NCT00585195 · OUTCOME

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib

A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer · Source last updated 2023-02-08

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

Measure: GEOMETRIC_MEAN
Unit: nanogram*hour per milliliter
Interval / dispersion: Geometric Coefficient of Variation
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

What was measured

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Analysis population: The PK concentration population of midazolam included all participants treated with midazolam (including Day -7 dose) who have at least 1 concentration of midazolam.

Groups in this outcome

Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)

Participants who did not receive Crizotinib on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam

Participants received Crizotinib 100 mg capsule or tablet orally QD along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.

Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)

Participants who did not receive Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet BID on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam

Participants received Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet orally BID along with 2 mg oral dose of Midazolam on Cycle 2 Day 1.

RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)

Participants who did not receive Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet on Day -7, received single 2 mg oral dose of Midazolam on Day -7

RP2D Cohort: Crizotinib 250 mg +Midazolam

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) BID along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.

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
Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)	4
Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam	3
Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)	5
Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam	2
RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)	14
RP2D Cohort: Crizotinib 250 mg +Midazolam	8

Reported measurements

Source class 1

Values in nanogram*hour per milliliter · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)	41.77	27	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam	90.78	33	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)	37.71	38	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam	151.45	31	Not reported	Not reported	Not reported
RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)	32.10	36	Not reported	Not reported	Not reported
RP2D Cohort: Crizotinib 250 mg +Midazolam	112.78	87	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
161.41
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
289.56
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
216.19
ci Lower Limit
141.09
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
868.23
group Ids
OG002
OG003
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
350.00
ci Lower Limit
263.22
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
507.31
group Ids
OG004
OG005
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
365.43

Complete source fields

analyses

ci Lower Limit
161.41
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
289.56
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
216.19
ci Lower Limit
141.09
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
868.23
group Ids
OG002
OG003
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
350.00
ci Lower Limit
263.22
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
507.31
group Ids
OG004
OG005
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
365.43

classes

categories
measurements
group Id
OG000
spread
27
value
41.77
group Id
OG001
spread
33
value
90.78
group Id
OG002
spread
38
value
37.71
group Id
OG003
spread
31
value
151.45
group Id
OG004
spread
36
value
32.10
group Id
OG005
spread
87
value
112.78

denoms

counts
group Id
OG000
value
4
group Id
OG001
value
3
group Id
OG002
value
5
group Id
OG003
value
2
group Id
OG004
value
14
group Id
OG005
value
8
units
Participants

description

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

dispersion Type

Geometric Coefficient of Variation

groups

description
Participants who did not receive Crizotinib on Day -7, received single 2 mg oral dose of Midazolam on Day -7.
id
OG000
title
Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)
description
Participants received Crizotinib 100 mg capsule or tablet orally QD along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.
id
OG001
title
Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam
description
Participants who did not receive Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet BID on Day -7, received single 2 mg oral dose of Midazolam on Day -7.
id
OG002
title
Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)
description
Participants received Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet orally BID along with 2 mg oral dose of Midazolam on Cycle 2 Day 1.
id
OG003
title
Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam
description
Participants who did not receive Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet on Day -7, received single 2 mg oral dose of Midazolam on Day -7
id
OG004
title
RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)
description
Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) BID along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.
id
OG005
title
RP2D Cohort: Crizotinib 250 mg +Midazolam

param Type

GEOMETRIC_MEAN

population Description

The PK concentration population of midazolam included all participants treated with midazolam (including Day -7 dose) who have at least 1 concentration of midazolam.

reporting Status

POSTED

time Frame

pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

title

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib

type

PRIMARY

unit Of Measure

nanogram*hour per milliliter

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Preserved source evidence · Not medical advice