A Phase 1 Study to Evaluate the Pharmacokinetics and Tolerability of Oral Azacitidine in Japanese Patients With Myelodysplastic Syndromes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the tolerability of oral azacitidine in the treatment of patients with Myelodysplastic Syndromes (MDS).

Official Title
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A Phase 1, Multicenter, Open-label Study to Evaluate the Pharmacokinetics and Tolerability of Oral Azacitidine in Japanese Subjects With Myelodysplastic Syndromes

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Oral azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must satisfy the following criteria to be enrolled in the study: Have a documented diagnosis of myelodysplastic syndromes (MDS) according to World Health Organization (WHO) 2008 classification Age ≥ 20 years; Written informed consent; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Resolution of any toxic effects of prior anti-cancer therapy; and Negative urine or serum pregnancy test on females of childbearing potential. Exclusion Criteria: The presence of any of the following will exclude a patient from enrollment: Treatment with chemotherapy, radiotherapy, or surgery within 4 weeks of study registration; Pregnant or breast-feeding females; Previous or concomitant malignancy other than MDS; Significant active cardiac disease within the previous 6 months; Uncontrolled systemic infection or Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

Ages Eligible for Study
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Minimum Age: 20 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral azacitidine<br> | Drug: Oral azacitidine<br>* Patients will receive 300 mg dose of oral azacitidine administered once daily for the first 21 days of each 28-day treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events | Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK- Maximum concentration in plasma (Cmax) | PK- Maximum concentration in plasma (Cmax) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK- Time to maximum plasma concentration (Tmax) | PK- Time to maximum plasma concentration (Tmax) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK-Elimination rate constant (Kel) | PK-Elimination rate constant (Kel) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK-Terminal half-life (T1/2,z) | PK-Terminal half-life (T1/2,z) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK-Area under the plasma concentration-time curve (AUC) | PK-Area under the plasma concentration-time curve (AUC) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK-Apparent total body clearance (CL/F) | PK-Apparent total body clearance (CL/F) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| PK-Apparent volume of distribution (Vz/f) | PK-Apparent volume of distribution (Vz/f) | 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 hours post-dose | 
| Safety (type, frequency, severity, number of participants with adverse events) | Safety (type, frequency, severity, number of participants with adverse events) | Up to 2 years | 
| Efficacy (Hematologic response and hematologic improvement) | Efficacy (Hematologic response and hematologic improvement) | Up to 2 years |