NCT03922100 · OUTCOME

Pharmacokinetic Parameters: Accumulation Ratios (RA) for AUC0-24 and Cmax

Study of NMS-03592088 in Patients With Relapsed or Refractory AML or CMML · Source last updated 2026-03-18

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: MEAN
Unit: Ratio
Interval / dispersion: Standard Deviation
Time frame: Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.

What was measured

Plasma samples were collected and used for pharmacokinetics assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%).

Analysis population: Participants evaluable for PK analysis (treated participants were considered evaluable if they had sufficient baseline and on-study sampled material to provide interpretable results). The plasma PK of NMS-03592088 and 2 metabolites NMS-03593860 and NMS-03603422 were collected, and PK profile characterised. Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.

Groups in this outcome

Phase 1, Schedule A: 20 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.

Phase 1, Schedule A: 40 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 40 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 80 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 80 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 120 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 180 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 270 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 270 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 300 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 300 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule A: 360 mg

All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 360 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle

Phase 1, Schedule B: 120 mg

All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.

Phase 1, Schedule B: 180 mg

All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.

Phase 1, Schedule B: 250 mg

All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 250 mg administered orally once daily for 28 consecutive days, in a 28-day cycle

Phase 2, Schedule B:360+150 mg

Participants who had failed standard of care including Venetoclax and Gilteritining based therapies. NMS-03592088 was administered, on Cycle 1, at 360 mg/day (loading dose) for 5 consecutive days, followed by 150 mg/day (maintenance dose) for 23 consecutive days. The same maintenance dose (150 mg/day) was administered from Cycle 2 onwards

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, Schedule A: 20 mg	3
Phase 1, Schedule A: 40 mg	3
Phase 1, Schedule A: 80 mg	3
Phase 1, Schedule A: 120 mg	3
Phase 1, Schedule A: 180 mg	3
Phase 1, Schedule A: 270 mg	4
Phase 1, Schedule A: 300 mg	10
Phase 1, Schedule A: 360 mg	3
Phase 1, Schedule B: 120 mg	4
Phase 1, Schedule B: 180 mg	6
Phase 1, Schedule B: 250 mg	4
Phase 2, Schedule B:360+150 mg	15

Reported measurements

RA, AUC0-24: Day 21

Analysis denominator · Participants

Group	Source count
Phase 1, Schedule A: 20 mg	3
Phase 1, Schedule A: 40 mg	3
Phase 1, Schedule A: 80 mg	3
Phase 1, Schedule A: 120 mg	3
Phase 1, Schedule A: 180 mg	3
Phase 1, Schedule A: 270 mg	4
Phase 1, Schedule A: 300 mg	10
Phase 1, Schedule A: 360 mg	3
Phase 1, Schedule B: 120 mg	0
Phase 1, Schedule B: 180 mg	0
Phase 1, Schedule B: 250 mg	0
Phase 2, Schedule B:360+150 mg	0

Values in Ratio · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Phase 1, Schedule A: 20 mg	8.99	46.9	Not reported	Not reported	Not reported
Phase 1, Schedule A: 40 mg	3.72	26.0	Not reported	Not reported	Not reported
Phase 1, Schedule A: 80 mg	4.42	18.3	Not reported	Not reported	Not reported
Phase 1, Schedule A: 120 mg	3.91	9.88	Not reported	Not reported	Not reported
Phase 1, Schedule A: 180 mg	4.14	50.2	Not reported	Not reported	Not reported
Phase 1, Schedule A: 270 mg	4.48	32.1	Not reported	Not reported	Not reported
Phase 1, Schedule A: 300 mg	5.78	85.6	Not reported	Not reported	Not reported
Phase 1, Schedule A: 360 mg	4.92	66.0	Not reported	Not reported	Not reported

RA, AUC0-24: Day 28

Analysis denominator · Participants

Group	Source count
Phase 1, Schedule A: 20 mg	0
Phase 1, Schedule A: 40 mg	0
Phase 1, Schedule A: 80 mg	0
Phase 1, Schedule A: 120 mg	0
Phase 1, Schedule A: 180 mg	0
Phase 1, Schedule A: 270 mg	0
Phase 1, Schedule A: 300 mg	0
Phase 1, Schedule A: 360 mg	0
Phase 1, Schedule B: 120 mg	4
Phase 1, Schedule B: 180 mg	6
Phase 1, Schedule B: 250 mg	4
Phase 2, Schedule B:360+150 mg	15

