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A Multi-Center Relative Bioavailability Study of Azacitidine 75 mg/m2 Subcutaneous Injection In Myelodysplastic Syndrome Patients Under Fasting Conditions

Phase 1
18 Years
Open (Enrolling)
Myelodysplastic Syndrome

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Trial Information

A Multi-Center Relative Bioavailability Study of Azacitidine 75 mg/m2 Subcutaneous Injection In Myelodysplastic Syndrome Patients Under Fasting Conditions

This study is an open label, multi-center randomized, single dose, two-treatment,
two-period, two-sequence, two-way cross-over, relative bioavailability study of Azacitidine
for Injection for suspension use manufactured for Bioniche Pharma USA LLC compared with
Vidaza® manufactured by Celgene Corporation in MDS patients under fasting conditions.
Patients who are on a stable 75 mg/m2 dose of Vidaza will be randomized to study drug
sequence Azacitidine on C1D1/ Vidaza® on C2D1 or Vidaza® on C1D1 / Azacitidine on C2D1.
Randomization will be in a 2:2 ratio. Thirty-six (36) patients will be enrolled to ensure
28 evaluable patients. Patients will not be blinded to their treatment assignment.

After randomization, fasted patients will receive 1 dose of assigned study drug (either
Azacitidine for Injection or Vidaza®) subcutaneously at a dose of 75 mg/m2 on C1D1. On
Days 2-7, they will receive their normal Vidaza® treatment. Following a 21 day rest period,
patients will cross over to receive the alternate treatment on C2D1 followed by their normal
Vidaza®) treatment on Cycle 2 Days 2-7. The Final Patient Visit will be conducted 7 days
following the last dose of Vidaza®.

The total duration of the study for each patient will be up to 56 days including the
Screening period and Post Study Visit.

Inclusion Criteria:

- Male or female patients with age >18 years.

- Patients with Myelodysplastic Syndrome (MDS) placed on Vidaza® according to the
Marketing Authorization issued in the country in which the clinical study is being
conducted (i.e., in the US, patients with any of the following
French-American-British ( FAB) subtypes: Refractory Anemia (RA), Refractory Anemia
with Ringed Sideroblasts (RARS), (if accompanied by neutropenia or thrombocytopenia
or requiring transfusions), Refractory Anemia with Excess Blasts (RAEB), Refractory
Anemia with Excess Blasts in Transformation (RAEB-T) and Chronic Myelomonocytic
Leukemia (CMMoL); in France, subjects who are not eligible for hematopoietic stem
cell transplantation: with intermediate -2 and high-risk myelodysplastic syndromes
according to the International Prognostic Scoring System (IPSS) or chronic
myelomonocytic leukemia (CMML) with 10-29% marrow blasts without myeloproliferative
disorder) and who currently receive Vidaza at 75 mg/m2;

- Patient life expectancy > 6 months.

- Patients with performance status of 0 - 2 as per ECOG Scale.

- Patients with Total Bilirubin < 1.5 x ULN; ALT/AST < 2 x ULN, Serum Creatinine < 1.5
ULN, Serum Bicarbonate > 19 mEq/L.

- Patients who have signed the Informed Consent Form.

Exclusion Criteria:

- Patients with a history of alcoholism or drug addiction (during past 2 years)

- Patients with severe hepatic impairment, impaired renal function, and any condition
which in the Investigator's opinion would be contraindicated or would interfere with
absorption of the study drug.

- Patients whose clinical laboratory test values are outside the reference range may be
re-tested at the discretion of the Investigator. If the clinical values are outside
the range on re-testing, the patient will not be eligible to participate in the study
unless the Investigator deems the result not to be significant.

- Patients with any other active malignancy within the past 5 years except for
cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma
of the skin.

- Patients who have a history of allergic responses to the class of drug being tested.

- Patients with hypersensitivity to Mannitol.

- Patients should not have donated blood and/or plasma for at least thirty (30) days
prior to the first dosing of the study drug. Patients should not have had any
transfusion of blood products for at least 7 days prior.

- Patients who have taken any investigational drug within thirty (30) days prior to the
first dosing of the study.

- Female patients who are pregnant, breast-feeding, or who are likely to become
pregnant during the study. Female patients of child bearing potential will be
instructed to either abstain from sexual intercourse or use an acceptable method of
birth control during the course of the study and for 3 months afterward. Male
patients or their female partners should also use an acceptable method of birth

- Any patient whom the Investigator believes will not be a good candidate for the

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Outcome Measure:

Measurement of Azacitidine in Plasma Samples for Determination of Cmax, AUC0-t, and AUC0-Inf

Outcome Description:

Pharmacokinetic samples will be collected pre-dose and at 12 timepoints post-dose for determination of the level of azacitidine. The relative bioavailability of test to reference drug will be evaluated. If the Cmax, AUC0-t and AUC0-inf 90% confidence intervals for the geometric mean ratio all lie within 80-125% for Azacitidine then bioequivalence is concluded.

Outcome Time Frame:

13 timepoints from pre-dose to 8 hours post dose

Safety Issue:


Principal Investigator

Pierre FENAUX, MD Professor

Investigator Role:

Study Chair

Investigator Affiliation:

Service d'hématologie clinique- Hôpital Avicenne


United States: Food and Drug Administration

Study ID:




Start Date:

April 2011

Completion Date:

November 2012

Related Keywords:

  • Myelodysplastic Syndrome
  • Bioequivalence
  • Myelodysplastic Syndrome
  • MDS
  • Azacitidine
  • Myelodysplastic Syndromes
  • Preleukemia



Holy Cross Hospital Fort Lauderdale, Florida  33308
Wilshire Oncology Medical Group Glendora, California  91741
Pacific Cancer Medical Center Inc. Anaheim, California  92801
California Cancer Associates Fresno, California  93720