Clinical Trial Results:
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
Summary
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EudraCT number |
2012-002471-34 |
Trial protocol |
BE NO SE ES CZ PT LT IT NL GB DE FI DK FR GR |
Global end of trial date |
21 Dec 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jan 2025
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First version publication date |
01 Jan 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AZA-MDS-003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussee de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Feb 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Dec 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to evaluate RBC transfusion independence in the 2 treatment arms (oral azacitidine plus best supportive care versus placebo plus best supportive care) in subjects with RBC transfusion-dependent anemia and thrombocytopenia due to IPSS lower-risk MDS.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Apr 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 18
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
Canada: 11
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Country: Number of subjects enrolled |
Czechia: 10
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Country: Number of subjects enrolled |
Finland: 2
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
Germany: 27
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Country: Number of subjects enrolled |
Greece: 3
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Country: Number of subjects enrolled |
Israel: 4
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Country: Number of subjects enrolled |
Italy: 46
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Mexico: 3
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Poland: 7
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Country: Number of subjects enrolled |
Portugal: 11
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Country: Number of subjects enrolled |
Spain: 24
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Country: Number of subjects enrolled |
Sweden: 3
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Country: Number of subjects enrolled |
Türkiye: 1
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Country: Number of subjects enrolled |
United Kingdom: 18
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Country: Number of subjects enrolled |
United States: 12
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Worldwide total number of subjects |
216
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EEA total number of subjects |
148
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
172
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85 years and over |
14
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Recruitment
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Recruitment details |
Participants were randomized at 101 sites globally. The sites were located in: Europe (76), North America (13), Asia/Pacific (10), and Latin America (2). Results are reported as of the data cut-off date of 25 January 2019. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participants were stratified by: average baseline (BL) Red Blood Cell (RBC) transfusion requirement (≤ 4 units versus > 4 units of RBC per 28 days), BL platelet transfusion status (dependent or independent), country of enrollment and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 to 1 versus 2). | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Oral Azacitidine Plus Best Supportive Care | ||||||||||||||||||||||||||||||
Arm description |
Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which 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. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Azacitidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle
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Arm title
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Placebo Plus Best Supportive Care | ||||||||||||||||||||||||||||||
Arm description |
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received placebo tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle
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Baseline characteristics reporting groups
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Reporting group title |
Oral Azacitidine Plus Best Supportive Care
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Reporting group description |
Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Plus Best Supportive Care
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Reporting group description |
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Oral Azacitidine Plus Best Supportive Care
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Reporting group description |
Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which 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. | ||
Reporting group title |
Placebo Plus Best Supportive Care
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Reporting group description |
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections. |
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End point title |
Percentage of Participants who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days | ||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
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.
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Statistical analysis title |
RBC Transfusion Independence for ≥ 56 Days | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.0005 [1] | ||||||||||||
Method |
Stratified Mantel-Haenszel Chi-squared | ||||||||||||
Parameter type |
Rate Difference | ||||||||||||
Point estimate |
18.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
8.3 | ||||||||||||
upper limit |
29.6 | ||||||||||||
Notes [1] - 2 sided |
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End point title |
Duration of RBC Transfusion Independence Among Participants who Achieved RBC Transfusion Independence for at Least 56 Days | ||||||||||||
End point description |
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.
"99999"=N/A
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End point type |
Secondary
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End point timeframe |
From the date of randomization of study drug up to
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Statistical analysis title |
Duration of RBC Transfusion Independence | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.0005 | ||||||||||||
Method |
Two-sided Unstratified Log Rank Test | ||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||
Point estimate |
3.34
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.64 | ||||||||||||
upper limit |
6.79 |
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End point title |
Time to RBC Transfusion Independence for at Least 56 Days Among Participants who Achieved RBC Transfusion Independence for at Least 56 Days | ||||||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
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
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No statistical analyses for this end point |
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End point title |
Duration of RBC Transfusion Reduction for Participants who Achieved RBC Transfusion Reduction of at Least 4 units of RBCs for at Least 8 Weeks | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
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
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No statistical analyses for this end point |
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End point title |
Percentage of Participants who Achieved Red Blood Cell Transfusion Independence for ≥ 84 days | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
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
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Statistical analysis title |
RBC Transfusion Independence for ≥ 84 days | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.0001 [2] | ||||||||||||
Method |
Stratified Mantel-Haenszel; Chi-squared | ||||||||||||
Parameter type |
Rate Difference | ||||||||||||
Point estimate |
21.6
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
11.9 | ||||||||||||
upper limit |
31.3 | ||||||||||||
Notes [2] - 2 sided |
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End point title |
Duration of RBC Transfusion Independence Among Participants who Achieved RBC Transfusion Independence for at Least 84 Days | ||||||||||||
End point description |
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.
