NCT00585195 · OUTCOME

Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

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

Measure: GEOMETRIC_MEAN
Unit: nanogram 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

Cmax is defined as the observed maximum plasma concentration post drug administration.

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 per milliliter · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)	14.98	19	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam	19.26	38	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)	13.65	10	Not reported	Not reported	Not reported
Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam	32.62	40	Not reported	Not reported	Not reported
RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)	12.78	41	Not reported	Not reported	Not reported
RP2D Cohort: Crizotinib 250 mg + Midazolam	25.37	67	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
96.59
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
179.63
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
131.72
ci Lower Limit
172.14
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
331.93
group Ids
OG002
OG003
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
239.03
ci Lower Limit
139.33
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
291.58
group Ids
OG004
OG005
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
201.56

Complete source fields

analyses

ci Lower Limit
96.59
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
179.63
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
131.72
ci Lower Limit
172.14
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
331.93
group Ids
OG002
OG003
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
239.03
ci Lower Limit
139.33
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
291.58
group Ids
OG004
OG005
non Inferiority Type
SUPERIORITY
param Type
Ratio of adjusted geometric means
param Value
201.56

classes

categories
measurements
group Id
OG000
spread
19
value
14.98
group Id
OG001
spread
38
value
19.26
group Id
OG002
spread
10
value
13.65
group Id
OG003
spread
40
value
32.62
group Id
OG004
spread
41
value
12.78
group Id
OG005
spread
67
value
25.37

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

Cmax is defined as the observed maximum plasma concentration post drug administration.

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

Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

type

PRIMARY

unit Of Measure

nanogram per milliliter

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Preserved source evidence · Not medical advice