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Trial record 4 of 183 for:    carfilzomib OR pr-171

Study of the Safety and Pharmacokinetics of Carfilzomib in Patients With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00721734
Recruitment Status : Completed
First Posted : July 24, 2008
Results First Posted : December 9, 2015
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Multiple Myeloma
Renal Insufficiency
Intervention Drug: Carfilzomib
Enrollment 50
Recruitment Details This study enrolled patients with multiple myeloma (MM) who had relapsed or progressive disease (PD) after at least 1 (original protocol) or 2 (following protocol Amendment 1) prior therapeutic treatments or regimens. Five groups of MM patients, representing different levels of renal function, were evaluated.
Pre-assignment Details  
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Period Title: Overall Study
Started 12 12 10 8 8
Completed 4 [1] 0 [1] 2 [1] 2 [1] 2 [1]
Not Completed 8 12 8 6 6
Reason Not Completed
Progressive Disease             3             10             4             5             2
Adverse Event             3             1             4             0             3
Withdrawal by Subject             2             1             0             0             1
Other             0             0             0             1             0
[1]
Completed 12 cycles of carfilzomib treatment
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis Total
Hide Arm/Group Description

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Total of all reporting groups
Overall Number of Baseline Participants 12 12 10 8 8 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 10 participants 8 participants 8 participants 50 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  50.0%
8
  66.7%
4
  40.0%
1
  12.5%
7
  87.5%
26
  52.0%
>=65 years
6
  50.0%
4
  33.3%
6
  60.0%
7
  87.5%
1
  12.5%
24
  48.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 10 participants 8 participants 8 participants 50 participants
64.5  (5.70) 63.5  (7.85) 66.2  (9.65) 73.0  (8.23) 56.0  (7.91) 64.6  (9.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 10 participants 8 participants 8 participants 50 participants
Female
4
  33.3%
8
  66.7%
3
  30.0%
3
  37.5%
4
  50.0%
22
  44.0%
Male
8
  66.7%
4
  33.3%
7
  70.0%
5
  62.5%
4
  50.0%
28
  56.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 10 participants 8 participants 8 participants 50 participants
African American 2 2 4 1 2 11
Asian/Pacific Islander 0 2 0 0 1 3
Caucasian 10 8 6 7 5 36
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 10 participants 8 participants 8 participants 50 participants
0 (Fully active) 4 2 0 2 0 8
1 (Restrictive but ambulatory) 8 9 9 1 5 32
2 (Ambulatory but unable to work) 0 1 1 5 3 10
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.
1.Primary Outcome
Title Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
Hide Description Plasma concentrations of carfilzomib was determined by a validated liquid chromatography tandem mass spectrometry (LC MS/MS) method. The lower limit of quantitation (LLOQ) was 0.300 ng/mL. Concentration values that were below the LLOQ (BLQ) were set to zero. Pharmacokinetic (PK) parameters were calculated from the individual plasma concentrations of carfilzomib using a noncompartmental method.
Time Frame Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description

The pharmacokinetic (PK) evaluable population includes participants with stable baseline renal function (Arms 1–4) who completed all protocol-specified treatment and PK blood sample collection through Cycle 1, Day 16. In Group 5, only samples collected before dialysis were included.

CL could not be estimated for 11 patients in the PK population.

Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 6 6 3 4 5
Mean (Standard Deviation)
Unit of Measure: liters/hour
151  (79.3) 113  (40.7) 288  (264) 170  (58.4) 170  (60.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carfilzomib – Normal RF, Carfilzomib – Mild RI, Carfilzomib – Moderate RI, Carfilzomib – Severe RI
Comments

In order to estimate a possible effect of renal function, the relationship between the clearance of carfilzomib and creatinine clearance (CrCl) was explored using a mixed-effects model that included CrCl.

The slope of the regression of CL as a function of CrCL at Cycle 1, Day 1 was evaluated using a linear regression model that included CrCL as continuous variables (excluding the hemodialysis group).

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4114
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.607
Confidence Interval (2-Sided) 95%
-2.129 to 0.914
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Clearance (CL) of Carfilzomib on Day 15 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 5 5 3 1 5
Mean (Standard Deviation)
Unit of Measure: liters/hour
660  (1134) 115  (34.7) 119  (16.5) 110 [1]   (NA) 114  (61.2)
[1]
Can not be calculated for a sample of 1
3.Secondary Outcome
Title Clearance (CL) of Carfilzomib on Day 15 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, Day 15, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 0 0 1 1 0
Mean (Standard Deviation)
Unit of Measure: liters/hour
679 [1]   (NA) 46.6 [1]   (NA)
[1]
Cannot be calculated for a sample of 1
4.Secondary Outcome
Title Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 8 9 5 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
2077
(91.4%)
1623
(161%)
1840
(92.4%)
1231
(139%)
1539
(92.7%)
5.Secondary Outcome
Title Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 7 8 5 4 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1768
(179%)
2406
(52.3%)
2627
(31.8%)
1914
(99.8%)
3236
(34.4%)
6.Secondary Outcome
Title Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 0 0 1 2 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
244 [1] 
(NA%)
3064
(3.9%)
[1]
Cannot be calculated for a sample of 1
7.Secondary Outcome
Title Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; AUCinf could not be estimated for 11 participants in the PK population who did not have adequate PK data.
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 6 6 3 4 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
233
(51.6%)
241
(32.4%)
145
(111%)
172
(35.6%)
193
(55.2%)
8.Secondary Outcome
Title Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 5 5 3 1 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
127
(240%)
236
(44.3%)
257
(10.9%)
218 [1] 
(NA%)
272
(46.4%)
[1]
Cannot be calculated for a sample of 1
9.Secondary Outcome
Title Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 0 0 1 1 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
48.6 [1] 
(NA%)
579 [1] 
(NA%)
[1]
Cannot be calculated for a sample of 1
10.Secondary Outcome
Title Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 8 9 5 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
187
(75.3%)
194
(67.6%)
199
(91.3%)
135
(65.5%)
195
(65.3%)
11.Secondary Outcome
Title Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 7 8 5 4 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
159
(186%)
289
(58.5%)
371
(55.2%)
343
(53.1%)
264
(41.7%)
12.Secondary Outcome
Title Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 0 0 1 2 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*ng/mL
47.3 [1] 
(NA%)
345
(83.6%)
[1]
Cannot be calculated for a sample of 1
13.Secondary Outcome
Title Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1
Hide Description The percentage of carfilzomib excreted in urine was calculated as the total amount excreted over 24 hours/dose.
Time Frame Cycle 1, Day 1, 0-5 and 5-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1-4 with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 8 8 7 5 0
Mean (Standard Deviation)
Unit of Measure: percentage of carfilzomib dose
0.490  (0.316) 0.429  (0.271) 0.160  (0.101) 0.226  (0.0921)
14.Secondary Outcome
Title Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1
Hide Description The percentage of carfilzomib excreted in urine was calculated as the total amount excreted over 24 hours/dose.
Time Frame Cycle 1, Day 15, 0-5 and 5-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1-4 with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 7 6 5 4 0
Mean (Standard Deviation)
Unit of Measure: percentage of carfilzomib dose
0.446  (0.357) 0.428  (0.262) 0.202  (0.116) 0.168  (0.0670)
15.Secondary Outcome
Title Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1
Hide Description The percentage of the metabolites of carfilzomib (PR-389/M14 and PR-413/M15) excreted in urine was calculated as the total amount excreted over 24 hours/dose.
Time Frame Cycle 1, Day 1, 0-5 and 5-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1-4 with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 8 9 7 5 0
Mean (Standard Deviation)
Unit of Measure: percentage of carfilzomib dose
M14 33.1  (13.1) 25.0  (4.81) 21.7  (7.59) 19.2  (4.36)
M15 1.93  (1.12) 1.42  (0.314) 0.776  (0.387) 0.578  (0.230)
16.Secondary Outcome
Title Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1
Hide Description The percentage of the metabolites of carfilzomib (PR-389/M14 and PR-413/M15) excreted in urine was calculated as the total amount excreted over 24 hours/dose.
Time Frame Cycle 1, Day 15, 0-5 and 5-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1-4 with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 7 6 5 4 0
Mean (Standard Deviation)
Unit of Measure: percentage of carfilzomib dose
M14 30.6  (11.6) 27.0  (8.47) 22.0  (6.89) 17.0  (4.67)
M15 1.91  (1.03) 1.55  (0.602) 0.856  (0.377) 0.475  (0.249)
17.Secondary Outcome
Title Plasma Protein Binding (PPB) of Carfilzomib
Hide Description The plasma protein binding (PPB) of carfilzomib in plasma samples was determined using a rapid equilibrium dialysis (RED) device. Data are averages of the 3 time points (Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 15).
Time Frame End of injection and 5 minutes post-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 15
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Hide Analysis Population Description
Participants with available data
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 11 8 9 9 7
Mean (Standard Deviation)
Unit of Measure: percentage of carfilzomib bound
End of Injection 97.8  (0.6) 97.6  (1.5) 98.4  (0.4) 98.2  (0.5) 97.6  (0.7)
5 minutes after injection 98.1  (0.5) 97.6  (1.6) 98.2  (1.5) 98.1  (0.8) 98.2  (0.4)
18.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description

