Blinded Cross-Over Bioequivalence (BE) Trial of Luitpold Azacitidine vs Vidaza

Blinded Cross-over Bioequivalence Trial of Luitpold Azacitidine Versus Vidaza® in Patients With Myelodysplastic Syndrome, Myelofibrosis, Chronic Myeloid Leukemia or Chronic Lymphocytic Leukemia

The purpose of this study is to assess the bioequivalence of subcutaneous Vidaza® and subcutaneous Luitpold Azacitidine pharmacokinetics and to assess the comparative safety of subcutaneous Vidaza® versus subcutaneous Luitpold Azacitidine.

To assess the bioequivalence of Vidaza® and Luitpold Azacitidine pharmacokinetics, in terms of Maximal Concentration (Cmax), Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t), and Area Under the Curve From Time Zero Extrapolated to Infinity (AUC 0-∞), following SC administration.

To assess the comparative safety of Vidaza® versus Luitpold Azacitidine during the 2 day study period.

Inclusion Criteria:

• Signed informed consent obtained prior to initiation of any study-specific procedures.
• Patients with one of the following - myelodysplastic syndrome of the following French-American- British (FAB) subtypes: refractory anemia (RA), RA with ringed sideroblasts (if accompanied by neutropenia, or thrombocytopenia, or requiring transfusion), RA with excess of blasts (RAEB), RAEB in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMMoL); myelofibrosis; chronic myeloid leukemia; or chronic lymphocytic leukemia who's physician feels should receive azacitidine.
• Male or female patients aged at least 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Life expectancy > or = to 3 months.
• Adequate organ function, including the following: Hepatic - Total bilirubin < or = to 1.5 x the upper limit of normal (ULN), aspartate transaminases (AST) and alanine transaminases (ALT) < or = to 2 x ULN and Renal - Serum creatinine < or = to 1.5 x ULN.
• Female patients of child-bearing potential must have a negative pregnancy test and must be using at least one form of contraception as approved by the Investigator for 4 weeks prior to the study and 4 months after the last dose of azacitidine.
• Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of azacitidine.

Exclusion Criteria:

• Hypersensitivity to azacitidine or mannitol.
• Anticipated need for red blood cells (RBC) or platelet transfusion 2 days prior to or up to 2 days after treatment initiation.
• Chemotherapy (excluding previous azacitidine treatment) or radiotherapy within 4 weeks of randomization (6 weeks for nitrosoureas or mitomycin C).
• Significant electrophysical abnormalities in pre-trial EKG.
• Present history of locally advanced or metastatic malignant disease or leukemia.
• Use of recreational drugs or history of drug addiction, within the prior 6 months.
• Known history of a positive hepatitis screen, including hepatitis B surface antigens or hepatitis C virus (HCV) antibodies.
• Known history of HIV or syphilis.
• History of clinically significant adverse events due to chemotherapy, radiotherapy or investigational agents.
• Presence of an advanced malignant hepatic tumor.
• Presence of an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders.
• Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patients compliance.
• Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry.
• Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception.