Myelodysplastic SyndromesPhase 1NCT01519011
Study to Evaluate Pharmacokinetics, Food Effect, Safety and Efficacy of Oral Azacitidine
A Phase 1 study testing oral azacitidine in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Celgene at 8 sites in United States.
Trial summary
The primary purpose of this study is to evaluate the pharmacokinetics of oral azacitidine when administered once daily as two 150-mg tablets, including the effect of food, and to evaluate the bioavailability of oral azacitidine 300-mg when administered as two 150-mg tablets relative to three 100-mg tablets. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
- What is being tested?
- oral azacitidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 8 sitesUnited States
- Study dates
- 7 Feb 2012to 12 May 2015
- 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
- Age 18 years or older at the time of signing the informed consent document
- Diagnosis of Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- At least 3 month life expectancy
- Adequate organ function, defined as:
- Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
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- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the ULN;
- Serum creatinine ≤ 1.5 times the ULN;
- Serum bicarbonate ≥ 20 mEq/L
- Females of childbearing potential (FCBP) must:
- Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following the last dose of oral azacitidine; and
- Have a negative serum or urine pregnancy test (investigator's discretion; sensitivity of at least 25 mIU/mL) at screening; and
- Have a negative serum or urine pregnancy test (investigator's discretion; sensitivity of at least 25 mIU/mL) within 72 hours prior to Day 1 of the pharmacokinetic (PK) phase (note that the screening pregnancy test can be used as the test prior to Day 1 of the PK phase if it is performed within the 72 hour timeframe).
- Males with partners who are FCBP must agree that they and their partners will use at least two effective contraceptive methods throughout the study and will avoid fathering a child for 3 months following the date of last oral azacitidine dosing
- Understand and voluntarily sign an informed consent document prior to the start of any study related assessments/procedures
- Able to adhere to the study visit schedule and other protocol requirements
Who cannot join
- Suspected or proven acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
- Previous treatment with azacitidine or other demethylating agents within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
- Anticancer therapy (standard or investigational) within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
- Use of any proton pump inhibitor or any other agent that may affect gastric acid level within 28 days prior to study therapy (only applicable to Part II of the PK phase)
- Concurrent use of erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, except that the subject is on a stable dose for at least 4 weeks (28 days) prior to starting study therapy
- Concurrent use of iron-chelating agents, except that the subject is on a stable dose for at least 8 weeks (56 days) prior to starting study therapy
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- Concurrent corticosteroid use, except for medical conditions other than Myelodysplastic Syndrome and provided the subject is on a stable or decreasing dose for ≥ 1 week prior to start study therapy
- Pregnant or lactating females
- Any known or suspected hypersensitivity to azacitidine or mannitol or any other ingredient used in the manufacture of oral azacitidine (see the azacitidine IB)
- Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
- Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C
- Presence of gastrointestinal disease, malignant hepatic tumors, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
- Current congestive heart failure (New York Heart Association Class III-IV Appendix G), unstable angina or angina requiring surgical or medical intervention within 6 months prior to starting study therapy, myocardial infarct within 6 months prior to starting study therapy, or uncontrolled cardiac arrhythmia (defined as arrhythmia that is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia). Subjects with controlled atrial fibrillation that is asymptomatic are eligible
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Any condition that confounds the ability to interpret data from the study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Cincinnati Physician's Inc.
Cincinnati, Ohio, 45267-0562
Texas Oncology
Dallas, Texas, 75230
Rocky Mountain Cancer Center
Denver, Colorado, 80218-1210
Moores UCSD Cancer Center MC-0987
La Jolla, California, 92093
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Virginia Oncology Associates
Norfolk, Virginia, 23502
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
About this study
Official title: A PHASE 1, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS AND EFFECT OF FOOD OF A NEW TABLET FORMULATION OF ORAL AZACITIDINE, AND TO EVALUATE THE SAFETY AND EFFICACY OF ORAL AZACITIDINE IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES, CHRONIC MYELOMONOCYTIC LEUKEMIA OR ACUTE MYELOID LEUKEMIA
The primary purpose of this study is to evaluate the pharmacokinetics of oral azacitidine when administered once daily as two 150-mg tablets, including the effect of food, and to evaluate the bioavailability of oral azacitidine 300-mg when administered as two 150-mg tablets relative to three 100-mg tablets.
- Being tested
- oral azacitidine
- Keywords
- Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Vidaza, oral azacitidine, aza, oral aza, pharmacokinetics, hematology, myeloid disease, PK
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral azacitidineDrug
oral azacitidine 300-mg once daily for 3 total doses with two 150-mg tablets (fasted and fed) or three 100-mg tablets (fasted).
oral azacitidineDrug
300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 1: A, B, C | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| 2: B, C, A | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| 3: C, A, B | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| 4: B, A, C | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| 5: A, C, B | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| 6: C, B, A | Experimental | Dose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition.
Dose C: Single oral administration with two 150-mg tablets under fed condition. Receives: Drug: oral azacitidine |
| Extension | Experimental | 300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle. Receives: Drug: oral azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK-(AUC)
PK-Area under the plasma concentration time curve (AUC)
Measured: Up to 10 days
PK-(T½)
PK-Terminal half-life (T½)
Measured: Up to 10 days
PK-(Cmax)
Observed maximum concentration in plasma (Cmax)
Measured: Up to 10 days
PK-(Tmax)
PK-Time to maximum plasma concentration (Tmax)
Measured: Up to 10 days
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine.