ORR is defined as the percentage of participants with a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Uniform Response Criteria for Multiple Myeloma.

sCR: CR as defined below plus normal serum free light chain (sFLC) ratio and absence of clonal plasma cells in bone marrow by immunohistochemistry or immunofluorescence; CR: absence of M-protein in serum and urine confirmed by immunofixation and < 5% plasma cells in the bone marrow; VGPR: serum and urine M-proteins detectable by immunofixation, but not by electrophoresis or a ≥ 90% reduction in serum M-protein from baseline, plus a urine M-protein level of < 100 mg/24 hours; PR: reduction of M-protein in serum of ≥ 50% and in urine of ≥ 90% from baseline. If serum and urine M-protein were not measureable at baseline, a ≥ 50% decrease in the difference between involved and uninvolved sFLC levels from baseline.

Time Frame From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.
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Hide Analysis Population Description
The response evaluable population included all participants with measurable disease and a baseline and at least 1 post-baseline disease assessment or who discontinued study treatment due to a related adverse event prior to obtaining an on-study disease assessment.
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 11 11 9 8 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.2
(2.3 to 51.8)
27.3
(6.0 to 61.0)
22.2
(2.8 to 60.0)
25.0
(3.2 to 65.1)
37.5
(8.5 to 75.5)
19.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description Clinical benefit rate is defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a reduction of M-protein in serum of 25% to 49% and in urine of 50% to 89% from baseline, maintained for at least 6 weeks.
Time Frame From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.
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Hide Analysis Population Description
The response evaluable population
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 11 11 9 8 8
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27.3
(6.0 to 61.0)
36.4
(10.9 to 69.2)
22.2
(2.8 to 60.0)
37.5
(8.5 to 75.5)
37.5
(8.5 to 75.5)
20.Secondary Outcome
Title Duration of Response
Hide Description

Duration of Response is defined as the time from first evidence of PR or better to confirmation of disease progression or death.

Progressive disease was defined as any of the following:

  • An increase of more than 25% from nadir in any one of the following:

    • M-protein in serum (the absolute increase had to be ≥ 0.5 g/dL);
    • Urine (the absolute increase had to be ≥ 200 mg/24 hours);
    • The difference between involved and uninvolved sFLC (the absolute increase in the concentration of involved light chain had to be > 10 mg/dL);
    • ≥ 10% bone marrow infiltration by plasma cells;
  • Increased size of pre-existing bone lesions or plasmacytomas or new bone lesions or plasmacytomas.

Median duration of response was estimated using the Kaplan-Meier method.

