NCT01393964 · OUTCOME

Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method

Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function · Source last updated 2017-08-03

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

Measure: GEOMETRIC_MEAN
Unit: µg*h/mL
Interval / dispersion: Geometric Coefficient of Variation
Time frame: Day 1 of Cycle 1 to 28 days post dose

What was measured

The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg\*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value \< 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group

Analysis population: The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

Groups in this outcome

Elotuzumab + LD in Normal Renal Function (NRF) Participants

LD=Combination of lenalidomide and dexamethasone. Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).

Elotuzumab + LD in Severe Renal Impairment (SRI) Participants

Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl \< 30 ml/min but no dialysis.

Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants

Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.

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
Elotuzumab + LD in Normal Renal Function (NRF) Participants	8
Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	7
Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants	8

Reported measurements

AUC (0-T)

Values in µg*h/mL · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Elotuzumab + LD in Normal Renal Function (NRF) Participants	39559	28	Not reported	Not reported	Not reported
Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	50080	20	Not reported	Not reported	Not reported
Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants	45937	31	Not reported	Not reported	Not reported

AUC (INF)

Values in µg*h/mL · Interval/dispersion: Geometric Coefficient of Variation
Group	Value	Spread	Lower	Upper	Comment
Elotuzumab + LD in Normal Renal Function (NRF) Participants	46401	39	Not reported	Not reported	Not reported
Elotuzumab + LD in Severe Renal Impairment (SRI) Participants	60255	31	Not reported	Not reported	Not reported
Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants	51227	39	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
95.52
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
167.783
group Description
AUC(0-T). The reference arm is NRF participants.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.164
param Type
Ratio of Adjusted Means
param Value
126.596
statistical Method
ANOVA
ci Lower Limit
88.458
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
152.439
group Description
AUC(0-T). The reference arm is NRF participants.
group Ids
OG000
OG002
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.355
param Type
Ratio of Adjusted Means
param Value
116.123
statistical Method
ANOVA
ci Lower Limit
90.366
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
186.609
group Description
AUC (INF). The reference arm is NRF participants.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.228
param Type
Ratio of Adjusted Means
param Value
129.858
statistical Method
ANOVA
ci Lower Limit
76.825
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
158.647
group Description
AUC(INF). The reference arm is NRF participants.
group Ids
OG000
OG002
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.642
param Type
Ratio of Adjusted Means
param Value
110.400
statistical Method
ANOVA

Complete source fields

analyses

ci Lower Limit
95.52
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
167.783
group Description
AUC(0-T). The reference arm is NRF participants.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.164
param Type
Ratio of Adjusted Means
param Value
126.596
statistical Method
ANOVA
ci Lower Limit
88.458
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
152.439
group Description
AUC(0-T). The reference arm is NRF participants.
group Ids
OG000
OG002
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.355
param Type
Ratio of Adjusted Means
param Value
116.123
statistical Method
ANOVA
ci Lower Limit
90.366
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
186.609
group Description
AUC (INF). The reference arm is NRF participants.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.228
param Type
Ratio of Adjusted Means
param Value
129.858
statistical Method
ANOVA
ci Lower Limit
76.825
ci Num Sides
TWO_SIDED
ci Pct Value
90
ci Upper Limit
158.647
group Description
AUC(INF). The reference arm is NRF participants.
group Ids
OG000
OG002
non Inferiority Type
SUPERIORITY_OR_OTHER
p Value
0.642
param Type
Ratio of Adjusted Means
param Value
110.400
statistical Method
ANOVA

classes

categories
measurements
group Id
OG000
spread
28
value
39559
group Id
OG001
spread
20
value
50080
group Id
OG002
spread
31
value
45937
title
AUC (0-T)
categories
measurements
group Id
OG000
spread
39
value
46401
group Id
OG001
spread
31
value
60255
group Id
OG002
spread
39
value
51227
title
AUC (INF)

denoms

counts
group Id
OG000
value
8
group Id
OG001
value
7
group Id
OG002
value
8
units
Participants

description

dispersion Type

Geometric Coefficient of Variation

groups

description
LD=Combination of lenalidomide and dexamethasone. Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and every 2 weeks (Q2W) beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on creatinine clearance (CrCl) calculated using the Cockcroft-Gault (C-G) formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg oral dose (po) on weeks without elotuzumab; and as a split dose of 28 mg po 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G Creatinine Clearance CrCl Method was used to determine renal function. NRF =CrCl ≥ 90 milliliters per minute (mL/min).
id
OG000
title
Elotuzumab + LD in Normal Renal Function (NRF) Participants
description
Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg IV was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, and Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly PO as 40mg dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. SRI= estimated CrCl \< 30 ml/min but no dialysis.
id
OG001
title
Elotuzumab + LD in Severe Renal Impairment (SRI) Participants
description
Treatment was administered in 28 day cycles: Elotuzumab 10 mg/kg intravenous (IV) was administered on Day 1 only for Cycle 1, weekly for Cycles 2 and 3, Q2W beginning with Cycle 4 and thereafter. Lenalidomide dosing was based on CrCl calculated using the C-G formula based on Day 1 creatinine and Day 1 weight measured at each cycle. Dexamethasone was administered weekly as a 40mg PO dose on weeks without elotuzumab; and as a split dose of 28 mg PO 3 to 24 hours before and 8 mg IV at least 45 minutes before the start of the elotuzumab infusion on weeks with elotuzumab. C-G CrCl Method was used to determine renal function. ESRD= requires hemodialysis.
id
OG002
title
Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants

param Type

GEOMETRIC_MEAN

population Description

The analyses of primary endpoint of PK parameters were conducted by renal functions as determined by CrCl C-G method in those participants who were treated with at least one dose of study drug and had evaluable pre- and post-treatment values.

reporting Status

POSTED

time Frame

Day 1 of Cycle 1 to 28 days post dose

title

Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method

type

PRIMARY

unit Of Measure

µg*h/mL

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Preserved source evidence · Not medical advice