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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
To assess the bioequivalence of Vidaza® and Luitpold Azacitidine pharmacokinetics, in terms of Cmax, AUC0-t and AUC0-∞, following SC administration. To assess the comparative safety of Vidaza® versus Luitpold Azacitidine during the 2 day study period.

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

Conditions
-----------------
Myelodysplastic Syndrome, Myelofibrosis, Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Drug: Luitpold Azacitidine
* Drug: Vidaza®


Participation Criteria
=================
Eligibility Criteria
-----------------
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. 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 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 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Luitpold Azacitidine<br> | Drug: Luitpold Azacitidine<br>* Subcutaneous (SC) at a dose of 75 mg/m2 per day on days 1 and 2 of a treatment cycle<br>|
| Active Comparator: Vidaza®<br> | Drug: Vidaza®<br>* Subcutaneous (SC) at a dose of 75 mg/m2 per day on days 1 and 2 of a treatment cycle<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Concentration Time Curve (AUC0-t) | Pharmacokinetic Analysis | Blood will be drawn pre-dose, and 0.125, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours after dosing on days 1 and 2 | 
| Area under the Concentration Time Curve Extrapolated to Infinity (AUC0-∞) | Pharmacokinetic Analysis | Blood will be drawn pre-dose, and 0.125, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours after dosing on days 1 and 2 | 
| Observed maximal concentration (Cmax) |  | Blood will be drawn pre-dose, and 0.125, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours after dosing on days 1 and 2 |