TriangleNCT03306264 · OUTCOME
Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- GEOMETRIC_MEAN
- Unit
- hours*nanograms per milliliter (h*ng/mL)
- Interval / dispersion
- Geometric Coefficient of Variation
- Time frame
- ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
What was measured
Total 5-day ASTX727 AUC0-24 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-24 (first ASTX727 dose) was added to (Day 2 AUC0-24+ Day 5 AUC0-24) × 2. Decitabine 5-day AUC0-24 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-24+ Day 5 AUC0-24) / 2 was multiplied by 5. If AUC0-24 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-24 on Day 5; the converse was also true.
Analysis population: Primary Endpoint Pharmacokinetics (PK) Analysis Set included participants who received full dose of ASTX727 within 3 hours of the intended dosing time, and no vomiting within 6 hours of dosing, and had at least 2 days of evaluable decitabine (AUC0-24) measurements in the ASTX727 cycle, i.e, Day 1 and either Day 2 or Day 5 and received the full IV decitabine dose as a 1-hour infusion.
Groups in this outcome
MDS or CMML: IV Decitabine
Participants with MDS or CMML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle=28 days).
MDS or CMML: ASTX727
Participants with MDS or CMML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle = 28 days). From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
AML: IV Decitabine
Participants with AML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle=28 days).
AML: ASTX727
Participants with AML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle = 28 days). From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
| Group | Source count |
|---|---|
| MDS or CMML: IV Decitabine | 123 |
| MDS or CMML: ASTX727 | 123 |
| AML: IV Decitabine | 69 |
| AML: ASTX727 | 69 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| MDS or CMML: IV Decitabine | 864.34 | 40.0 | Not reported | Not reported | Not reported |
| MDS or CMML: ASTX727 | 855.96 | 50.6 | Not reported | Not reported | Not reported |
| AML: IV Decitabine | 910.1 | 52.4 | Not reported | Not reported | Not reported |
| AML: ASTX727 | 900.5 | 52.0 | Not reported | Not reported | Not reported |
Source statistical analyses
- ci Lower Limit
- 92.66
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 105.6
- estimate Comment
- Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
- group Description
- MDS or CMML: IV Decitabine Versus MDS or CMML: ASTX727
- group Ids
- OG000
- OG001
- non Inferiority Comment
- ASTX727 and IV decitabine were to be considered equivalent if the 2-sided 90% confidence interval (CI) of the 5-day AUC0-24 ratio of Least Square Mean (LSM) for oral/IV was contained entirely within the range of 0.80 - 1.25.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Ratio of Geometric LSM
- param Value
- 98.93
- ci Lower Limit
- 91.23
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 108.8
- estimate Comment
- Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
- group Description
- AML: IV Decitabine Versus AML: ASTX727
- group Ids
- OG002
- OG003
- non Inferiority Comment
- ASTX727 and IV decitabine were to be considered equivalent if the 2-sided 90% CI of the 5-day AUC0-24 ratio of LSM for oral/IV was contained entirely within the range of 0.80 - 1.25.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Ratio of Geometric LSM
- param Value
- 99.64
Complete source fields
- analyses
- ci Lower Limit
- 92.66
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 105.6
- estimate Comment
- Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
- group Description
- MDS or CMML: IV Decitabine Versus MDS or CMML: ASTX727
- group Ids
- OG000
- OG001
- non Inferiority Comment
- ASTX727 and IV decitabine were to be considered equivalent if the 2-sided 90% confidence interval (CI) of the 5-day AUC0-24 ratio of Least Square Mean (LSM) for oral/IV was contained entirely within the range of 0.80 - 1.25.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Ratio of Geometric LSM
- param Value
- 98.93
- ci Lower Limit
- 91.23
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 108.8
- estimate Comment
- Analysis was based on ANOVA model with treatment, cycle, and sequence as fixed effects, and participant nested in sequence as a random effect (ratio is Oral/IV).
- group Description
- AML: IV Decitabine Versus AML: ASTX727
- group Ids
- OG002
- OG003
- non Inferiority Comment
- ASTX727 and IV decitabine were to be considered equivalent if the 2-sided 90% CI of the 5-day AUC0-24 ratio of LSM for oral/IV was contained entirely within the range of 0.80 - 1.25.
- non Inferiority Type
- EQUIVALENCE
- param Type
- Ratio of Geometric LSM
- param Value
- 99.64
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 40.0
- value
- 864.34
- group Id
- OG001
- spread
- 50.6
- value
- 855.96
- group Id
- OG002
- spread
- 52.4
- value
- 910.1
- group Id
- OG003
- spread
- 52.0
- value
- 900.5
- denoms
- counts
- group Id
- OG000
- value
- 123
- group Id
- OG001
- value
- 123
- group Id
- OG002
- value
- 69
- group Id
- OG003
- value
- 69
- units
- Participants
- description
- Total 5-day ASTX727 AUC0-24 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-24 (first ASTX727 dose) was added to (Day 2 AUC0-24+ Day 5 AUC0-24) × 2. Decitabine 5-day AUC0-24 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-24+ Day 5 AUC0-24) / 2 was multiplied by 5. If AUC0-24 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-24 on Day 5; the converse was also true.
- dispersion Type
- Geometric Coefficient of Variation
- groups
- description
- Participants with MDS or CMML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle=28 days).
- id
- OG000
- title
- MDS or CMML: IV Decitabine
- description
- Participants with MDS or CMML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle = 28 days). From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
- id
- OG001
- title
- MDS or CMML: ASTX727
- description
- Participants with AML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle=28 days).
- id
- OG002
- title
- AML: IV Decitabine
- description
- Participants with AML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycles 1 or 2 (each cycle = 28 days). From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
- id
- OG003
- title
- AML: ASTX727
- param Type
- GEOMETRIC_MEAN
- population Description
- Primary Endpoint Pharmacokinetics (PK) Analysis Set included participants who received full dose of ASTX727 within 3 hours of the intended dosing time, and no vomiting within 6 hours of dosing, and had at least 2 days of evaluable decitabine (AUC0-24) measurements in the ASTX727 cycle, i.e, Day 1 and either Day 2 or Day 5 and received the full IV decitabine dose as a 1-hour infusion.
- reporting Status
- POSTED
- time Frame
- ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
- title
- Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine
- type
- PRIMARY
- unit Of Measure
- hours*nanograms per milliliter (h*ng/mL)
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Preserved source evidence · Not medical advice