Measured: Up to 10 days
Secondary outcomes (4)
Adverse Events
Number of participants with adverse events
Measured: Up to 2 years
Hematological response/improvement
Proportion of subjects achieving hematological response/improvement
Measured: Up to 2 years
Transfusion independence
Proportion of subjects achieving RBC transfusion independence
Measured: Up to 2 years
Platelet transfusion independence
Proportion of subjects achieving platelet transfusion independence
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study start7 Feb 2012
- Primary completion31 Dec 2012
- Study completion12 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Barry Skikne, M.D., Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01519011
- Sponsor's protocol ID
- AZA-MDS-004
- Other IDs
- T-AZA-006
- Status last verified
- Nov 2019
- First submitted
- 24 Jan 2012
- Last updated
- 12 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J Clin Pharmacol. 2014 Jun;54(6):630-9. doi: 10.1002/jcph.251. Epub 2014 Jan 18.
PubMed 24374798Savona MR, Kolibaba K, Conkling P, Kingsley EC, Becerra C, Morris JC, Rifkin RM, Laille E, Kellerman A, Ukrainskyj SM, Dong Q, Skikne BS. Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. Am J Hematol. 2018 Oct;93(10):1199-1206. doi: 10.1002/ajh.25216. Epub 2018 Sep 3.
PubMed 30016552
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS AND EFFECT OF FOOD OF A NEW TABLET FORMULATION OF ORAL AZACITIDINE, AND TO EVALUATE THE SAFETY AND EFFICACY OF ORAL AZACITIDINE IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES, CHRONIC MYELOMONOCYTIC LEUKEMIA OR ACUTE MYELOID LEUKEMIA
- ClinicalTrials.gov ID
- NCT01519011
- Acronym / sponsor ID
- AZA-MDS-004
- Keywords
- Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Vidaza, oral azacitidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 7 Feb 2012 (actual)
- Primary completion
- 31 Dec 2012 (actual)
- Study completion
- 12 May 2015 (actual)
- First posted
- 26 Jan 2012 (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 primary purpose of this study is to evaluate the pharmacokinetics of oral azacitidine when administered once daily as two 150-mg tablets, including the effect of food, and to evaluate the bioavailability of oral azacitidine 300-mg when administered as two 150-mg tablets relative to three 100-mg tablets.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1: A, B, C | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| 2: B, C, A | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| 3: C, A, B | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| 4: B, A, C | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| 5: A, C, B | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| 6: C, B, A | Experimental | Drug: oral azacitidineDose A: Single oral administration with three 100-mg tablets under fasted condition Dose B: Single oral administration with two 150-mg tablets under fasted condition. Dose C: Single oral administration with two 150-mg tablets under fed condition. |
| Extension | Experimental | Drug: oral azacitidine300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age 18 years or older at the time of signing the informed consent document
- Diagnosis of Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- At least 3 month life expectancy
- Adequate organ function, defined as:
Key exclusion criteria (16 listed)
- Suspected or proven acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
- Previous treatment with azacitidine or other demethylating agents within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
- Anticancer therapy (standard or investigational) within 21 days prior to starting study therapy or ongoing adverse events from previous treatment, regardless of the time period
- Use of any proton pump inhibitor or any other agent that may affect gastric acid level within 28 days prior to study therapy (only applicable to Part II of the PK phase)
- Concurrent use of erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, except that the subject is on a stable dose for at least 4 weeks (28 days) prior to starting study therapy
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 |
|---|---|---|
| oral azacitidineoral azacitidine 300-mg once daily for 3 total doses with two 150-mg tablets (fasted and fed) or three 100-mg tablets (fasted). | Drug | 1: A, B, C, 2: B, C, A, 3: C, A, B, 4: B, A, C, 5: A, C, B, 6: C, B, A |
| oral azacitidine300-mg (three 100-mg tablets) once daily for 21 days of a 28-day cycle. | Drug | Extension |
Primary outcome
PK-(AUC)
Time frame: Up to 10 days
PK-Area under the plasma concentration time curve (AUC)
PK-(T½)
Time frame: Up to 10 days
PK-Terminal half-life (T½)
PK-(Cmax)
Time frame: Up to 10 days
Observed maximum concentration in plasma (Cmax)
PK-(Tmax)
Time frame: Up to 10 days
PK-Time to maximum plasma concentration (Tmax)
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine
Time frame: Up to 10 days
To evaluate the effect of gastric acid pH modulation, through a proton pump inhibitor, on the PK of oral azacitidine.
4 secondary outcomes
Adverse Events
Time frame: Up to 2 years
Hematological response/improvement
Time frame: Up to 2 years
Transfusion independence
Time frame: Up to 2 years
Platelet transfusion independence
Time frame: Up to 2 years
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 12 Nov 2019.
- Background: PubMed 24374798Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J Clin Pharmacol. 2014 Jun;54(6):630-9. doi: 10.1002/jcph.251. Epub 2014 Jan 18.
- Background: PubMed 30016552Savona MR, Kolibaba K, Conkling P, Kingsley EC, Becerra C, Morris JC, Rifkin RM, Laille E, Kellerman A, Ukrainskyj SM, Dong Q, Skikne BS. Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. Am J Hematol. 2018 Oct;93(10):1199-1206. doi: 10.1002/ajh.25216. Epub 2018 Sep 3.
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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.
Barry Skikne, M.D. study director
Celgene
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing oral azacitidine in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Celgene at 8 sites in United States.
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 16 inclusion and 16 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 12 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in 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?
PK-(AUC) (time frame: Up to 10 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01519011, which also lists 2 linked publications.
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 12 Nov 2019.