, United States, 78235-8200
      • Brooke Army Medical Center Francis Street Medical Center
    • Houston, Texas, United States, 77030
      • Michael DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • Local Institution - 900
    • Houston, Texas, United States, 77090
      • Millennium Physicians - Oncology
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • VA Commonwealth University - Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-4417
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188-5099
      • Waukesha Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Azacitidine; Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.	Drug: Oral Azacitidine; 300 mg daily, days 1 to 21 of each 28-day treatment cycle; Other Names: CC-486; 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.
Placebo Comparator: Placebo; Arm 2: Identically matching placebo tablets plus best supportive care on days 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.; Drug: Placebo; Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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% blasts5%-10% blasts:≥ 50% increase to > 10% blasts10%-20% blasts:≥ 50% increase to > 20% blasts20%-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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• Garcia-Manero G, Santini V, Almeida A, Platzbecker U, Jonasova A, Silverman LR, Falantes J, Reda G, Buccisano F, Fenaux P, Buckstein R, Diez Campelo M, Larsen S, Valcarcel D, Vyas P, Giai V, Oliva EN, Shortt J, Niederwieser D, Mittelman M, Fianchi L, La Torre I, Zhong J, Laille E, Lopes de Menezes D, Skikne B, Beach CL, Giagounidis A. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. J Clin Oncol. 2021 May 1;39(13):1426-1436. doi: 10.1200/JCO.20.02619. Epub 2021 Mar 25.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2013
• Primary Completion (Actual): January 25, 2019
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: March 28, 2012
• First Posted (Estimated): March 29, 2012

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Blood Platelet Disorders; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Thrombocytopenia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: AZA-MDS-003; 2012-002471-34 (EudraCT Number)