Trial · NCT02103478
Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
NCT02103478, Phase 1, Phase 2, Completed, Astex Pharmaceuticals, Inc.; results first posted 2020-10-19
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS). Trials, record NCT02103478. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02103478
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
- NCT number
- NCT02103478
- Status
- Completed
- Phases
- Phase 1, Phase 2
- Enrollment
- 130 participants, actual
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Conditions
- Myelodysplastic Syndrome, MDS
- Interventions
- ASTX727 Dose Escalation, ASTX727 Dose Confirmation, ASTX727 Fixed-Dose Combination
- First posted
- 2014-04-04
- Last updated
- 2024-08-27
- Results first posted
- 2020-10-19
Source ClinicalTrials.gov
Registered outcomes19
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Day 5 | Mean AUC0-t of oral decitabine given with cedazuridine (E7727) following IV decitabine 20 mg/m\^2 infusion on Day 5. AUCs were calculated by the linear up/log down method using the measured concentration-time values above the BQL (below the limit of quantification). |
| Primary | Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2 | Pre-dose to Day 5 | Decitabine 5-day AUC ratio following IV decitabine 20 mg/m\^2 infusion versus concomitant oral administration of decitabine + cedazuridine (E7727) or ASTX727 in the dose combination and fixed-dose combination stages, respectively. AUC0-t (the area under the concentration-time curve from time zero to the time of the last (tlast) quantifiable concentration (Ct)) by dose/cohort and course/days was used for estimating decitabine cumulative 5-day AUC0-t exposures. |
| Primary | Number of Participants With Dose-limiting Toxicity in Phase 1 | Up to Day 28 in Course 1 (28 days per course) | Number of participants with protocol-specified dose-limiting toxicities (DLTs) in the dose escalation stage. DLTs were defined using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4.0), specifically ≥ Grade 3 non-hematologic toxicity (except Grade 3 nausea, vomiting, or diarrhea that is controllable by anti-emetics or optimal therapy or related to underlying disease or disease progression), specific Grade 3 laboratory tests, related prolonged Grade 4 thrombocytopenia or neutropenia that was not present prior to dosing, does not resolve within 14 days, and is not related to underlying disease, or any toxicity related to study treatment that results in treatment delays of \>4 weeks after Day 28. |
| Primary | Mean Maximum %LINE Demethylation in Phase 2 | Pre-dose to Day 28 in Course 2 (28 days per course) | Mean maximum % long interspread nuclear element-1 (LINE-1) demethylation after oral decitabine + cedazuridine (E7727) or ASTX727 (Course 1 or Course 2 - Treatment) compared with IV decitabine 20 mg/m\^2 (Course 1 or Course 2 - IV Decitabine) in the dose confirmation and fixed-dose combination stages, respectively. Least squares mean of maximum %LINE-1 methylation change from baseline. |
| Primary | Number of Participants With Overall Response in Phase 2 | Up to approximately 29 months | The evaluation of response was based on International Working Group (IWG) 2006 MDS Response Criteria, with overall response calculated as number of participants with complete response+partial response+marrow complete response+hematological improvement (CR+PR+mCR+HI). |
| Secondary | Area Under the Concentration Versus Time Curve of Cedazuridine (E7727) and Cedazuridine-epimer | At specified timepoints from 0 to 24 hours post-dose | AUC is a measure of the plasma concentration of the drug over time (AUC0-8). PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2. |
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Cedazuridine (E7727) and Cedazuridine-epimer | At specific timepoints from 0 to 24 hours post-dose | Cmax is the maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2. |
| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) of Cedazuridine (E7727) and Cedazuridine-epimer | At specific timepoints from 0 to 24 hours post-dose | Tmax is the time to maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and the dose confirmation and fixed-dose combination stages in Phase 2. |
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Decitabine | At specific timepoints from 0 to 24 hours post-dose | Cmax is the maximum observed plasma concentration. PK parameters for plasma decitabine are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2. |
| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) of Decitabine in Phase 2 | At specific timepoints from 0 to 24 hours post-dose | Tmax is the time to reach maximum plasma concentration for decitabine. PK parameters for plasma decitabine are reported for the dose confirmation and fixed-dose combination stages. |
1 to 10 of 19Source ClinicalTrials.gov
See all 19 registered outcomesOutcomes19
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Day 5 | Participants who were successfully dosed according to criteria for both ASTX727 and IV decitabine dosing and with evaluable pharmacokinetic (PK) measurements are included. | ng*h/mL | GEOMETRIC_MEAN |
| PRIMARY | Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2 | Pre-dose to Day 5 | Participants with evaluable PK measurements are included. Phase 2 crossover design was used to compare AUC ratio for oral and IV administration. | Ratio of Geometric LSM | GEOMETRIC_LEAST_SQUARES_MEAN |
| PRIMARY | Number of Participants With Dose-limiting Toxicity in Phase 1 | Up to Day 28 in Course 1 (28 days per course) | The safety population includes participants in Phase 1 who received at least one dose of study drug. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Mean Maximum %LINE Demethylation in Phase 2 | Pre-dose to Day 28 in Course 2 (28 days per course) | The pharmacodynamic population includes all participants with evaluable data who received at least one dose of investigational product. | Percent | LEAST_SQUARES_MEAN |
