A Study to Evaluate CC-486/Onureg in Participants With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Participants With Myeloid Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of moderate or severe liver impairment on the drug levels of oral azacitidine and the safety and tolerability of oral azacitidine in participants with myeloid malignancies.

Official Title
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A Phase 1, Multicenter, Open-label Study to Evaluate the Pharmacokinetics of CC-486 (Onureg®) in Subjects With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Adult Subjects With Myeloid Malignancies

Conditions
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Hepatic Insufficiency, Neoplasms

Intervention / Treatment
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* Drug: Onureg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of Myelodysplastic syndrome, Acute myeloid leukemia, Non-acute promyelocytic leukemia, Chronic myelomonocytic leukemia, Philadelphia-negative myeloproliferative neoplasms, Myelodysplastic syndrome Myeloproliferative neoplasms overlap, Accelerated phase and blast phase Myeloproliferative neoplasms, Blastic plasmacytoid dendritic cell neoplasm according to the World Health Organization (WHO) 2016 classification Life expectancy of ≥ 3 months Stable renal function without dialysis for at least 2 months prior to investigational product administration Has moderate or severe hepatic impairment as defined by National Cancer Institute Organ Dysfunction Working Group criteria Exclusion Criteria: Chemotherapy or radiotherapy within 2 weeks or 5 half-lives, whichever is longer, prior to the first day of investigational product administration Persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2 Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study History of inflammatory bowel disease, celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption of the investigational product and/or predispose the participant to an increased risk of gastrointestinal toxicity Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Drug: Onureg<br>* Specified dose on specified days<br>* Other names: CC-486, Oral Azacitidine;|
| Experimental: Group 2<br> | Drug: Onureg<br>* Specified dose on specified days<br>* Other names: CC-486, Oral Azacitidine;|
| Other: Group 3<br>Control - participants with normal hepatic function | Drug: Onureg<br>* Specified dose on specified days<br>* Other names: CC-486, Oral Azacitidine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t: Estimation of area under the plasma concentration-time curve (AUC) calculated from time zero to the last measured time point |  | Day 1 | 
| AUC0-∞: Estimation of AUC calculated from time zero to infinity |  | Day 1 | 
| Cmax: Observed maximum concentration |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 9 Months | 
| Incidence of serious adverse events |  | Up to 9 Months | 
| Number of participants with clinically significant changes in electrocardiogram parameters |  | Up to 9 Months | 
| Incidence of clinically significant changes in vital signs: Body temperature |  | Up to 9 Months | 
| Incidence of clinically significant changes in vital signs: Respiratory rate |  | Up to 9 Months | 
| Incidence of clinically significant changes in vital signs: Blood pressure |  | Up to 9 Months | 
| Incidence of clinically significant changes in vital signs: Heart rate |  | Up to 9 Months | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 9 Months | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |  | Up to 9 Months | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | Up to 9 Months | 
| Number of Participants with clinically significant changes in Eastern Cooperative Oncology Group (ECOG) performance status |  | Up to 9 Months | 
| Incidence of clinically significant changes in clinical laboratory results: Liver Function tests |  | Up to 9 Months | 
| Number of clinically significant changes in physical examinations |  | Up to 9 Months | 
| Number of participants with a recording of concomitant medications |  | Up to 9 Months | 
| Number of participants with a recording of concomitant procedures |  | Up to 9 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-486, Azacitidine, Hepatic Impairment, Onureg, Myeloid Malignancies