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

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

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

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Oral azacitidine

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Celgene Trial Site
  • Hiroshima, Japan
    • Celgene Trial Site
  • Nagoya, Japan
    • Celgene Trial Site
  • Osaka, Japan
    • Celgene Trial Site
  • Tokyo, Japan
    • Celgene Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Masamitsu Harata, Celgene K.K.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 5, 2012

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: AZA-MDS-005