| PRIMARY | Number of Participants With Overall Response in Phase 2 | Up to approximately 29 months | The efficacy population includes all participants in Phase 2 who received at least one dose of investigational product. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Area Under the Concentration Versus Time Curve of Cedazuridine (E7727) and Cedazuridine-epimer | At specified timepoints from 0 to 24 hours post-dose | Participants with evaluable PK measurements are included. | ng*h/mL | GEOMETRIC_MEAN |
| SECONDARY | Maximum Observed Plasma Concentration (Cmax) of Cedazuridine (E7727) and Cedazuridine-epimer | At specific timepoints from 0 to 24 hours post-dose | Participants with evaluable PK measurements are included. | ng/mL | GEOMETRIC_MEAN |
| SECONDARY | Time to Maximum Observed Plasma Concentration (Tmax) of Cedazuridine (E7727) and Cedazuridine-epimer | At specific timepoints from 0 to 24 hours post-dose | Participants with evaluable PK measurements are included. | hours | MEDIAN |
| SECONDARY | Maximum Observed Plasma Concentration (Cmax) of Decitabine | At specific timepoints from 0 to 24 hours post-dose | Participants with evaluable PK measurements are included. | ng/mL | GEOMETRIC_MEAN |
| SECONDARY | Time to Maximum Observed Plasma Concentration (Tmax) of Decitabine in Phase 2 | At specific timepoints from 0 to 24 hours post-dose | Participants with evaluable PK measurements are included. | hours | MEDIAN |
1 to 10 of 19Source ClinicalTrials.gov
See all 19 outcomesResults by group158
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Phase 1 Dose Escalation Cohort 1 | 53.6 | Geometric Coefficient of Variation 40 | ng*h/mL | |
| Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Phase 1 Dose Escalation Cohort 2 | 68.9 | Geometric Coefficient of Variation 44 | ng*h/mL | |
| Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Phase 1 Dose Escalation Cohort 3 | 94.8 | Geometric Coefficient of Variation 46 | ng*h/mL | |
| Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Phase 1 Dose Escalation Cohort 4 | 221 | Geometric Coefficient of Variation 74 | ng*h/mL | |
| Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1 | Phase 1 Dose Escalation Cohort 5 | 146 | Geometric Coefficient of Variation 50 | ng*h/mL | |
| Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2 | Phase 2 Dose Confirmation | 93.52 | 80% Confidence Interval 82.10 to 106.50 | Ratio of Geometric LSM | |
| Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2 | Phase 2 Fixed-Dose Combination | 97.59 | 80% Confidence Interval 80.48 to 118.30 | Ratio of Geometric LSM | |
| Number of Participants With Dose-limiting Toxicity in Phase 1 | Phase 1 Dose Escalation Cohort 1 | 0 | Participants | ||
| Number of Participants With Dose-limiting Toxicity in Phase 1 | Phase 1 Dose Escalation Cohort 2 | 0 | Participants | ||
| Number of Participants With Dose-limiting Toxicity in Phase 1 | Phase 1 Dose Escalation Cohort 3 | 0 | Participants |
1 to 10 of 158Source ClinicalTrials.gov
See all 158 results by groupParticipant flow27
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Phase 1 Dose Escalation Cohort 1 | 7 | |
| Overall Study | STARTED | Phase 1 Dose Escalation Cohort 2 | 6 | |
| Overall Study | STARTED | Phase 1 Dose Escalation Cohort 3 | 6 | |
| Overall Study | STARTED | Phase 1 Dose Escalation Cohort 4 | 6 | |
| Overall Study | STARTED | Phase 1 Dose Escalation Cohort 5 | 19 | |
| Overall Study | STARTED | Phase 2 Dose Confirmation Sequence A | 25 | |
| Overall Study | STARTED | Phase 2 Dose Confirmation Sequence B | 25 | |
| Overall Study | STARTED | Phase 2 Fixed-Dose Combination Sequence A | 16 | |
| Overall Study | STARTED | Phase 2 Fixed-Dose Combination Sequence B | 14 | |
| Overall Study | COMPLETED | Phase 1 Dose Escalation Cohort 1 | 0 |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 participant flowAdverse events2,093
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 1 | 4 | 7 | 16 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 2 | 3 | 6 | 4 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 3 | 4 | 6 | 11 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 4 | 3 | 6 | 7 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 5 | 10 | 19 | 34 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 2 Dose Confirmation | 27 | 50 | 67 |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Phase 2 Fixed-Dose Combination | 15 | 30 | 59 |
| other | Neutropenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 1 | 3 | 7 | 13 |
| other | Neutropenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 2 | 2 | 6 | 12 |
| other | Neutropenia | Blood and lymphatic system disorders | Phase 1 Dose Escalation Cohort 3 | 4 | 6 | 4 |
1 to 10 of 2,093Source ClinicalTrials.gov
See all 2,093 adverse eventsAdverse event totals21
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Phase 1 Dose Escalation Cohort 1 | 2 | 7 |
| Total, all-cause mortality | Phase 1 Dose Escalation Cohort 2 | 2 | 6 |
| Total, all-cause mortality | Phase 1 Dose Escalation Cohort 3 | 1 | 6 |
| Total, all-cause mortality | Phase 1 Dose Escalation Cohort 4 | 1 | 6 |
| Total, all-cause mortality | Phase 1 Dose Escalation Cohort 5 | 5 | 19 |
| Total, all-cause mortality | Phase 2 Dose Confirmation | 29 | 50 |
| Total, all-cause mortality | Phase 2 Fixed-Dose Combination | 21 | 30 |
| Total, other adverse events | Phase 1 Dose Escalation Cohort 1 | 6 | 7 |
| Total, other adverse events | Phase 1 Dose Escalation Cohort 2 | 6 | 6 |
| Total, other adverse events | Phase 1 Dose Escalation Cohort 3 | 6 | 6 |
1 to 10 of 21Source ClinicalTrials.gov
See all 21 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons1
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison |
|---|
| Phase 2 Dose Confirmation vs Phase 2 Fixed-Dose Combination: Number of Participants With Overall Response in Phase 2 |
Source Trial comparisons
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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