NCT00652626 · OUTCOME

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine

Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function · Source last updated 2019-11-19

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

Measure: GEOMETRIC_MEAN
Unit: ng*hr/mL
Interval / dispersion: Geometric Coefficient of Variation
Time frame: Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

What was measured

The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine, after a single dose (Day 1) and multiple doses (Day 5), calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation: AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.

Analysis population: Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.

Groups in this outcome

Normal RF: Azacitidine 75 mg/m^2

Participants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5.

Severe RI: Azacitidine 75 mg/m^2

Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5.

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
Normal RF: Azacitidine 75 mg/m^2	6
Severe RI: Azacitidine 75 mg/m^2	6

Reported measurements

Day 1

Values in ng*hr/mL · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Normal RF: Azacitidine 75 mg/m^2	946.22	39.05	Not reported	Not reported	Not reported
Severe RI: Azacitidine 75 mg/m^2	1573.82	63.46	Not reported	Not reported	Not reported

Day 5

Values in ng*hr/mL · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Normal RF: Azacitidine 75 mg/m^2	857.64	9.94	Not reported	Not reported	Not reported
Severe RI: Azacitidine 75 mg/m^2	1210.92	49.07	Not reported	Not reported	Not reported

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

ci Lower Limit
108.6
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
254.6
estimate Comment
Ratio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
group Description
Comparison of AUC0-inf after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER_LEGACY
param Type
Ratio (%) of Geometric Means
param Value
166.3
ci Lower Limit
92.2
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
216.2
estimate Comment
Ratio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
group Description
Comparison of AUC0-inf after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER_LEGACY
param Type
Ratio (%) of Geometric Means
param Value
141.2

Complete source fields

analyses

ci Lower Limit
108.6
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
254.6
estimate Comment
Ratio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
group Description
Comparison of AUC0-inf after a single dose (Day 1) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER_LEGACY
param Type
Ratio (%) of Geometric Means
param Value
166.3
ci Lower Limit
92.2
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
216.2
estimate Comment
Ratio of geometric mean is calculated as Severe RI/Normal RF and expressed as a percentage.
group Description
Comparison of AUC0-inf after multiple doses (Day 5) in participants with normal renal function and participants with severe renal impairment. Geometric means, ratio and 90% CI of ratio of geometric means are from an analysis of variance model with renal function group (normal and severe), visit (Day 1 and Day 5), renal function group by visit interaction as fixed effect, and patient nested within renal function group as a random effect on the nature log-transformed pharmacokinetic parameters.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER_LEGACY
param Type
Ratio (%) of Geometric Means
param Value
141.2

classes

categories
measurements
group Id
OG000
spread
39.05
value
946.22
group Id
OG001
spread
63.46
value
1573.82
title
Day 1
categories
measurements
group Id
OG000
spread
9.94
value
857.64
group Id
OG001
spread
49.07
value
1210.92
title
Day 5

denoms

counts
group Id
OG000
value
6
group Id
OG001
value
6
units
Participants

description

dispersion Type

Geometric Coefficient of Variation

groups

description
Participants with normal renal function (RF) received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5.
id
OG000
title
Normal RF: Azacitidine 75 mg/m^2
description
Participants with severe renal impairment (RI) received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5.
id
OG001
title
Severe RI: Azacitidine 75 mg/m^2

param Type

GEOMETRIC_MEAN

population Description

Pharmacokinetic Population, consisting of all participants with evaluable plasma or urine concentration data for azacitidine. This analysis was performed for participants in the 2 treatment groups who received azacitidine treatment for 5 days.

reporting Status

POSTED

time Frame

Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose

title

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine

type

PRIMARY

unit Of Measure

ng*hr/mL

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Preserved source evidence · Not medical advice