Time Frame Participants were followed for disease progression for up to 2 years.
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Hide Analysis Population Description
Response Evaluable Population with a best overall response of sCR, CR, VGPR, or PR.
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 2 3 2 2 3
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(2.0 to NA)
NA [1] 
(4.2 to NA)
14.8
(2.3 to 27.4)
NA [1] 
(7.9 to NA)
7.9
(6.5 to 8.5)
[1]
Could not be estimated due to the low number of events
21.Secondary Outcome
Title Time to Progression (TTP)
Hide Description Time to Progression is defined as the time from first dose of carfilzomib to disease progression. Median TTP was estimated using Kaplan-Meier methods.
Time Frame Participants were followed for disease progression for up to 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Response Evaluable Population
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description:

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Overall Number of Participants Analyzed 11 11 9 8 8
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(2.8 to 9.2)
5.6
(0.5 to 7.9)
2.8
(1.0 to 29.2)
9.6
(1.0 to 11.8)
6.5
(2.8 to 11.3)
Time Frame From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 121 days.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Hide Arm/Group Description

Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) > 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants with severe renal impairment (CrCL < 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles.

If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

All-Cause Mortality
Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/12 (41.67%)   8/12 (66.67%)   10/10 (100.00%)   6/8 (75.00%)   8/8 (100.00%) 
Blood and lymphatic system disorders           
Febrile neutropenia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Cardiac disorders           
Angina pectoris  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Angina unstable  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Atrial fibrillation  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Atrial flutter  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Cardiac failure congestive  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  2/8 (25.00%)  0/8 (0.00%) 
Right ventricular failure  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Diarrhoea  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Hiatus hernia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nausea  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Small intestinal obstruction  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Vomiting  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
General disorders           
Disease progression  1  0/12 (0.00%)  3/12 (25.00%)  0/10 (0.00%)  1/8 (12.50%)  3/8 (37.50%) 
Non-cardiac chest pain  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Oedema peripheral  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pyrexia  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Hepatobiliary disorders           
Venoocclusive liver disease  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Immune system disorders           
Amyloidosis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Infections and infestations           
Bronchitis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Bronchitis viral  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Cellulitis  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Central line infection  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Gastroenteritis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Influenza  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  1/8 (12.50%) 
Injection site cellulitis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Paronychia  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pneumonia  1  2/12 (16.67%)  2/12 (16.67%)  4/10 (40.00%)  2/8 (25.00%)  0/8 (0.00%) 
Pneumonia bacterial  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Respiratory tract infection bacterial  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Sepsis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Septic shock  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Streptococcal bacteraemia  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Upper respiratory tract infection  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Urinary tract infection  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  1/8 (12.50%) 
Urosepsis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Investigations           
Blood alkaline phosphatase increased  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood creatinine increased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  2/8 (25.00%)  0/8 (0.00%) 
Hypercalcaemia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypophosphataemia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders           
Pathological fracture  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Plasmacytoma  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nervous system disorders           
Headache  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Spinal cord compression  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Syncope  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Psychiatric disorders           
Depression  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Mental status changes  1  0/12 (0.00%)  1/12 (8.33%)  3/10 (30.00%)  0/8 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders           
Renal failure  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  0/8 (0.00%) 
Renal failure acute  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  2/8 (25.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Chronic obstructive pulmonary disease  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dyspnoea  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Pleural effusion  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Pneumonia aspiration  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Pulmonary embolism  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pulmonary hypertension  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Respiratory alkalosis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Respiratory failure  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  2/8 (25.00%) 
Vascular disorders           
Deep vein thrombosis  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Superior vena caval occlusion  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Carfilzomib – Normal RF Carfilzomib – Mild RI Carfilzomib – Moderate RI Carfilzomib – Severe RI Carfilzomib – Dialysis
