RENAL: Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT00652626
Collaborator
(none)
31
Enrollment
11
Locations
5
Arms
44
Actual Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate three things. The first being whether azacitidine is absorbed in the body at the same rate or proportion for different concentrations. The second is to determine the effect renal impairment has or does not have on the absorption of azacitidine. The third is to determine if azacitidine is safe and well tolerated in patients with renal function impairment.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1, Open-Label, Multi-Center, Parallel Group Study to the Pharmacokinetics and Safety of Subcutaneous Azacitidine in Adult Cancer Patients With and Without Impaired Renal Function
Actual Study Start Date :
Nov 1, 2008
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Jul 1, 2012

Arms and Interventions

ArmIntervention/Treatment
Experimental: Azacitidine 25 mg/m^2

Participants with normal renal function received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.

Drug: azacitidine
Other Names:
  • Vidaza
  • Experimental: Azacitidine 50 mg/m^2

    Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.

    Drug: azacitidine
    Other Names:
  • Vidaza
  • Experimental: Azacitidine 75 mg/m^2

    Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.

    Drug: azacitidine
    Other Names:
  • Vidaza
  • Experimental: Azacitidine 100 mg/m^2

    Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.

    Drug: azacitidine
    Other Names:
  • Vidaza
  • Experimental: Severe RI: azacitidine 75 mg/m^2

    Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.

    Drug: azacitidine
    Other Names:
  • Vidaza
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.

    2. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.

    3. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine after a single dose, calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation: AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.

    4. Maximum Plasma Concentration of Azacitidine (Cmax) [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The maximum observed plasma concentration of azacitidine after a single dose on Day 1.

    5. Time to Maximum Plasma Concentration of Azacitidine (Tmax) [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The time to first maximum observed plasma concentration of azacitidine after a single dose on Day 1.

    6. Terminal Phase Half-life of Azacitidine (t½) [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The terminal phase half-life of azacitidine after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.

    7. Apparent Total Clearance of Azacitidine (CL/F) [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The apparent total clearance of azacitidine after a single dose on Day 1, calculated as Dose/AUC0-inf.

    8. Apparent Volume of Distribution of Azacitidine (Vz/F) [Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The apparent volume of distribution of azacitidine after a single dose on Day 1, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz)

    9. Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The effect of renal impairment on azacitidine pharmacokinetics was analyzed by comparing PK parameters obtained on Days 1 and 5 from participants with severe renal impairment and those with normal renal function. Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule.

    10. Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule for participants with normal renal function and for participants with severe renal impairment.

    11. Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine, after a single dose (Day 1) and multiple doses (Day 5), calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation: AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.

    12. Maximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and for participants with severe renal impairment.

    13. Time to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The time to first maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment.

    14. Terminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The terminal phase half-life of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.

    15. Apparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The apparent total clearance of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated as Dose/AUC0-inf.

    16. Apparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine [Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose]

      The apparent volume of distribution of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz).

    17. Number of Participants With Adverse Events (AEs) [Initial treatment phase: Days 1-11 for participants who received a single dose; Days 1-29 for participants who received multiple doses. Extension treatment period: From the date of first dose until 28 days after the date of last dose (up to 7 months).]

      A serious adverse event is one that at any dose of the study drug or at any time during the period of observation: Results in death; Is life threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is medically important. The Investigator assessed each AE for potential causal relationship between the event and study drug. The intensity of adverse changes in physical signs or symptoms was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of one of the following:

    • MDS according to the French-American-British (FAB) classification system: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMML); or

    • Acute myelogenous leukemia (AML) in remission,

    • Malignant solid tumor,

    • Multiple myeloma (MM),

    • Non-Hodgkin lymphoma (NHL), or

    • Hodgkin lymphoma (HD)

    • Patients with a history of treated brain metastases should be clinically stable for greater than 4 weeks prior to signing the informed consent form and off glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks

    • Be capable of giving informed consent

    • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

    • Have a life expectancy ≥ 3 months

    • Have stable renal function for at least 2 months

    • Have average calculated creatinine clearance of:

