Study of the Pharmacokinetics and Safety of Carfilzomib i... | NCT01949532

ID	Type	Description	Link
20130401	Other Identifier	Sponsor

Label	Type	Description	Intervention Names
Normal Renal Function	Experimental	Participants with normal renal function (creatinine clearance [CrCl] ≥ 75 mL/min) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.	Drug: Carfilzomib
End Stage Renal Disease	Experimental	Participants with end-stage renal disease (on hemodialysis) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.	Drug: Carfilzomib

Name	Type	Description	Arm Group Labels	Other Names
Carfilzomib	Drug	Carfilzomib was administered by IV injection.	End Stage Renal Disease Normal Renal Function

Measure	Description	Time Frame
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2	Carfilzomib plasma concentrations for pharmacokinetic (PK) analyses were measured by liquid chromatography with tandem mass spectrometry. The lower limit of quantitation (LLOQ) for the assay was 0.3 ng/mL.	Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Karmanos Cancer Institute		Detroit	Michigan		United States
North Shore-LIJ Health System/Center for Advanced Medicine - North Shore University Hospital

ID	Title	Description
FG000	Normal Renal Function	Participants with normal renal function (creatinine clearance [CrCl] ≥ 75 mL/min) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

Carfilzomib plasma concentrations for pharmacokinetic (PK) analyses were measured by liquid chromatography with tandem mass spectrometry. The lower limit of quantitation (LLOQ) for the assay was 0.3 ng/mL.

PK evaluable population for cycle 2, day 1. The PK evaluable population is defined as participants with sufficient carfilzomib plasma concentration versus time data for the estimation of PK parameters by non-compartmental analysis on cycle 1, day 16 and/or cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants	OG00010 OG0018

Title

Denominators

Categories

Title	Measurements
	OG000563± 41.9 OG001747± 143.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio of geometric means	132.75			2-Sided	90	70.60	249.63			The point estimates of the geometric mean ratios for the PK parameters were calculated by exponentiation of the differences in the least-squares means between the renal impairment group (test) and participants with normal renal function (reference).		Superiority or Other

Primary

Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units

Secondary

Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants

Secondary

Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters/hour

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2

PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters

Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants for whom the coefficient of correlation (R²) was < 0.8 were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants with a coefficient of correlation (R²) < 0.8 were excluded.

Posted

Median

Full Range

hours

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units

Secondary

Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters/hour

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1

PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

liters

Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14

PK evaluable population; One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. "n" indicates the number of participants included in the analyses at each time point.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14

PK evaluable population. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded. AUC0-∞ could not be calculated for the ESRD group as the extrapolated portion (AUCextr) was greater than 20% in all participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Maximum Observed Plasma Concentration for Metabolite PR-389/M14

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants

Secondary

Terminal Half-life (T½) of Metabolite PR-389/M14

PK evaluable population. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded. T½ could not be calculated for the ESRD group as the extrapolated portion (AUCextr) was greater than 20% in all participants.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15

PK evaluable population. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Secondary

Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants

Secondary

Terminal Half-life (T½) of Metabolite PR-413/M15

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts

Secondary

Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants

Secondary

Terminal Half-life (T½) of Metabolite PR-519/M16

PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs)

Determination of the severity of all adverse events was assessed following the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Fatal.

A Serious AE is an AE that meets one or more of the following criteria:

Death,
Life-threatening experience;
Requires in-patient hospitalization or prolongation of an existing hospitalization,
Results in persistent or significant disability/incapacity,
Is a congenital anomaly/birth defect,
Important medical events that may not result in death, be life-threatening, or require hospitalization.

Treatment-related adverse events (TRAEs) are adverse events considered related to carfilzomib by the investigator, including those with unknown relationship.

All treated participants

Posted

Number

participants

From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.

ID	Title	Description
OG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
OG001

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Microangiopathic haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0012 affected11 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected11 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0012 affected11 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Urosepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Procedural hypotension	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Troponin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Delirium	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Acute interstitial pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Haematoma	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected15 at risk EG0015 affected11 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected15 at risk EG0011 affected11 at risk
Angina pectoris	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Cardiovascular disorder	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Ear congestion	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Meniere's disease	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Cataract	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Exophthalmos	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Eye discharge	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Eye inflammation	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Eye pruritus	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Eye swelling	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Eyelid oedema	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Lacrimation increased	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Ocular discomfort	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Photophobia	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Vision blurred	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Visual acuity reduced	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0014 affected11 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected15 at risk EG0015 affected11 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Flatulence	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Mouth swelling	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected15 at risk EG0016 affected11 at risk
Retching	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Tooth disorder	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0014 affected11 at risk
Application site reaction	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Catheter site inflammation	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0011 affected11 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected15 at risk EG0015 affected11 at risk
General physical health deterioration	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Influenza like illness	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Infusion site erythema	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Infusion site pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Injury associated with device	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Oedema	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected15 at risk EG0012 affected11 at risk
Sluggishness	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Candida infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Catheter site infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Conjunctivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Ear infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected11 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Blood calcium decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Blood calcium increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Blood uric acid increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Carbon dioxide decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Eosinophil count increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Haemoglobin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Lymphocyte count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Monocyte count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Monocyte count increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Neutrophil count increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Olfactory test abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Protein total decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Red blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Troponin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0013 affected11 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Diastasis recti abdominis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected11 at risk
Soft tissue mass	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Gastrointestinal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Areflexia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Dysgeusia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected15 at risk EG0013 affected11 at risk
Lethargy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Migraine	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Sciatica	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Somnolence	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Confusional state	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected11 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected11 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0011 affected11 at risk
Mood altered	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Dysuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Renal failure	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected15 at risk EG0013 affected11 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected15 at risk EG0011 affected11 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Dyspnoea paroxysmal nocturnal	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected15 at risk EG0011 affected11 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Oropharyngeal plaque	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected11 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected11 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected11 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Flushing	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected11 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected15 at risk EG0011 affected11 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected15 at risk EG0012 affected11 at risk
Peripheral coldness	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk
Venous thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected11 at risk

ID	Term
D009101	Multiple Myeloma
D007676	Kidney Failure, Chronic

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
BG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Normal Renal Function	Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.			10	15	14	15
EG001	End Stage Renal Disease	Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.			9	11	10	11