"99999"=N/A
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End point type |
Secondary
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End point timeframe |
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
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Statistical analysis title |
Duration of RBC Transfusion Independence | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
37
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
= 0.4347 | ||||||||||||
Method |
Two-Sided Unstratified Log Rank Test | ||||||||||||
Confidence interval |
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End point title |
Time to RBC Transfusion Independence for at Least 84 Days Among Participants who Achieved RBC Transfusion Independence for at Least 84 Days | ||||||||||||
End point description |
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 (i.e., Day 1 of 84 without any RBC transfusions).
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End point type |
Secondary
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End point timeframe |
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
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria | |||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
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
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Statistical analysis title |
Erythroid Hematological Improvement (HI-E) | |||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
[3] | |||||||||||||||||||||
P-value |
= 0.1467 | |||||||||||||||||||||
Method |
Stratified Mantel-Haenszel. Chi-squared | |||||||||||||||||||||
Parameter type |
Rate Difference | |||||||||||||||||||||
Point estimate |
10.9
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Confidence interval |
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level |
95% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
-2 | |||||||||||||||||||||
upper limit |
23.7 | |||||||||||||||||||||
Notes [3] - HI-E |
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Statistical analysis title |
Erythroid Hematological Improvement (HI-E) | |||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
[4] | |||||||||||||||||||||
P-value |
= 0.1431 | |||||||||||||||||||||
Method |
Stratified Mantel-Haenszel. Chi-squared | |||||||||||||||||||||
Parameter type |
Rate Difference | |||||||||||||||||||||
Point estimate |
10.9
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Confidence interval |
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level |
95% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
-1.9 | |||||||||||||||||||||
upper limit |
23.6 | |||||||||||||||||||||
Notes [4] - RBC Transfusion Reduction |
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Statistical analysis title |
Erythroid Hematological Improvement (HI-E) | |||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||
Number of subjects included in analysis |
216
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
[5] | |||||||||||||||||||||
P-value |
= 0.0002 | |||||||||||||||||||||
Method |
Stratified Mantel-Haenszel. Chi-squared | |||||||||||||||||||||
Parameter type |
Rate Diffrence | |||||||||||||||||||||
Point estimate |
17.9
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
8.8 | |||||||||||||||||||||
upper limit |
26.9 | |||||||||||||||||||||
Notes [5] - ≥ 1.5 g/dL Hemoglobin Increase |
|
|||||||||||||
End point title |
Percentage of Participants with a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
HI-P | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
216
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.0007 | ||||||||||||
Method |
Stratified Mantel-Haenszel. Chi-squared | ||||||||||||
Parameter type |
Rate Difference | ||||||||||||
Point estimate |
17
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
7.5 | ||||||||||||
upper limit |
26.4 |
|
|||||||||||||
End point title |
Percentage of Participants who Achieved Platelet Transfusion Independence with a Duration of ≥ 8 weeks (56 days) | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Platelet Transfusion Independence | ||||||||||||
End point description |
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).
"99999"=N/A
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Overall Survival (OS) | ||||||||||||
End point description |
Overall survival 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From randomization up to death from any cause; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
OS | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
216
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.6257 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Cox proportional hazard | ||||||||||||
Point estimate |
1.08
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.79 | ||||||||||||
upper limit |
1.49 |
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with a Hematologic Response According to the 2006 IWG Criteria for MDS | ||||||||||||||||||||||||||||||
End point description |
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
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants who Progressed to Acute Myeloid Leukemia (AML) | ||||||||||||
End point description |
Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Progression to Acute Myeloid Leukemia (AML) Among Participants who Progressed to AML | ||||||||||||
End point description |
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.