    • 80 mL/min/1.73m^2 for Cohorts 1, 2, 3, and 4

    • <30 mL/min/1.73m^2 for Cohort 5 - Severe renal impairment,

    • 50-80 mL/min/1.73m^2 for Cohort 6 - Mild renal impairment,

    • 30 to <50 mL/min/1.73m^2 for Cohort 7 - Moderate renal impairment

    • Have organ and marrow function at the screening and pre-dose visits as defined below:

    • Hemoglobin ≥8 g/dL,

    • Absolute neutrophil count ≥0.75 x 10^3/µL,

    • Platelets ≥30 x 10^3/µL,

    • Total bilirubin ≤1.5 times the upper limit of normal (ULN),

    • Aspartate aminotransferase (AST) ≤2 times the ULN, and

    • Alanine transaminase (ALT) ≤2 times the ULN;

    • Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as determined by the Investigator, at screening

    • Have serum bicarbonate:

    • 20 mEq/L for patients with normal renal function (cohorts 1, 2, 3 and 4),

    • 16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)

    • Women of childbearing potential may participate, providing are not pregnant and agree to use at least 2 effective contraceptive methods throughout the study

    • Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and to avoid fathering a child for 6 months following the date of the last dose of study medication

    • Be a nonsmoker or must not have smoked for at least 30 days before the screening visit and agree to abstain from smoking during study participation

    Exclusion Criteria:
    • Women who are pregnant or nursing;

    • Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin

    1. prior to signing informed consent
    • Have been treated with an investigational agent within 4 weeks prior to signing the informed consent form

    • Have ongoing clinically significant adverse event(s) due to chemotherapy, radiotherapy or investigational agents administered more than 4 weeks prior to signing the informed consent as determined by the Investigator

    • Have known or suspected hypersensitivity to azacitidine or mannitol

    • Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia

    • Have low blood pressure (supine blood pressure <90/60 mmHg)

    • Have human immunodeficiency virus (HIV), or active hepatitis virus B or C

    • Have advanced malignant hepatic tumors

    • Have end stage renal disease requiring dialysis

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Sutter East Bay HospitalsBerkeleyCaliforniaUnited States94704
    2Palm Springs Research InstituteHialeahFloridaUnited States33012
    3MCG Cancer CenterAugustaGeorgiaUnited States30912
    4Joliet Oncology-Hematology Associates, Ltd.JolietIllinoisUnited States60435
    5University of Kentucky-Markey Cancer Center Clinical Research OrganizationLexingtonKentuckyUnited States40536
    6Nevada Cancer InstituteLas VegasNevadaUnited States89135
    7Montefiore Medical CenterBronxNew YorkUnited States10461
    8Mid Dakota Clinical P.C. - Cancer Treatment and Research CenterBismarckNorth DakotaUnited States58501
    9Gabrail Cancer CenterCantonOhioUnited States44718
    10Pharma ResourceEast ProvidenceRhode IslandUnited States02915
    11Cancer Therapy and Research CenterSan AntonioTexasUnited States78229

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Jay Backstrom, MD, Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00652626
    Other Study ID Numbers:
    • AZA PH US 2007 PK006
    First Posted:
    Apr 4, 2008
    Last Update Posted:
    Nov 19, 2019
    Last Verified:
    Nov 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function (RF) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.Participants with severe renal impairment (RI) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.
    Period Title: Initial Treatment Phase
    STARTED5576800
    Received Study Drug5565600
    COMPLETED5565500
    NOT COMPLETED0011300
    Period Title: Initial Treatment Phase
    STARTED00000144
    COMPLETED0000021
    NOT COMPLETED00000123

