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Bioequivalence Study of Azacitidine for Injection in Myelodysplastic Syndrome (MDS) Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2012 by Bioniche Pharma USA LLC.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Bioniche Pharma USA LLC
ClinicalTrials.gov Identifier:
NCT01152346
First received: June 25, 2010
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

The purpose of the study is to determine the bioavailability of Azacitidine for Injection relative to Vidaza® in MDS patients under fasting conditions. The data will be evaluated statistically to determine if the products meet bioequivalence criteria.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Azacitidine for Injection
Drug: Vidaza®
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Multi-Center Relative Bioavailability Study of Azacitidine 75 mg/m2 Subcutaneous Injection In Myelodysplastic Syndrome Patients Under Fasting Conditions

Resource links provided by NLM:


Further study details as provided by Bioniche Pharma USA LLC:

Primary Outcome Measures:
  • Measurement of Azacitidine in Plasma Samples for Determination of Cmax, AUC0-t, and AUC0-Inf [ Time Frame: 13 timepoints from pre-dose to 8 hours post dose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
    Safety will be assessed through monitoring of adverse events and laboratory measures.


Estimated Enrollment: 36
Study Start Date: April 2011
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
ARM 1
Sequence- Azacitidine followed by Vidaza®
Drug: Azacitidine for Injection
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment
Drug: Vidaza®
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment
ARM 2
Sequence-Vidaza® followed by Azacitidine
Drug: Azacitidine for Injection
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment
Drug: Vidaza®
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 control.
  • Any patient whom the Investigator believes will not be a good candidate for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01152346

Locations
United States, California
Pacific Cancer Medical Center Inc. Recruiting
Anaheim, California, United States, 92801
Contact: Veena Charu, MD    714-999-1465    veenacharu@gmail.com   
Principal Investigator: Veena Charu, MD         
Wilshire Oncology Medical Group Recruiting
Corona, California, United States, 92879
Contact: Misagh Karimi, MD    951-898-2828    Misagh.karimi@usoncology.com   
Principal Investigator: Misagh Karimi, MD         
California Cancer Associates Recruiting
Fresno, California, United States, 93720
Contact: Steven Hager, MD    559-326-1222    shager@ccare.com   
Principal Investigator: Steven Hager, MD         
United States, Florida
Holy Cross Hospital Recruiting
Fort Lauderdale, Florida, United States, 33308
Contact: Manjesh Lingamurthy, MD    954-267-7700    Manjesh.Lingamurthy@holy-cross.com   
Principal Investigator: Manjesh Lingamurthy, MD         
France
Service d'hématologie clinique Hôpital Avicenne Recruiting
Bobigny cedex, France, 93009
Contact: Pierre FENAUX, MD,Professor    33 1 48 95 70 71    pierre.fenaux@avc.aphp.fr   
Principal Investigator: Pierre FENAUX, MD,Professor         
CHU de Brest- Hôpital Morvan Recruiting
Brest, France, 29609
Contact: Jean-Richard EVEILLARD, MD    33 2 98 22 35 64    jean-richard.eveillard@chu-brest.fr   
Principal Investigator: Jean-Richard EVEILLARD, MD         
Centre Hospitalier Lyon Sud Recruiting
Lyon, France, 69495
Contact: Mauricette MICHALLET, MD Professor    33 4 72 11 74 32    mauricette.michallet@chu-lyon.fr   
Principal Investigator: Mauricette MICHALLET, MD Professor         
Hôpital Archet 1 Recruiting
Nice, France, 06200
Contact: Laurence LEGROS, MD    33 4 92 03 58 44    Legros.l@chu-nice.fr   
Principal Investigator: Laurence LEGROS, MD         
Hôpital Haut-Lévêque Recruiting
Pessac, France, 33604
Contact: Krimo BOUABDALLAH, MD    33 (0) 5 57 65 65 11    krimo.bouabdallah@chu-bordeaux.fr   
Principal Investigator: Krimo BOUABDALLAH, MD         
CH Annecy Recruiting
Pringy, France, 74374
Contact: Pascal Cony-Makhoul, MD    33 4 50 63 64 31    pconymakhoul@ch-annecy.fr   
Principal Investigator: Pascal Cony-Makhoul, MD         
CHU Purpan Recruiting
Toulouse, France, 31059
Contact: Odile BEYNE-RAUZY, MD Professor    33 561 779 695    beynerauzy.o@chu_toulouse.fr   
Principal Investigator: Odile BEYNE-RAUZY, MD Professor         
Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire Recruiting
Tours, France, 37000
Contact: Emmanuel GYAN, MD    33 2 47 47 37 12    emmanuel.gyan@univ-tours.fr   
Principal Investigator: Emmanuel GYAN, MD         
Service d'hématologie et de médecine interne CHU de Nancy Hôpital de Brabois Recruiting
Vandoeuvre, France, 54511
Contact: Agnès-Paule GUERCI-BRESLER, MD    33 3 83 15 33 50    a.guerci@chu-nancy.fr   
Principal Investigator: Agnès-Paule GUERCI-BRESLER, MD         
Sponsors and Collaborators
Bioniche Pharma USA LLC
Investigators
Study Chair: Pierre FENAUX, MD Professor Service d'hématologie clinique- Hôpital Avicenne
Principal Investigator: Emmanuel GYAN, MD Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire-Hôpital Bretonneau
Principal Investigator: Agnès-Paule GUERCI-BRESLER, MD Service d'hématologie et de médecine interne-Hôpital de Brabois
Principal Investigator: Jean-Richard Eveillard, MD CHU de Brest- Hôpital Morvan
Principal Investigator: Odile BEYNE-RAUZY, MD Professor University Hospital, Toulouse
Principal Investigator: Laurence LEGROS, MD Hôpital Archet 1
Principal Investigator: Mauricette MICHALLET, MD Professor Hôpital Edouard Herriot
Principal Investigator: Krimo Bouabdallah, MD Hôpital Haut-Lévêque
Principal Investigator: Pascal Cony-Makhoul, MD CH Annecy
Principal Investigator: Manjesh Lingamurthy, MD Holy Cross Hospital
Principal Investigator: Steven Hager, MD California Cancer Associates
Principal Investigator: Misagh Karimi, MD Wilshire Oncology Medical Group
Principal Investigator: Veena Charu, MD Pacific Cancer Medical Center Inc.
  More Information

No publications provided

Responsible Party: Bioniche Pharma USA LLC
ClinicalTrials.gov Identifier: NCT01152346     History of Changes
Other Study ID Numbers: AZFAST101
Study First Received: June 25, 2010
Last Updated: September 10, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Bioniche Pharma USA LLC:
Bioequivalence
Myelodysplastic Syndrome
MDS
Azacitidine

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014