Values in Ratio · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Phase 1, Schedule B: 120 mg	6.14	33.9	Not reported	Not reported	Not reported
Phase 1, Schedule B: 180 mg	5.81	42.9	Not reported	Not reported	Not reported
Phase 1, Schedule B: 250 mg	3.40	36.9	Not reported	Not reported	Not reported
Phase 2, Schedule B:360+150 mg	9.33	85.5	Not reported	Not reported	Not reported

RA, Cmax: Day 21

Analysis denominator · Participants

Group	Source count
Phase 1, Schedule A: 20 mg	3
Phase 1, Schedule A: 40 mg	3
Phase 1, Schedule A: 80 mg	3
Phase 1, Schedule A: 120 mg	3
Phase 1, Schedule A: 180 mg	3
Phase 1, Schedule A: 270 mg	4
Phase 1, Schedule A: 300 mg	10
Phase 1, Schedule A: 360 mg	3
Phase 1, Schedule B: 120 mg	0
Phase 1, Schedule B: 180 mg	0
Phase 1, Schedule B: 250 mg	0
Phase 2, Schedule B:360+150 mg	0

Values in Ratio · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Phase 1, Schedule A: 20 mg	8.26	49.1	Not reported	Not reported	Not reported
Phase 1, Schedule A: 40 mg	3.08	33.7	Not reported	Not reported	Not reported
Phase 1, Schedule A: 80 mg	3.74	42.5	Not reported	Not reported	Not reported
Phase 1, Schedule A: 120 mg	3.54	38.4	Not reported	Not reported	Not reported
Phase 1, Schedule A: 180 mg	2.86	69.4	Not reported	Not reported	Not reported
Phase 1, Schedule A: 270 mg	3.07	59.3	Not reported	Not reported	Not reported
Phase 1, Schedule A: 300 mg	2.73	52.5	Not reported	Not reported	Not reported
Phase 1, Schedule A: 360 mg	4.06	69.0	Not reported	Not reported	Not reported

RA, Cmax: Day 28

Analysis denominator · Participants

Group	Source count
Phase 1, Schedule A: 20 mg	0
Phase 1, Schedule A: 40 mg	0
Phase 1, Schedule A: 80 mg	0
Phase 1, Schedule A: 120 mg	0
Phase 1, Schedule A: 180 mg	0
Phase 1, Schedule A: 270 mg	0
Phase 1, Schedule A: 300 mg	0
Phase 1, Schedule A: 360 mg	0
Phase 1, Schedule B: 120 mg	4
Phase 1, Schedule B: 180 mg	6
Phase 1, Schedule B: 250 mg	4
Phase 2, Schedule B:360+150 mg	15

Values in Ratio · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Phase 1, Schedule B: 120 mg	6.19	44.4	Not reported	Not reported	Not reported
Phase 1, Schedule B: 180 mg	3.75	55.3	Not reported	Not reported	Not reported
Phase 1, Schedule B: 250 mg	2.59	29.6	Not reported	Not reported	Not reported
Phase 2, Schedule B:360+150 mg	2.13	70.7	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG000
spread
46.9
value
8.99
group Id
OG001
spread
26.0
value
3.72
group Id
OG002
spread
18.3
value
4.42
group Id
OG003
spread
9.88
value
3.91
group Id
OG004
spread
50.2
value
4.14
group Id
OG005
spread
32.1
value
4.48
group Id
OG006
spread
85.6
value
5.78
group Id
OG007
spread
66.0
value
4.92
denoms
counts
group Id
OG000
value
3
group Id
OG001
value
3
group Id
OG002
value
3
group Id
OG003
value
3
group Id
OG004
value
3
group Id
OG005
value
4
group Id
OG006
value
10
group Id
OG007
value
3
group Id
OG008
value
0
group Id
OG009
value
0
group Id
OG010
value
0
group Id
OG011
value
0
units
Participants
title
RA, AUC0-24: Day 21
categories
measurements
group Id
OG008
spread
33.9
value
6.14
group Id
OG009
spread
42.9
value
5.81
group Id
OG010
spread
36.9
value
3.40
group Id
OG011
spread
85.5
value
9.33
denoms
counts
group Id
OG000
value
0
group Id
OG001
value
0
group Id
OG002
value
0
group Id
OG003
value
0
group Id
OG004
value
0
group Id
OG005
value
0
group Id
OG006
value
0
group Id
OG007
value
0
group Id
OG008
value
4
group Id
OG009
value
6
group Id
OG010
value
4
group Id
OG011
value
15
units
Participants
title
RA, AUC0-24: Day 28
categories
measurements
group Id
OG000
spread
49.1
value
8.26
group Id
OG001
spread
33.7
value
3.08
group Id
OG002
spread
42.5
value
3.74
group Id
OG003
spread
38.4
value
3.54
group Id
OG004
spread
69.4
value
2.86
group Id
OG005
spread
59.3
value
3.07
group Id
OG006
spread
52.5
value
2.73
group Id
OG007
spread
69.0
value
4.06
denoms
counts
group Id
OG000
value
3
group Id
OG001
value
3
group Id
OG002
value
3
group Id
OG003
value
3
group Id
OG004
value
3
group Id
OG005
value
4
group Id
OG006
value
10
group Id
OG007
value
3
group Id
OG008
value
0
group Id
OG009
value
0
group Id
OG010
value
0
group Id
OG011
value
0
units
Participants
title
RA, Cmax: Day 21
categories
measurements
group Id
OG008
spread
44.4
value
6.19
group Id
OG009
spread
55.3
value
3.75
group Id
OG010
spread
29.6
value
2.59
group Id
OG011
spread
70.7
value
2.13
denoms
counts
group Id
OG000
value
0
group Id
OG001
value
0
group Id
OG002
value
0
group Id
OG003
value
0
group Id
OG004
value
0
group Id
OG005
value
0
group Id
OG006
value
0
group Id
OG007
value
0
group Id
OG008
value
4
group Id
OG009
value
6
group Id
OG010
value
4
group Id
OG011
value
15
units
Participants
title
RA, Cmax: Day 28

denoms

counts
group Id
OG000
value
3
group Id
OG001
value
3
group Id
OG002
value
3
group Id
OG003
value
3
group Id
OG004
value
3
group Id
OG005
value
4
group Id
OG006
value
10
group Id
OG007
value
3
group Id
OG008
value
4
group Id
OG009
value
6
group Id
OG010
value
4
group Id
OG011
value
15
units
Participants

description

Plasma samples were collected and used for pharmacokinetics assessments. Mean values of PK parameters are presented with the coefficient of variation (CV%).

dispersion Type

Standard Deviation

groups

description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
id
OG000
title
Phase 1, Schedule A: 20 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 40 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG001
title
Phase 1, Schedule A: 40 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 80 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG002
title
Phase 1, Schedule A: 80 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG003
title
Phase 1, Schedule A: 120 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG004
title
Phase 1, Schedule A: 180 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 270 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG005
title
Phase 1, Schedule A: 270 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 300 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG006
title
Phase 1, Schedule A: 300 mg
description
All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 360 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
id
OG007
title
Phase 1, Schedule A: 360 mg
description
All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.
id
OG008
title
Phase 1, Schedule B: 120 mg
description
All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.
id
OG009
title
Phase 1, Schedule B: 180 mg
description
All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 250 mg administered orally once daily for 28 consecutive days, in a 28-day cycle
id
OG010
title
Phase 1, Schedule B: 250 mg
description
Participants who had failed standard of care including Venetoclax and Gilteritining based therapies. NMS-03592088 was administered, on Cycle 1, at 360 mg/day (loading dose) for 5 consecutive days, followed by 150 mg/day (maintenance dose) for 23 consecutive days. The same maintenance dose (150 mg/day) was administered from Cycle 2 onwards
id
OG011
title
Phase 2, Schedule B:360+150 mg

param Type

MEAN

population Description

Participants evaluable for PK analysis (treated participants were considered evaluable if they had sufficient baseline and on-study sampled material to provide interpretable results). The plasma PK of NMS-03592088 and 2 metabolites NMS-03593860 and NMS-03603422 were collected, and PK profile characterised. Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.

reporting Status

POSTED

time Frame

Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.

title

Pharmacokinetic Parameters: Accumulation Ratios (RA) for AUC0-24 and Cmax

type

SECONDARY

unit Of Measure

Ratio

Download exact source JSON → · Snapshot ctgov-results-25a395029948b04d52b1253f

Preserved source evidence · Not medical advice