    Baseline Characteristics

    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RITotal
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function (RF) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.Participants with severe renal impairment (RI) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.Total of all reporting groups
    Overall Participants5565614445
    Age (years) [Mean (Standard Deviation) ]
    Initial Treatment Period
    67.6
    (3.78)
    64.6
    (9.63)
    53.5
    (10.19)
    57.0
    (12.02)
    74.5
    (12.58)
    NA
    (NA)
    NA
    (NA)
    63.5
    (12.32)
    Extension Treatment Period
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    60.6
    (9.52)
    68.8
    (11.0)
    62.4
    (10.15)
    Sex/Gender, Customized (participants) [Number]
    Female
    3
    60%
    3
    60%
    3
    50%
    4
    80%
    3
    50%
    0
    0%
    0
    0%
    16
    35.6%
    Male
    2
    40%
    2
    40%
    3
    50%
    1
    20%
    3
    50%
    0
    0%
    0
    0%
    11
    24.4%
    Race/Ethnicity, Customized (participants) [Number]
    Black
    1
    20%
    2
    40%
    1
    16.7%
    2
    40%
    2
    33.3%
    0
    0%
    0
    0%
    8
    17.8%
    White
    4
    80%
    3
    60%
    5
    83.3%
    3
    60%
    4
    66.7%
    0
    0%
    0
    0%
    19
    42.2%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%
    5
    100%
    6
    100%
    5
    100%
    6
    100%
    0
    0%
    0
    0%
    27
    60%
    Gender of Extension Period Participants (participants) [Number]
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    57.1%
    2
    50%
    10
    22.2%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    6
    42.9%
    2
    50%
    8
    17.8%
    Race: Extension Phase (participants) [Number]
    Black
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    35.7%
    0
    0%
    5
    11.1%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9
    64.3%
    4
    100%
    13
    28.9%
    Eastern Cooperative Oncology Group (ECOG) Performance Status: Initial Treatment Phase (participants) [Number]
    0
    2
    40%
    2
    40%
    1
    16.7%
    0
    0%
    2
    33.3%
    0
    0%
    0
    0%
    7
    15.6%
    1
    3
    60%
    3
    60%
    4
    66.7%
    5
    100%
    3
    50%
    0
    0%
    0
    0%
    18
    40%
    2
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    2
    4.4%
    Eastern Cooperative Oncology Group (ECOG) Performance Status: Extension Phase (participants) [Number]
    0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    14.3%
    1
    25%
    3
    6.7%
    1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    11
    78.6%
    3
    75%
    14
    31.1%
    2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    1
    2.2%
    Body Surface Area (BSA) (m^2) [Mean (Standard Deviation) ]
    Initial Treatment Period
    2.0
    (0.20)
    1.9
    (0.28)
    1.9
    (0.42)
    1.6
    (0.15)
    1.8
    (0.15)
    NA
    (NA)
    NA
    (NA)
    1.9
    (0.27)
    Extension Period
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    1.9
    (0.35)
    1.9
    (0.06)
    1.9
    (0.31)
    Cancer Diagnosis: Initial Treatment Phase (participants) [Number]
    Myelodysplastic syndrome-RA
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    2
    4.4%
    Myelodysplastic syndrome-RARS
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.2%
    Myelodysplastic syndrome-RAEB-T
    1
    20%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    4.4%
    Chronic myelomonocytic leukemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    1
    2.2%
    Solid tumor
    3
    60%
    3
    60%
    5
    83.3%
    5
    100%
    4
    66.7%
    0
    0%
    0
    0%
    20
    44.4%
    Multiple myeloma
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.2%
    Cancer Diagnosis: Extension Phase (participants) [Number]
    Myelodysplastic syndrome-RA
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    1
    2.2%
    Myelodysplastic syndrome-RARS
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    1
    2.2%
    Myelodysplastic syndrome-RAEB-T
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    1
    2.2%
    Chronic myelomonocytic leukemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Solid tumor
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12
    85.7%
    3
    75%
    15
    33.3%
    Multiple myeloma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose
    DescriptionArea under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    455.86
    (26.04)
    897.43
    (31.00)
    921.87
    (39.215)
    1502.86
    (25.57)
    2. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point
    DescriptionArea under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    454.80
    (26.22)
    895.38
    (31.20)
    920.76
    (39.20)
    1505.16
    (25.57)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Geometric means, ratio and 90% confidence interval (CI) of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-t, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value98.4
    Confidence Interval (2-Sided) 90%
    64.0 to 151.3
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 50 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 75 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-t, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value67.5
    Confidence Interval (2-Sided) 90%
    44.7 to 101.8
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 75 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 100 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-t, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value82.7
    Confidence Interval (2-Sided) 90%
    53.8 to 127.2
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 100 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    3. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to Infinity
    DescriptionThe area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine after a single dose, calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation: AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
    460.47
    (25.79)
    897.42
    (30.93)
    945.50
    (39.05)
    1533.37
    (23.96)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-inf, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value97.4
    Confidence Interval (2-Sided) 90%
    63.8 to 148.8
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 50 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 75 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-inf, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value68.5
    Confidence Interval (2-Sided) 90%
    45.7 to 102.7
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 75 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 100 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized AUC0-inf, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value83.2
    Confidence Interval (2-Sided) 90%
    54.5 to 127.1
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 100 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    4. Primary Outcome
    TitleMaximum Plasma Concentration of Azacitidine (Cmax)
    DescriptionThe maximum observed plasma concentration of azacitidine after a single dose on Day 1.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    293.38
    (34.11)
    749.04
    (61.03)
    745.50
    (57.90)
    1261.96
    (39.19)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized Cmax, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value127.7
    Confidence Interval (2-Sided) 90%
    66.3 to 245.7
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 50 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 75 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized Cmax, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value84.7
    Confidence Interval (2-Sided) 90%
    45.3 to 158.5
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 75 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 100 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance models on the nature log-transformed dose-normalized Cmax, obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value107.5
    Confidence Interval (2-Sided) 90%
    55.9 to 207.0
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric means is calculated as Azacitidine 100 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    5. Primary Outcome
    TitleTime to Maximum Plasma Concentration of Azacitidine (Tmax)
    DescriptionThe time to first maximum observed plasma concentration of azacitidine after a single dose on Day 1.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Median (Full Range) [hours]
    0.25
    0.25
    0.25
    0.27
    6. Primary Outcome
    TitleTerminal Phase Half-life of Azacitidine (t½)
    DescriptionThe terminal phase half-life of azacitidine after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [hours]
    1.38
    (27.31)
    0.63
    (35.72)
    1.19
    (102.56)
    1.03
    (78.48)
    7. Primary Outcome
    TitleApparent Total Clearance of Azacitidine (CL/F)
    DescriptionThe apparent total clearance of azacitidine after a single dose on Day 1, calculated as Dose/AUC0-inf.
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [liters/hour]
    104.58
    (25.00)
    105.76
    (17.03)
    151.55
    (30.88)
    106.00
    (25.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance model on the nature log-transformed CL/F obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value101.1
    Confidence Interval (2-Sided) 90%
    71.2 to 143.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 50 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 75 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance model on the nature log-transformed CL/F obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value144.9
    Confidence Interval (2-Sided) 90%
    103.6 to 202.7
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 75 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 100 mg/m^2
    Comments Geometric means, ratio and 90% CI of ratio of geometric means are from one way analysis of variance model on the nature log-transformed CL/F obtained on Day 1. Azacitidine 25 mg/m^2 is the reference group for comparisons.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value101.4
    Confidence Interval (2-Sided) 90%
    71.4 to 143.9
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Azacitidine 100 mg/m^2 / Azacitidine 25 mg/m^2 and expressed as a percentage.
    8. Primary Outcome
    TitleApparent Volume of Distribution of Azacitidine (Vz/F)
    DescriptionThe apparent volume of distribution of azacitidine after a single dose on Day 1, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz)
    Time FrameDay 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants with normal renal function only.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.
    Measure Participants5565
    Geometric Mean (Geometric Coefficient of Variation) [liters]
    208.69
    (45.57)
    96.74
    (36.75)
    259.44
    (121.71)
    456.69
    (99.41)
    9. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine
    DescriptionThe effect of renal impairment on azacitidine pharmacokinetics was analyzed by comparing PK parameters obtained on Days 1 and 5 from participants with severe renal impairment and those with normal renal function. Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    921.87
    (39.15)
    1558.32
    (64.95)
    Day 5
    843.03
    (12.00)
    1183.61
