Study to Evaluate Pharmacokinetics, Food Effect, Safety and Efficacy of Oral Azacitidine

Celgene

Status and phase

Completed

Phase 1

Conditions

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Chronic

Myelodysplastic Syndromes

Treatments

Drug: oral azacitidine

Study type

Interventional

Funder types

Industry

Identifiers

NCT01519011

T-AZA-006 (Other Identifier)

AZA-MDS-004

Details and patient eligibility

About

The primary purpose of this study is to evaluate the pharmacokinetics of oral azacitidine when administered once daily as two 150-mg tablets, including the effect of food, and to evaluate the bioavailability of oral azacitidine 300-mg when administered as two 150-mg tablets relative to three 100-mg tablets.

Enrollment

34 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18 years or older at the time of signing the informed consent document
Diagnosis of Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
At least 3 month life expectancy
Adequate organ function, defined as:
- Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the ULN;
- Serum creatinine ≤ 1.5 times the ULN;
- Serum bicarbonate ≥ 20 mEq/L
Females of childbearing potential (FCBP) must:
- Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following the last dose of oral azacitidine; and
- Have a negative serum or urine pregnancy test (investigator's discretion; sensitivity of at least 25 mIU/mL) at screening; and
- Have a negative serum or urine pregnancy test (investigator's discretion; sensitivity of at least 25 mIU/mL) within 72 hours prior to Day 1 of the pharmacokinetic (PK) phase (note that the screening pregnancy test can be used as the test prior to Day 1 of the PK phase if it is performed within the 72 hour timeframe).
Males with partners who are FCBP must agree that they and their partners will use at least two effective contraceptive methods throughout the study and will avoid fathering a child for 3 months following the date of last oral azacitidine dosing
Understand and voluntarily sign an informed consent document prior to the start of any study related assessments/procedures
Able to adhere to the study visit schedule and other protocol requirements

Exclusion criteria

Suspected or proven acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
Previous treatment with azacitidine or other demethylating agents within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
Anticancer therapy (standard or investigational) within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
Use of any proton pump inhibitor or any other agent that may affect gastric acid level within 28 days prior to study therapy (only applicable to Part II of the PK phase)
Concurrent use of erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, except that the subject is on a stable dose for at least 4 weeks (28 days) prior to starting study therapy
Concurrent use of iron-chelating agents, except that the subject is on a stable dose for at least 8 weeks (56 days) prior to starting study therapy
Concurrent corticosteroid use, except for medical conditions other than Myelodysplastic Syndrome and provided the subject is on a stable or decreasing dose for ≥ 1 week prior to start study therapy
Pregnant or lactating females
Any known or suspected hypersensitivity to azacitidine or mannitol or any other ingredient used in the manufacture of oral azacitidine (see the azacitidine IB)
Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C
Presence of gastrointestinal disease, malignant hepatic tumors, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
Current congestive heart failure (New York Heart Association Class III-IV Appendix G), unstable angina or angina requiring surgical or medical intervention within 6 months prior to starting study therapy, myocardial infarct within 6 months prior to starting study therapy, or uncontrolled cardiac arrhythmia (defined as arrhythmia that is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia). Subjects with controlled atrial fibrillation that is asymptomatic are eligible
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Any condition that confounds the ability to interpret data from the study

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

None (Open label)

34 participants in 7 patient groups

1: A, B, C

Experimental group

Description: