NCT00866281 · OUTCOME

Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221

A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia · Source last updated 2015-12-22

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

Measure: MEAN
Unit: nanograms/milliliters (ng/mL)
Interval / dispersion: Standard Deviation
Time frame: Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3)

What was measured

The plasma concentrations of midostaurin (PKC412) and its two major metabolites, CGP62221 and CGP52421 were determined by using a validated liquid chromatography/tandem mass spectrometry method.

Analysis population: The analysis was performed in pharmacokinetic (PK) set population defined as all safety set participants who had at least one valid (measurable) PK sample of midostaurin, and who had no significant restricted co-medications.

Groups in this outcome

Cohort 1: Midostaurin (30 Milligrams/Meters^2)

Participants received bodyweight and body surface area (BSA) stratified dose of midostaurin 30 mg/m\^2 bid through oral route. The total daily dose in 30 mg/m\^2 bid cohort was 60 mg/m\^2.

Cohort 2: Midostaurin (60 mg/m^2)

Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m\^2 bid through oral route. The total daily dose in 60 mg/m\^2 bid cohort was 120 mg/m\^2.

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
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	7
Cohort 2: Midostaurin (60 mg/m^2)	15

Reported measurements

PKC412-Cycle 1/Day 1 (1 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1678	652.817	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2330.88	1290.136	Not reported	Not reported	Not reported

PKC412-Cycle 1/Day 1 (2 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1762.5	226.771	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2449.09	936.039	Not reported	Not reported	Not reported

PKC412-Cycle 1/Day 1 (3 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1891.67	505.941	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2287.5	1421.365	Not reported	Not reported	Not reported

PKC412-Cycle 1/Day 1 (12 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	939.17	347.925	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2068.85	2183.946	Not reported	Not reported	Not reported

PKC412-Cycle 1/Day 5 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	2444	936.659	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2610.1	2480.716	Not reported	Not reported	Not reported

PKC412-Cycle 1/Day 7 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1945	643.467	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2028	2071.949	Not reported	Not reported	Not reported

PKC412-Cycle 2/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1832.5	773.881	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	726	379.953	Not reported	Not reported	Not reported

PKC412-Cycle 3/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	962	505.146	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	674	340.776	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 1 (1 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	106.18	89.473	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	228.33	148.469	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 1 (2 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	208.95	183.22	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	458.75	281.882	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 1 (3 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	333.4	227.863	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	563.63	276.938	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 1 (12 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	424.35	299.416	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	730.31	385.698	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 5 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	3182	1756.778	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	3360.3	2002.498	Not reported	Not reported	Not reported

CGP62221-Cycle 1/Day 7 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	3390	1400.071	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2895	1893.347	Not reported	Not reported	Not reported

CGP62221-Cycle 2/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	2380	728.331	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	1614.14	1057.585	Not reported	Not reported	Not reported

CGP62221-Cycle 3/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1140.67	189.16	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	1759.2	923.668	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 1 (1 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	71.64	42.325	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	111.58	78.187	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 1 (2 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	113.23	54.831	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	189.65	128.879	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 1 (3 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	152.18	78.405	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	236.19	144.723	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 1 (12 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	139.27	68.198	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	259.52	148.943	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 5 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1018	259.014	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	1581	509.208	Not reported	Not reported	Not reported

CGP52421-Cycle 1/Day 7 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	1269	453.963	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2129	341.97	Not reported	Not reported	Not reported

CGP52421-Cycle 2/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	2350	1110.465	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	2640	541.018	Not reported	Not reported	Not reported

CGP52421-Cycle 3/Day 1 (0 hour)

Values in nanograms/milliliters (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Cohort 1: Midostaurin (30 Milligrams/Meters^2)	2386.67	277.909	Not reported	Not reported	Not reported
Cohort 2: Midostaurin (60 mg/m^2)	3488	1511.529	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG000
spread
652.817
value
1678
group Id
OG001
spread
1290.136
value
2330.88
title
PKC412-Cycle 1/Day 1 (1 hour)
categories
measurements
group Id
OG000
spread
226.771
value
1762.5
group Id
OG001
spread
936.039
value
2449.09
title
PKC412-Cycle 1/Day 1 (2 hour)
categories
measurements
group Id
OG000
spread
505.941
value
1891.67
group Id
OG001
spread
1421.365
value
2287.5
title
PKC412-Cycle 1/Day 1 (3 hour)
categories
measurements
group Id
OG000
spread
347.925
value
939.17
group Id
OG001
spread
2183.946
value
2068.85
title
PKC412-Cycle 1/Day 1 (12 hour)
categories
measurements
group Id
OG000
spread
936.659
value
2444
group Id
OG001
spread
2480.716
value
2610.1
title
PKC412-Cycle 1/Day 5 (0 hour)
categories
measurements
group Id
OG000
spread
643.467
value
1945
group Id
OG001
spread
2071.949
value
2028
title
PKC412-Cycle 1/Day 7 (0 hour)
categories
measurements
group Id
OG000
spread
773.881
value
1832.5
group Id
OG001
spread
379.953
value
726
title
PKC412-Cycle 2/Day 1 (0 hour)
categories
measurements
group Id
OG000
spread
505.146
value
962
group Id
OG001
spread
340.776
value
674
title
PKC412-Cycle 3/Day 1 (0 hour)
categories
measurements
group Id
OG000
spread
89.473
value
106.18
group Id
OG001
spread
148.469
value
228.33
title
CGP62221-Cycle 1/Day 1 (1 hour)
categories
measurements
group Id
OG000
spread
183.22
value
208.95
group Id
OG001
spread
281.882
value
458.75
title
CGP62221-Cycle 1/Day 1 (2 hour)
categories
measurements
group Id
OG000
spread
227.863
value
333.4
group Id
OG001
spread
276.938
value
563.63
title
CGP62221-Cycle 1/Day 1 (3 hour)
categories
measurements
group Id
OG000
spread
299.416
value
424.35
group Id
OG001
spread
385.698
value
730.31
title
CGP62221-Cycle 1/Day 1 (12 hour)

denoms

counts
group Id
OG000
value
7
group Id
OG001
value
15
units
Participants

description

The plasma concentrations of midostaurin (PKC412) and its two major metabolites, CGP62221 and CGP52421 were determined by using a validated liquid chromatography/tandem mass spectrometry method.

dispersion Type

Standard Deviation

groups

description
Participants received bodyweight and body surface area (BSA) stratified dose of midostaurin 30 mg/m\^2 bid through oral route. The total daily dose in 30 mg/m\^2 bid cohort was 60 mg/m\^2.
id
OG000
title
Cohort 1: Midostaurin (30 Milligrams/Meters^2)
description
Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m\^2 bid through oral route. The total daily dose in 60 mg/m\^2 bid cohort was 120 mg/m\^2.
id
OG001
title
Cohort 2: Midostaurin (60 mg/m^2)

param Type

MEAN

population Description

The analysis was performed in pharmacokinetic (PK) set population defined as all safety set participants who had at least one valid (measurable) PK sample of midostaurin, and who had no significant restricted co-medications.

reporting Status

POSTED

time Frame

Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3)

title

Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221

type

SECONDARY

unit Of Measure

nanograms/milliliters (ng/mL)

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Preserved source evidence · Not medical advice