A PHASE 1, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS AND EFFECT OF FOOD OF A NEW TABLET FORMULATION OF ORAL AZACITIDINE, AND TO EVALUATE THE SAFETY AND EFFICACY OF ORAL AZACITIDINE IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES, CHRONIC MYELOMONOCYTIC LEUKEMIA OR ACUTE MYELOID LEUKEMIA
Overview
- Phase
- Phase 1
- Intervention
- oral azacitidine
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- Celgene
- Enrollment
- 34
- Locations
- 8
- Primary Endpoint
- PK-(T½)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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:
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)
Arms & Interventions
1: A, B, C
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
2: B, C, A
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
3: C, A, B
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
4: B, A, C
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
5: A, C, B
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
6: C, B, A
Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition.
Intervention: oral azacitidine
Extension
300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle.
Intervention: oral azacitidine
Outcomes
Primary Outcomes
PK-(T½)
Time Frame: Up to 10 days
PK-Terminal half-life (T½)
PK-(Cmax)
Time Frame: Up to 10 days
Observed maximum concentration in plasma (Cmax)
PK-(Tmax)
Time Frame: Up to 10 days
PK-Time to maximum plasma concentration (Tmax)
PK-(AUC)
Time Frame: Up to 10 days
PK-Area under the plasma concentration time curve (AUC)
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine
Time Frame: Up to 10 days
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine.
Secondary Outcomes
- Adverse Events(Up to 2 years)
- Hematological response/improvement(Up to 2 years)
- Transfusion independence(Up to 2 years)
- Platelet transfusion independence(Up to 2 years)