    (51.92)
    10. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine
    DescriptionThe area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule for participants with normal renal function and for participants with severe renal impairment.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    920.76
    (39.20)
    1558.72
    (65.02)
    Day 5
    841.62
    (11.83)
    1181.83
    (51.98)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of AUC0-t after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value169.3
    Confidence Interval (2-Sided) 90%
    109.2 to 262.5
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of AUC0-t after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value140.4
    Confidence Interval (2-Sided) 90%
    90.6 to 217.7
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    11. Primary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine
    DescriptionThe area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine, after a single dose (Day 1) and multiple doses (Day 5), calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation: AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    946.22
    (39.05)
    1573.82
    (63.46)
    Day 5
    857.64
    (9.94)
    1210.92
    (49.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of AUC0-inf after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value166.3
    Confidence Interval (2-Sided) 90%
    108.6 to 254.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of AUC0-inf after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value141.2
    Confidence Interval (2-Sided) 90%
    92.2 to 216.2
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    12. Primary Outcome
    TitleMaximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine
    DescriptionThe maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and for participants with severe renal impairment.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    745.50
    (57.90)
    1056.66
    (93.01)
    Day 5
    632.56
    (45.86)
    668.11
    (91.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of Cmax after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value141.7
    Confidence Interval (2-Sided) 90%
    73.2 to 274.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of Cmax after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRatio (%) of Geometric Means
    Estimated Value105.6
    Confidence Interval (2-Sided) 90%
    54.5 to 204.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsRatio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
    13. Primary Outcome
    TitleTime to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine
    DescriptionThe time to first maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    0.25
    0.50
    Day 5
    0.38
    0.64
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of Tmax after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.1342
    Comments
    MethodWilcoxon (Mann-Whitney)
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value0.25
    Confidence Interval (2-Sided) 90%
    0 to 0.52
    Parameter Dispersion Type:
    Value:
    Estimation CommentsMedian difference is Severe RI - Normal RF.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Azacitidine 25 mg/m^2, Azacitidine 50 mg/m^2
    Comments Comparison of Tmax after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesisp-Value0.1017
    Comments
    MethodWilcoxon (Mann-Whitney)
    Comments
    Method of EstimationEstimation ParameterMedian Difference (Final Values)
    Estimated Value0.25
    Confidence Interval (2-Sided) 90%
    0 to 0.50
    Parameter Dispersion Type:
    Value:
    Estimation CommentsMedian difference is Severe RI - Normal RF.
    14. Primary Outcome
    TitleTerminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine
    DescriptionThe terminal phase half-life of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    1.19
    (102.56)
    0.97
    (43.88)
    Day 5
    1.03
    (76.95)
    1.15
    (53.86)
    15. Primary Outcome
    TitleApparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine
    DescriptionThe apparent total clearance of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated as Dose/AUC0-inf.
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    151.55
    (30.88)
    85.76
    (68.83)
    Day 5
    166.95
    (27.59)
    111.55
    (51.75)
    16. Primary Outcome
    TitleApparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine
    DescriptionThe apparent volume of distribution of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz).
    Time FrameDay 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.
    Arm/Group TitleNormal RF: Azacitidine 75 mg/m^2Severe RI: Azacitidine 75 mg/m^2
    Arm/Group DescriptionParticipants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.
    Measure Participants66
    Day 1
    259.44
    (121.71)
    120.47
    (120.45)
    Day 5
    248.57
    (115.10)
    184.54
    (104.34)
    17. Primary Outcome
    TitleNumber of Participants With Adverse Events (AEs)
    DescriptionA serious adverse event is one that at any dose of the study drug or at any time during the period of observation: Results in death; Is life threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is medically important. The Investigator assessed each AE for potential causal relationship between the event and study drug. The intensity of adverse changes in physical signs or symptoms was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
    Time FrameInitial treatment phase: Days 1-11 for participants who received a single dose; Days 1-29 for participants who received multiple doses. Extension treatment period: From the date of first dose until 28 days after the date of last dose (up to 7 months).

