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

NCT01152346 | Completed Phase 1

• 1 other identifier: AZFAST101
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Myelodysplastic Syndrome

Keywords

Bioequivalence; Myelodysplastic Syndrome; MDS; Azacitidine

Outcome Measures

Primary Outcomes (1)

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

  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.

  13 timepoints from pre-dose to 8 hours post dose

Secondary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Throughout study

Study Arms (2)

ARM 1

OTHER

Sequence- Azacitidine followed by Vidaza®

Drug: Azacitidine for Injection; Drug: Vidaza®

ARM 2

OTHER

Sequence-Vidaza® followed by Azacitidine

Drug: Azacitidine for Injection; Drug: Vidaza®

Interventions

Azacitidine for Injection DRUG

75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment

ARM 1; ARM 2

Vidaza® DRUG

75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment

ARM 1; ARM 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioniche Pharma USA LLC: lead

Study Sites (13)

Pacific Cancer Medical Center Inc.

Anaheim, California, 92801, United States

Location

Wilshire Oncology Medical Group

Corona, California, 92879, United States

Location

California Cancer Associates

Fresno, California, 93720, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Service d'hématologie clinique Hôpital Avicenne

Bobigny, 93009, France

Location

CHU de Brest- Hôpital Morvan

Brest, 29609, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Hôpital Archet 1

Nice, 06200, France

Location

Hôpital Haut-Lévêque

Pessac, 33604, France

Location

CH Annecy

Pringy, 74374, France

Location

CHU Purpan

Toulouse, 31059, France

Location

Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire

Tours, 37000, France

Location

Service d'hématologie et de médecine interne CHU de Nancy Hôpital de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine; Injections

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Pierre FENAUX, MD Professor

  Service d'hématologie clinique- Hôpital Avicenne

  STUDY CHAIR

• 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.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2010
• First Posted: June 29, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2013
• Last Updated: January 28, 2015

Record last verified: 2015-01

Locations

FR (9); US (4)