NCT02103478 · OUTCOME

Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1

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: GEOMETRIC_MEAN
Unit: ng*h/mL
Interval / dispersion: Geometric Coefficient of Variation
Time frame: Day 5

What was measured

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).

Analysis population: Participants who were successfully dosed according to criteria for both ASTX727 and IV decitabine dosing and with evaluable pharmacokinetic (PK) measurements are included.

Groups in this outcome

Phase 1 Dose Escalation Cohort 1

Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).

Phase 1 Dose Escalation Cohort 2

Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).

Phase 1 Dose Escalation Cohort 3

Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).

Phase 1 Dose Escalation Cohort 4

Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).

Phase 1 Dose Escalation Cohort 5

Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).

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 1 Dose Escalation Cohort 1	5
Phase 1 Dose Escalation Cohort 2	6
Phase 1 Dose Escalation Cohort 3	6
Phase 1 Dose Escalation Cohort 4	6
Phase 1 Dose Escalation Cohort 5	19

Reported measurements

Source class 1

Values in ng*h/mL · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Phase 1 Dose Escalation Cohort 1	53.6	40	Not reported	Not reported	Not reported
Phase 1 Dose Escalation Cohort 2	68.9	44	Not reported	Not reported	Not reported
Phase 1 Dose Escalation Cohort 3	94.8	46	Not reported	Not reported	Not reported
Phase 1 Dose Escalation Cohort 4	221	74	Not reported	Not reported	Not reported
Phase 1 Dose Escalation Cohort 5	146	50	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG000
spread
40
value
53.6
group Id
OG001
spread
44
value
68.9
group Id
OG002
spread
46
value
94.8
group Id
OG003
spread
74
value
221
group Id
OG004
spread
50
value
146

denoms

counts
group Id
OG000
value
5
group Id
OG001
value
6
group Id
OG002
value
6
group Id
OG003
value
6
group Id
OG004
value
19
units
Participants

description

dispersion Type

Geometric Coefficient of Variation

groups

description
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
id
OG000
title
Phase 1 Dose Escalation Cohort 1
description
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
id
OG001
title
Phase 1 Dose Escalation Cohort 2
description
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
id
OG002
title
Phase 1 Dose Escalation Cohort 3
description
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
id
OG003
title
Phase 1 Dose Escalation Cohort 4
description
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
id
OG004
title
Phase 1 Dose Escalation Cohort 5

param Type

GEOMETRIC_MEAN

population Description

Participants who were successfully dosed according to criteria for both ASTX727 and IV decitabine dosing and with evaluable pharmacokinetic (PK) measurements are included.

reporting Status

POSTED

time Frame

Day 5

title

Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1

type

PRIMARY

unit Of Measure

ng*h/mL

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Preserved source evidence · Not medical advice