    Outcome Measure Data

    Analysis Population Description
    Safety population, all enrolled patients who received at least one dose of azacitidine and who had at least one post-treatment safety assessment.
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function (RF) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.Participants with severe renal impairment (RI) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.
    Measure Participants55656144
    Any adverse event
    4
    80%
    3
    60%
    6
    100%
    5
    100%
    6
    100%
    14
    100%
    4
    100%
    Adverse event related to study drug
    2
    40%
    3
    60%
    4
    66.7%
    4
    80%
    3
    50%
    8
    57.1%
    2
    50%
    Serious adverse event
    0
    0%
    0
    0%
    4
    66.7%
    1
    20%
    1
    16.7%
    8
    57.1%
    3
    75%
    Serious adverse event related to study drug
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    1
    7.1%
    1
    25%
    Grade 3 or 4 adverse event
    0
    0%
    0
    0%
    4
    66.7%
    1
    20%
    3
    50%
    10
    71.4%
    3
    75%
    AE leading to study drug discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    28.6%
    2
    50%
    AE leading to study drug interruption
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    28.6%
    1
    25%
    AE leading to a dose reduction
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    AE leading to other action taken
    2
    40%
    1
    20%
    6
    100%
    4
    80%
    5
    83.3%
    10
    71.4%
    3
    75%
    Death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    1
    25%