"99999"=N/A
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From randomization of study drug to progression of AML; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants with Significant Bleeding Events | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment Emergent Adverse Events (TEAE) | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From first dose of IP up to 28 days after the last dose of IP; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
FACT-An | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.214 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Social Well-Being | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.446 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Emotional Well-Being | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.248 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Functional Well-Being | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.058 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Anemia Subscale within FACT-An Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Anemia | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.13 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Fatigue-Related Subscale within the FACT-An Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Fatigue | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.123 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
FACT-An TOI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.069 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
FACT-G | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.078 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Anemia Total Score | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
91
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.073 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.56 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Raatio | ||||||||||||
Point estimate |
0.77
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.54 | ||||||||||||
upper limit |
1.3 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Social Well-Being | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.48 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Raatio | ||||||||||||
Point estimate |
0.72
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.29 | ||||||||||||
upper limit |
1.78 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.197 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
1.67
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.76 | ||||||||||||
upper limit |
3.65 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.121 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
2.14
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.82 | ||||||||||||
upper limit |
5.57 |
|
|||||||||||||
End point title |
Percentage of Participants with a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain within the FACT-An Instrument at Cycle 6 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.075 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.93 | ||||||||||||
upper limit |
4.3 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.222 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
1.58
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.76 | ||||||||||||
upper limit |
3.29 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.249 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
1.65
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.71 | ||||||||||||
upper limit |
3.83 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.082 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
2.03
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.92 | ||||||||||||
upper limit |
4.48 |
|
|||||||||||||
End point title |
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 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Cycle 6 Day 1
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI | ||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
= 0.153 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Common Odds Ratio | ||||||||||||
Point estimate |
1.86
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.79 | ||||||||||||
upper limit |
4.34 |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 2 Day 1 (C2D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 2 Day 1 (C2D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 3 Day 1 (C3D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 3 Day 1 (C3D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Responses to the Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.046 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 4 Day 1 (C4D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 4 Day 1 (C4D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.134 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 5 Day 1 (C5D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 5 Day 1 (C5D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.324 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 6 Day 1 (C6 D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1 (C6 D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.442 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 7 Day 1 (C7D1) | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 7 Day 1 (C7D1)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.063 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Change from Baseline in Responses to the Fact-Anemia Item GP-5 - End of Treatment | |||||||||||||||||||||||||||
End point description |
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.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
From Baseline to End of Treatment
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Statistical analysis title |
Fact-Anemia Item GP-5 | |||||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
||||||||||||||||||||||||||||
P-value |
= 0.198 | |||||||||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
EQ-5D-3L | ||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.972 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
European Quality of Life | ||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.601 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
EQ-5D-3L | ||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.07 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
EQ-5D-3L | ||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.436 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||
End point title |
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 | ||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Baseline to Cycle 6 Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
EQ-5D-3L | ||||||||||||||||||||||||
Comparison groups |
Placebo Plus Best Supportive Care v Oral Azacitidine Plus Best Supportive Care
|
||||||||||||||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
|||||||||||||||||||||||||
P-value |
= 0.683 | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||||||||
End point title |
Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized During the Treatment Period | ||||||||||||||||||||||||||||||
End point description |
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.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to any Reason During the Treatment Period | |||||||||
End point description |
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.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
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
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Participants were assessed for all-cause mortality from their randomization to study completion, (up to approximately 10 years). SAEs and Other AEs were assessed from first dose to 28 days following last dose (up to approximately 6 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
CC-486
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Reporting group description |
Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Feb 2018 |
The duration of the study and enrollment period was extended due to slow enrollment; Based on Food and Drug Administration (FDA) recommendation, for subjects in Cycle 1 or 2 as of 31 Jan 2018, dose schedule was reduced to 14 days; Based on DMC recommendation to enhance hematotoxicity monitoring, the following information was added to Section 8.2.4. Dose Modifications: “Any subject who experiences febrile neutropenia ≥ Grade 3 will have IP held until fever has resolved; must be afebrile for 3 days before re-starting study drug. Administration of antibiotic, antiviral and antifungal therapy is strongly recommended"; Based on DMC recommendation, to enhance hematotoxicity monitoring, dose
modification for neutropenia Grade 4 was updated; Based on DMC recommendation, to enhance hematotoxicity monitoring for Febrile Neutropenia, the following wording “Secondary prophylaxis with G-CSF may be considered” was changed to “Secondary prophylaxis with G-CSF is strongly recommended"; Based on DMC recommendation, to enhance hematotoxicity monitoring, Section 8.2.5. Re-treatment Criteria was updated to reflect that for subjects that experience hematotoxicity (absolute neutrophil count [ANC] or platelet drop to Grade 4, or 50% drop within Grade 4), hematologic recovery is required before starting the next cycle at Day 28. Hematology recovery is defined and a decision tree for hematologic recovery presents the rules in a friendly manner; Based on DMC recommendation, to enhance hematotoxicity monitoring, the following sentences were added: “Consider platelet transfusion if platelet counts are < 25 x 109/L; Based on DMC recommendation, add information to enhance hematotoxicity monitoring. |
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06 Aug 2018 |
This protocol is being amended to address the sponsor’s decision to close enrollment into the study and revise sample size. |
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28 Nov 2018 |
This protocol was amended to change the primary endpoint to RBC transfusion independence with duration ≥ 56 days (8 weeks) and to add an extension phase of CC-486 treatment once the trial is unblinded. |
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24 May 2022 |
Updated contact details for the Medical Monitor of the study; Therapeutic Area Head and their title were updated; New section added; Survival follow-up (FU) was updated by reducing the duration of survival FU to 35 days (± 7 days)
after treatment discontinuation. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |