NCT01943851 · OUTCOME

Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite)

A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies · Source last updated 2024-10-01

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

Measure: GEOMETRIC_MEAN
Unit: Ratio
Interval / dispersion: Geometric Coefficient of Variation
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

What was measured

Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.

Analysis population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.

Groups in this outcome

Part 1: GSK525762 5 mg QD

Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.

Part 1: GSK525762 10 mg QD

Participants were administered once daily oral dose of 10 mg GSK525762.

Part 1: GSK525762 20 mg QD

Participants were administered once daily oral dose of 20 mg GSK525762.

Part 1: GSK525762 30 mg QD MM

Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.

Part 1: GSK525762 40 mg QD

Participants were administered once daily oral dose of 40 mg GSK525762.

Part 1: GSK525762 40 mg QD MM

Participants with multiple myeloma were administered once daily oral dose of 40 mg GSK525762.

Part 1: GSK525762 60 mg QD AML

Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.

Part 1: GSK525762 60 mg QD NHL

Participants with Non-Hodgkin's Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.

Part 1: GSK525762 60 mg QD MM

Participants with MM were administered once daily oral dose of 60 mg GSK525762.

Part 1: GSK525762 75 mg QD AML

Participants with AML were administered once daily oral dose of 75 mg GSK525762.

Part 1: GSK525762 80 mg QD

Participants were administered once daily oral dose of 80 mg GSK525762.

Part 1: GSK525762 80 mg QD AML

Participants with AML were administered once daily oral dose of 80 mg GSK525762.

Part 1: GSK525762 80 mg QD NHL

Participants with NHL were administered once daily oral dose of 80 mg GSK525762.

Part 1: GSK525762 100 mg QD AML

Participants with AML were administered once daily oral dose of 100 mg GSK525762.

Part 1: GSK525762 120 mg QD AML

Participants with AML were administered once daily oral dose of 120 mg GSK525762.

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
Part 1: GSK525762 5 mg QD	0
Part 1: GSK525762 10 mg QD	0
Part 1: GSK525762 20 mg QD	0
Part 1: GSK525762 30 mg QD MM	4
Part 1: GSK525762 40 mg QD	0
Part 1: GSK525762 40 mg QD MM	1
Part 1: GSK525762 60 mg QD AML	0
Part 1: GSK525762 60 mg QD NHL	8
Part 1: GSK525762 60 mg QD MM	1
Part 1: GSK525762 75 mg QD AML	6
Part 1: GSK525762 80 mg QD	0
Part 1: GSK525762 80 mg QD AML	0
Part 1: GSK525762 80 mg QD NHL	4
Part 1: GSK525762 100 mg QD AML	6
Part 1: GSK525762 120 mg QD AML	0

Reported measurements

Source class 1

Values in Ratio · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Part 1: GSK525762 30 mg QD MM	0.92	25.58	Not reported	Not reported	Not reported
Part 1: GSK525762 40 mg QD MM	0.96	NA	Not reported	Not reported	Geometric coefficient of variation could not be calculated for a single participant
Part 1: GSK525762 60 mg QD NHL	1.18	32.33	Not reported	Not reported	Not reported
Part 1: GSK525762 60 mg QD MM	0.63	NA	Not reported	Not reported	Geometric coefficient of variation could not be calculated for a single participant
Part 1: GSK525762 75 mg QD AML	1.20	13.74	Not reported	Not reported	Not reported
Part 1: GSK525762 80 mg QD NHL	1.06	9.48	Not reported	Not reported	Not reported
Part 1: GSK525762 100 mg QD AML	1.87	57.15	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG003
spread
25.58
value
0.92
comment
Geometric coefficient of variation could not be calculated for a single participant
group Id
OG005
spread
NA
value
0.96
group Id
OG007
spread
32.33
value
1.18
comment
Geometric coefficient of variation could not be calculated for a single participant
group Id
OG008
spread
NA
value
0.63
group Id
OG009
spread
13.74
value
1.20
group Id
OG012
spread
9.48
value
1.06
group Id
OG013
spread
57.15
value
1.87

denoms

counts
group Id
OG000
value
0
group Id
OG001
value
0
group Id
OG002
value
0
group Id
OG003
value
4
group Id
OG004
value
0
group Id
OG005
value
1
group Id
OG006
value
0
group Id
OG007
value
8
group Id
OG008
value
1
group Id
OG009
value
6
group Id
OG010
value
0
group Id
OG011
value
0
units
Participants

description

dispersion Type

Geometric Coefficient of Variation

groups

description
Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762.
id
OG000
title
Part 1: GSK525762 5 mg QD
description
Participants were administered once daily oral dose of 10 mg GSK525762.
id
OG001
title
Part 1: GSK525762 10 mg QD
description
Participants were administered once daily oral dose of 20 mg GSK525762.
id
OG002
title
Part 1: GSK525762 20 mg QD
description
Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762.
id
OG003
title
Part 1: GSK525762 30 mg QD MM
description
Participants were administered once daily oral dose of 40 mg GSK525762.
id
OG004
title
Part 1: GSK525762 40 mg QD
description
Participants with multiple myeloma were administered once daily oral dose of 40 mg GSK525762.
id
OG005
title
Part 1: GSK525762 40 mg QD MM
description
Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762.
id
OG006
title
Part 1: GSK525762 60 mg QD AML
description
Participants with Non-Hodgkin's Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762.
id
OG007
title
Part 1: GSK525762 60 mg QD NHL
description
Participants with MM were administered once daily oral dose of 60 mg GSK525762.
id
OG008
title
Part 1: GSK525762 60 mg QD MM
description
Participants with AML were administered once daily oral dose of 75 mg GSK525762.
id
OG009
title
Part 1: GSK525762 75 mg QD AML
description
Participants were administered once daily oral dose of 80 mg GSK525762.
id
OG010
title
Part 1: GSK525762 80 mg QD
description
Participants with AML were administered once daily oral dose of 80 mg GSK525762.
id
OG011
title
Part 1: GSK525762 80 mg QD AML

param Type

GEOMETRIC_MEAN

population Description

PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.

reporting Status

POSTED

time Frame

Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose

title

Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite)

type

SECONDARY

unit Of Measure

Ratio

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

Preserved source evidence · Not medical advice