NCT02103478 · OUTCOME
Mean Maximum %LINE Demethylation in Phase 2
Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS) · Source last updated 2024-08-27
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- LEAST_SQUARES_MEAN
- Unit
- Percent
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- Pre-dose to Day 28 in Course 2 (28 days per course)
What was measured
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.
Analysis population: The pharmacodynamic population includes all participants with evaluable data who received at least one dose of investigational product.
Groups in this outcome
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.
Analysis denominator · Participants
| Group | Source count |
|---|
| Phase 2 Dose Confirmation | 48 |
|---|
| Phase 2 Fixed-Dose Combination | 30 |
|---|
Reported measurements
Course 1 - Treatment
Analysis denominator · Participants
| Group | Source count |
|---|
| Phase 2 Dose Confirmation | 24 |
|---|
| Phase 2 Fixed-Dose Combination | 16 |
|---|
Values in Percent · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Phase 2 Dose Confirmation | 11.159 | Not reported | 9.023 | 13.294 | Not reported |
|---|
| Phase 2 Fixed-Dose Combination | 10.077 | Not reported | 7.696 | 12.459 | Not reported |
|---|
Course 1 - IV Decitabine
Analysis denominator · Participants
| Group | Source count |
|---|
| Phase 2 Dose Confirmation | 24 |
|---|
| Phase 2 Fixed-Dose Combination | 14 |
|---|
Values in Percent · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Phase 2 Dose Confirmation | 11.303 | Not reported | 9.167 | 13.439 | Not reported |
|---|
| Phase 2 Fixed-Dose Combination | 12.665 | Not reported | 10.12 | 15.211 | Not reported |
|---|
Course 2 - Treatment
Analysis denominator · Participants
| Group | Source count |
|---|
| Phase 2 Dose Confirmation | 22 |
|---|
| Phase 2 Fixed-Dose Combination | 9 |
|---|
Values in Percent · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Phase 2 Dose Confirmation | 9.833 | Not reported | 7.446 | 12.219 | Not reported |
|---|
| Phase 2 Fixed-Dose Combination | 8.134 | Not reported | 4.438 | 11.830 | Not reported |
|---|
Course 2 - IV Decitabine
Analysis denominator · Participants
| Group | Source count |
|---|
| Phase 2 Dose Confirmation | 22 |
|---|
| Phase 2 Fixed-Dose Combination | 11 |
|---|
Values in Percent · Interval/dispersion: 95% Confidence Interval| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Phase 2 Dose Confirmation | 9.920 | Not reported | 7.534 | 12.307 | Not reported |
|---|
| Phase 2 Fixed-Dose Combination | 8.230 | Not reported | 4.887 | 11.574 | Not reported |
|---|
Source statistical analyses
Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.
- ci Lower Limit
- -3.165
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 2.876
- estimate Comment
- Course 1
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.144
- ci Lower Limit
- -3.463
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 3.288
- estimate Comment
- Course 2
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.087
- ci Lower Limit
- -6.074
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.899
- estimate Comment
- Course 1
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -2.588
- ci Lower Limit
- -5.080
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 4.888
- estimate Comment
- Course 2
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.096
Complete source fields
- analyses
- ci Lower Limit
- -3.165
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 2.876
- estimate Comment
- Course 1
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.144
- ci Lower Limit
- -3.463
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 3.288
- estimate Comment
- Course 2
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.087
- ci Lower Limit
- -6.074
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.899
- estimate Comment
- Course 1
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -2.588
- ci Lower Limit
- -5.080
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 4.888
- estimate Comment
- Course 2
- non Inferiority Comment
- The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Mean Difference (Final Values)
- param Value
- -0.096
- classes
- categories
- measurements
- group Id
- OG000
- lower Limit
- 9.023
- upper Limit
- 13.294
- value
- 11.159
- group Id
- OG001
- lower Limit
- 7.696
- upper Limit
- 12.459
- value
- 10.077
- denoms
- counts
- group Id
- OG000
- value
- 24
- group Id
- OG001
- value
- 16
- units
- Participants
- title
- Course 1 - Treatment
- categories
- measurements
- group Id
- OG000
- lower Limit
- 9.167
- upper Limit
- 13.439
- value
- 11.303
- group Id
- OG001
- lower Limit
- 10.12
- upper Limit
- 15.211
- value
- 12.665
- denoms
- counts
- group Id
- OG000
- value
- 24
- group Id
- OG001
- value
- 14
- units
- Participants
- title
- Course 1 - IV Decitabine
- categories
- measurements
- group Id
- OG000
- lower Limit
- 7.446
- upper Limit
- 12.219
- value
- 9.833
- group Id
- OG001
- lower Limit
- 4.438
- upper Limit
- 11.830
- value
- 8.134
- denoms
- counts
- group Id
- OG000
- value
- 22
- group Id
- OG001
- value
- 9
- units
- Participants
- title
- Course 2 - Treatment
- categories
- measurements
- group Id
- OG000
- lower Limit
- 7.534
- upper Limit
- 12.307
- value
- 9.920
- group Id
- OG001
- lower Limit
- 4.887
- upper Limit
- 11.574
- value
- 8.230
- denoms
- counts
- group Id
- OG000
- value
- 22
- group Id
- OG001
- value
- 11
- units
- Participants
- title
- Course 2 - IV Decitabine
- denoms
- counts
- group Id
- OG000
- value
- 48
- group Id
- OG001
- value
- 30
- units
- Participants
- description
- 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.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
- id
- OG000
- title
- Phase 2 Dose Confirmation
- description
- Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
- id
- OG001
- title
- Phase 2 Fixed-Dose Combination
- param Type
- LEAST_SQUARES_MEAN
- population Description
- The pharmacodynamic population includes all participants with evaluable data who received at least one dose of investigational product.
- reporting Status
- POSTED
- time Frame
- Pre-dose to Day 28 in Course 2 (28 days per course)
- title
- Mean Maximum %LINE Demethylation in Phase 2
- type
- PRIMARY
- unit Of Measure
- Percent
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