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.

Study Overview

• Status: Completed
• Conditions: Myelofibrosis; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Luitpold Azacitidine; Drug: Vidaza®

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19403
      • Luitpold Pharmaceuticals, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Luitpold Azacitidine first, then Vidaza®; Participants first received Luitpold Azacitidine subcutaneously (SC) on Day 1. After a washout period of 24 hours, they then received Vidaza on Day 2.	Drug: Luitpold Azacitidine; Subcutaneous (SC) at a dose of 75 mg/m^2 per day on days 1 and 2 of a treatment cycle; Other Names: Single use vials containing 100 mg azacitidine/vials,.The formulation contained mannitol as an excipient. Lot 090035 and Lot 120011
Active Comparator: Vidaza® first, then Luitpold Azacitidine; Participants first received Vidaza subcutaneously (SC) on Day 1. After a washout period of 24 hours, they then received Luitpold Azacitidine on Day 2.	Drug: Vidaza®; Subcutaneous (SC) at a dose of 75 mg/m^2 per day on days 1 and 2 of a treatment cycle; Other Names: Vidaza (azacitidine for injection), Celegene Corporation, commercially available formulation. The formulation contained mannitol as a excipient. Lot 91096A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t)	The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC 0-t is defined as AUC from time 0 to the last data point	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 Curve From Time Zero Extrapolated to Infinity (AUC 0-∞)	The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC 0-∞ is defined as area under the concentration vs. time curve from zero to infinity.	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)	Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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

Collaborators and Investigators

• Sponsor: American Regent, Inc.
• Investigators: Study Director: Joseph Perno, MD,PhD, Medical director

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 21, 2012

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (Estimated): February 7, 2011

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Precancerous Conditions; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Preleukemia; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Primary Myelofibrosis; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Diuretics; Natriuretic Agents; Diuretics, Osmotic; Azacitidine; Mannitol
• Other Study ID Numbers: 1AZA10001