Myelodysplastic SyndromePhase 1NCT01152346
Bioequivalence Study of Azacitidine for Injection in Myelodysplastic Syndrome (MDS) Patients
A Phase 1 study testing Azacitidine for Injection and Vidaza® in people with Myelodysplastic Syndrome, run by Bioniche Pharma USA LLC at 13 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Azacitidine for Injection and Vidaza®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 13 sitesin 2 countries
- Study dates
- Apr 2011to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
France9 sites
Service d'hématologie clinique Hôpital Avicenne
Bobigny, 93009
CHU de Brest- Hôpital Morvan
Brest, 29609
Centre Hospitalier Lyon Sud
Lyon, 69495
Hôpital Archet 1
Nice, 06200
Hôpital Haut-Lévêque
Pessac, 33604
CH Annecy
Pringy, 74374
CHU Purpan
Toulouse, 31059
Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire
Tours, 37000
Service d'hématologie et de médecine interne CHU de Nancy Hôpital de Brabois
Vandœuvre-lès-Nancy, 54511
United States4 sites
Pacific Cancer Medical Center Inc.
Anaheim, California, 92801
Wilshire Oncology Medical Group
Corona, California, 92879
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
California Cancer Associates
Fresno, California, 93720
About this study
Official title: A Multi-Center Relative Bioavailability Study of Azacitidine 75 mg/m2 Subcutaneous Injection In Myelodysplastic Syndrome Patients Under Fasting Conditions
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.
Read the 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.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Azacitidine for Injection, Vidaza®
- Keywords
- Bioequivalence, Myelodysplastic Syndrome, MDS, Azacitidine
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azacitidine for InjectionDrug
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment
Vidaza®Drug
75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment
| Study group | Role | What they receive |
|---|---|---|
| ARM 1 | Other | Sequence- Azacitidine followed by Vidaza® Receives: Drug: Azacitidine for Injection; Drug: Vidaza® |
| ARM 2 | Other | Sequence-Vidaza® followed by Azacitidine Receives: Drug: Azacitidine for Injection; Drug: Vidaza® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Safety will be assessed through monitoring of adverse events and laboratory measures.
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2010 (estimated)
- Study startApr 2011
- Primary completionDec 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bioniche Pharma USA LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pierre FENAUX, MD Professor, Study chair, Service d'hématologie clinique- Hôpital AvicenneEmmanuel GYAN, MD, Principal investigator, Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire-Hôpital BretonneauAgnès-Paule GUERCI-BRESLER, MD, Principal investigator, Service d'hématologie et de médecine interne-Hôpital de BraboisJean-Richard Eveillard, MD, Principal investigator, CHU de Brest- Hôpital MorvanOdile BEYNE-RAUZY, MD Professor, Principal investigator, University Hospital, ToulouseLaurence LEGROS, MD, Principal investigator, Hôpital Archet 1Mauricette MICHALLET, MD Professor, Principal investigator, Hôpital Edouard HerriotKrimo Bouabdallah, MD, Principal investigator, Hôpital Haut-Lévêque
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01152346
- Sponsor's protocol ID
- AZFAST101
- Status last verified
- Jan 2015
- First submitted
- 25 Jun 2010
- Last updated
- 28 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Relative Bioavailability Study of Azacitidine 75 mg/m2 Subcutaneous Injection In Myelodysplastic Syndrome Patients Under Fasting Conditions
- ClinicalTrials.gov ID
- NCT01152346
- Acronym / sponsor ID
- AZFAST101
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Bioequivalence, Myelodysplastic Syndrome, MDS, Azacitidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Bioniche Pharma USA LLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 29 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM 1 | Other | Drug: Azacitidine for Injection, Drug: Vidaza®Sequence- Azacitidine followed by Vidaza® |
| ARM 2 | Other | Drug: Azacitidine for Injection, Drug: Vidaza®Sequence-Vidaza® followed by Azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azacitidine for Injection75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment | Drug | ARM 1, ARM 2 |
| Vidaza®75 mg/m2 sc injection on Day 1 of either cycle 1 or cycle 2 per randomization assignment | Drug | ARM 1, ARM 2 |
Primary outcome
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
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.
1 secondary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre FENAUX, MD Professor study chair
Service d'hématologie clinique- Hôpital Avicenne
Emmanuel GYAN, MD principal investigator
Centre régional de cancérologie Henry-Kaplan Service d'Hématologie et thérapie cellulaire-Hôpital Bretonneau
Agnès-Paule GUERCI-BRESLER, MD principal investigator
Service d'hématologie et de médecine interne-Hôpital de Brabois
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine for Injection and Vidaza® in people with Myelodysplastic Syndrome, run by Bioniche Pharma USA LLC at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2015.