TriangleNCT03306264 · OUTCOME
Total 5-day Area Under the Curve From 0 to 8 Hours (AUC0-8) 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
- 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 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 AUC0-8 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-8 (first ASTX727 dose) was added to (Day 2 AUC0-8 + Day 5 AUC0-8) × 2. Decitabine 5-day AUC0-8 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-8 + Day 5 AUC0-8) / 2 was multiplied by 5. If AUC0-8 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-8 on Day 5; the converse was also true.
Analysis population: Overall PK Analysis Set included participants who may not have been included in the Primary Endpoint PK Analysis Set and received any amount of study treatment, complied with the protocol sufficiently to ensure PK samples were collected as intended and provided sufficient samples to measure available plasma concentrations for decitabine. 'Overall number of participants analyzed' signifies those who were evaluable for this outcome measure.
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 | 124 |
| MDS or CMML: ASTX727 | 124 |
| AML: IV Decitabine | 70 |
| AML: ASTX727 | 70 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| MDS or CMML: IV Decitabine | 856.63 | 40.6 | Not reported | Not reported | Not reported |
| MDS or CMML: ASTX727 | 839.37 | 50.4 | Not reported | Not reported | Not reported |
| AML: IV Decitabine | 910.1 | 52.0 | Not reported | Not reported | Not reported |
| AML: ASTX727 | 883.8 | 52.1 | Not reported | Not reported | Not reported |
Source statistical analyses
- ci Lower Limit
- 91.74
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 104.5
- 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% CI of the 5-day AUC0-8 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
- 97.93
- ci Lower Limit
- 89.32
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 106.5
- 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 AUC0-8 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
- 97.55
Complete source fields
- analyses
- ci Lower Limit
- 91.74
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 104.5
- 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% CI of the 5-day AUC0-8 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
- 97.93
- ci Lower Limit
- 89.32
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 90
- ci Upper Limit
- 106.5
- 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 AUC0-8 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
- 97.55
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 40.6
- value
- 856.63
- group Id
- OG001
- spread
- 50.4
- value
- 839.37
- group Id
- OG002
- spread
- 52.0
- value
- 910.1
- group Id
- OG003
- spread
- 52.1
- value
- 883.8
- denoms
- counts
- group Id
- OG000
- value
- 124
- group Id
- OG001
- value
- 124
- group Id
- OG002
- value
- 70
- group Id
- OG003
- value
- 70
- units
- Participants
- description
- Total 5-day ASTX727 AUC0-8 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-8 (first ASTX727 dose) was added to (Day 2 AUC0-8 + Day 5 AUC0-8) × 2. Decitabine 5-day AUC0-8 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-8 + Day 5 AUC0-8) / 2 was multiplied by 5. If AUC0-8 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-8 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
- Overall PK Analysis Set included participants who may not have been included in the Primary Endpoint PK Analysis Set and received any amount of study treatment, complied with the protocol sufficiently to ensure PK samples were collected as intended and provided sufficient samples to measure available plasma concentrations for decitabine. 'Overall number of participants analyzed' signifies those who were evaluable for this outcome measure.
- reporting Status
- POSTED
- time Frame
- ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 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 8 Hours (AUC0-8) After Treatment With ASTX727 And IV Decitabine
- type
- SECONDARY
- unit Of Measure
- h*ng/mL
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Preserved source evidence · Not medical advice