    Adverse Events

    Time FrameInitial treatment phase: Days 1-11 for participants who received a single dose; Days 1-29 for participants who received multiple doses. Extension treatment period: From the date of first dose until 28 days after the date of last dose (up to 7 months).
    Adverse Event Reporting Description
    Arm/Group TitleAzacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Arm/Group DescriptionParticipants with normal renal function (defined as creatinine clearance > 80 mL/min/1.73m^2) received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1.Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1.Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1.Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5.Participants with normal renal function (RF) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.Participants with severe renal impairment (RI) received up to 6 cycles of treatment with 75 mg/m^2 azacitidine daily on Days 1-7 of each 28-day cycle.
    All Cause Mortality
    Azacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Azacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/5 (0%) 0/5 (0%) 4/6 (66.7%) 1/5 (20%) 1/6 (16.7%) 8/14 (57.1%) 3/4 (75%)
    Blood and lymphatic system disorders
    Anemia0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Pancytopenia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Gastrointestinal disorders
    Nausea0/5 (0%) 0/5 (0%) 2/6 (33.3%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Small intestinal obstruction0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 1/4 (25%)
    Vomiting0/5 (0%) 0/5 (0%) 2/6 (33.3%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    General disorders
    Device dislocation0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Fatigue0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Non-cardiac chest pain0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Pyrexia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Infections and infestations
    Urinary tract infection0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injury, poisoning and procedural complications
    Post procedural fistula0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Investigations
    Hemoglobin decreased0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Metabolism and nutrition disorders
    Dehydration0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Hyponatremia0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Nervous system disorders
    Dizziness0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Psychiatric disorders
    Confusional state0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Renal and urinary disorders
    Renal failure0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Renal vein thrombosis0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Renal failure acute0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 1/4 (25%)
    Dyspnea0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 2/4 (50%)
    Other (Not Including Serious) Adverse Events
    Azacitidine 25 mg/m^2Azacitidine 50 mg/m^2Azacitidine 75 mg/m^2Azacitidine 100 mg/m^2Severe RI: Azacitidine 75 mg/m^2Extension Phase: Normal RFExtension Phase: Severe RI
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/5 (80%) 3/5 (60%) 5/6 (83.3%) 5/5 (100%) 6/6 (100%) 9/14 (64.3%) 4/4 (100%)
    Blood and lymphatic system disorders
    Anaemia0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 2/6 (33.3%) 1/14 (7.1%) 1/4 (25%)
    Leukopenia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 2/14 (14.3%) 1/4 (25%)
    Lymphadenopathy0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Neutropenia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 2/6 (33.3%) 2/14 (14.3%) 2/4 (50%)
    Pancytopenia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Thrombocytopenia0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 2/14 (14.3%) 0/4 (0%)
    Cardiac disorders
    Bradycardia0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Cardiac failure congestive0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Palpitations0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Gastrointestinal disorders
    Constipation1/5 (20%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 4/14 (28.6%) 1/4 (25%)
    Diarrhoea0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 1/4 (25%)
    Dyspepsia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Dysphagia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 2/14 (14.3%) 0/4 (0%)
    Eructation0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Gastric ulcer0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Gastrooesophageal reflux disease0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 2/14 (14.3%) 0/4 (0%)
    Nausea0/5 (0%) 0/5 (0%) 1/6 (16.7%) 2/5 (40%) 0/6 (0%) 2/14 (14.3%) 2/4 (50%)
    Vomiting0/5 (0%) 0/5 (0%) 3/6 (50%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    General disorders
    Asthenia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 1/4 (25%)
    Catheter site erythema0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Catheter site pain0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Chills0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 1/4 (25%)
    Fatigue0/5 (0%) 0/5 (0%) 2/6 (33.3%) 3/5 (60%) 2/6 (33.3%) 3/14 (21.4%) 1/4 (25%)
    Gait disturbance1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Hernia pain0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Influenza like illness0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Injection site discomfort0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Injection site erythema1/5 (20%) 1/5 (20%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 1/14 (7.1%) 0/4 (0%)
    Injection site haematoma0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injection site haemorrhage0/5 (0%) 1/5 (20%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injection site induration1/5 (20%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Injection site pain0/5 (0%) 2/5 (40%) 1/6 (16.7%) 1/5 (20%) 2/6 (33.3%) 0/14 (0%) 0/4 (0%)
    Injection site pruritus1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Injection site rash0/5 (0%) 1/5 (20%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injection site reaction0/5 (0%) 0/5 (0%) 2/6 (33.3%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injection site swelling0/5 (0%) 0/5 (0%) 1/6 (16.7%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Injection site vesicles0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Non-cardiac chest pain0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Pyrexia0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Infections and infestations
    Bronchitis0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Oral candidiasis0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Otitis media0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Postoperative wound infection0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Urinary tract infection0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 1/4 (25%)
    Injury, poisoning and procedural complications
    Procedural site reaction0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Investigations
    Cardiac murmur0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Neutrophil count decreased0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Platelet count increased0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Weight decreased0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Metabolism and nutrition disorders
    Decreased appetite0/5 (0%) 0/5 (0%) 2/6 (33.3%) 1/5 (20%) 0/6 (0%) 2/14 (14.3%) 0/4 (0%)
    Dehydration0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Hyperkalaemia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 1/4 (25%)
    Hypomagnesaemia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Hyponatraemia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Malnutrition0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 2/14 (14.3%) 0/4 (0%)
    Back pain0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Bone pain1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Flank pain0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Muscular weakness0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Musculoskeletal pain1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Vaginal neoplasm0/5 (0%) 1/5 (20%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Nervous system disorders
    Headache0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 2/14 (14.3%) 0/4 (0%)
    Hypoaesthesia0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Neuropathy peripheral1/5 (20%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Psychiatric disorders
    Depression0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Psychiatric symptom0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Renal and urinary disorders
    Haematuria0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Reproductive system and breast disorders
    Vaginal haemorrhage0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Vulval disorder0/5 (0%) 0/5 (0%) 1/6 (16.7%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 1/14 (7.1%) 0/4 (0%)
    Dyspnoea0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 2/14 (14.3%) 1/4 (25%)
    Hiccups0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)
    Pulmonary oedema0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 1/4 (25%)
    Rales0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Rhinorrhoea1/5 (20%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Skin and subcutaneous tissue disorders
    Erythema0/5 (0%) 1/5 (20%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Pruritus generalised0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 1/6 (16.7%) 0/14 (0%) 0/4 (0%)
    Vascular disorders
    Hot flush0/5 (0%) 0/5 (0%) 0/6 (0%) 1/5 (20%) 0/6 (0%) 0/14 (0%) 0/4 (0%)
    Peripheral coldness0/5 (0%) 0/5 (0%) 0/6 (0%) 0/5 (0%) 0/6 (0%) 1/14 (7.1%) 0/4 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (30) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.

    Results Point of Contact

    Name/TitleAssociate Director, Clinical Trials Disclosure
    OrganizationCelgene Corporation
    Phone1-888-260-1599
    Emailclinicaltrialdisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT00652626
    Other Study ID Numbers:
    • AZA PH US 2007 PK006
    First Posted:
    Apr 4, 2008
    Last Update Posted:
    Nov 19, 2019
    Last Verified:
    Nov 1, 2019