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   12/12 (100.00%)   10/10 (100.00%)   8/8 (100.00%)   8/8 (100.00%) 
Blood and lymphatic system disorders           
Anaemia  1  6/12 (50.00%)  7/12 (58.33%)  7/10 (70.00%)  5/8 (62.50%)  5/8 (62.50%) 
Hypocoagulable state  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Leukopenia  1  1/12 (8.33%)  1/12 (8.33%)  2/10 (20.00%)  0/8 (0.00%)  1/8 (12.50%) 
Lymphadenopathy  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Lymphopenia  1  4/12 (33.33%)  4/12 (33.33%)  2/10 (20.00%)  2/8 (25.00%)  4/8 (50.00%) 
Neutropenia  1  2/12 (16.67%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Thrombocytopenia  1  4/12 (33.33%)  6/12 (50.00%)  5/10 (50.00%)  3/8 (37.50%)  5/8 (62.50%) 
Cardiac disorders           
Angina pectoris  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Arrhythmia  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Atrial fibrillation  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  2/8 (25.00%) 
Bradycardia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Cardiac failure acute  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Cardiac failure congestive  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Dilatation atrial  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Tachycardia  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  2/8 (25.00%)  1/8 (12.50%) 
Ear and labyrinth disorders           
Ear congestion  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Vertigo positional  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Eye disorders           
Conjunctivitis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Diplopia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dry eye  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Eye pain  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Keratitis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Gastrointestinal disorders           
Abdominal discomfort  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Abdominal distension  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Abdominal pain  1  1/12 (8.33%)  2/12 (16.67%)  2/10 (20.00%)  0/8 (0.00%)  4/8 (50.00%) 
Abdominal pain upper  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Bowel sounds abnormal  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Colitis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Colonic haemorrhage  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Colonic polyp  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Constipation  1  3/12 (25.00%)  6/12 (50.00%)  5/10 (50.00%)  2/8 (25.00%)  3/8 (37.50%) 
Diarrhoea  1  5/12 (41.67%)  6/12 (50.00%)  5/10 (50.00%)  2/8 (25.00%)  4/8 (50.00%) 
Dry mouth  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dyspepsia  1  1/12 (8.33%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  0/8 (0.00%) 
Flatulence  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Gastrooesophageal reflux disease  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Haemorrhoids  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Hypoaesthesia oral  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Impaired gastric emptying  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Inguinal hernia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Mouth haemorrhage  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Mouth ulceration  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nausea  1  6/12 (50.00%)  4/12 (33.33%)  6/10 (60.00%)  1/8 (12.50%)  4/8 (50.00%) 
Oral pain  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Toothache  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Vomiting  1  2/12 (16.67%)  1/12 (8.33%)  3/10 (30.00%)  0/8 (0.00%)  3/8 (37.50%) 
General disorders           
Asthenia  1  1/12 (8.33%)  1/12 (8.33%)  3/10 (30.00%)  2/8 (25.00%)  2/8 (25.00%) 
Catheter site haematoma  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Catheter site inflammation  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Catheter site related reaction  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Chest discomfort  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Chest pain  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Chills  1  1/12 (8.33%)  2/12 (16.67%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Disease progression  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  2/8 (25.00%)  0/8 (0.00%) 
Face oedema  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Facial pain  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Fatigue  1  9/12 (75.00%)  9/12 (75.00%)  6/10 (60.00%)  4/8 (50.00%)  4/8 (50.00%) 
Generalised oedema  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypothermia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Infusion related reaction  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Infusion site pain  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  1/8 (12.50%) 
Local swelling  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Mass  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Mucosal inflammation  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Non-cardiac chest pain  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Oedema  1  2/12 (16.67%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Oedema peripheral  1  4/12 (33.33%)  2/12 (16.67%)  3/10 (30.00%)  3/8 (37.50%)  1/8 (12.50%) 
Pain  1  0/12 (0.00%)  3/12 (25.00%)  4/10 (40.00%)  0/8 (0.00%)  4/8 (50.00%) 
Pitting oedema  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Pyrexia  1  3/12 (25.00%)  2/12 (16.67%)  3/10 (30.00%)  0/8 (0.00%)  4/8 (50.00%) 
Tenderness  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Immune system disorders           
Seasonal allergy  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Infections and infestations           
Bacteraemia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Cellulitis  1  2/12 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Herpes simplex  1  2/12 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Herpes zoster  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Influenza  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nasopharyngitis  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Oral candidiasis  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Paronychia  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pneumonia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Pseudomonas infection  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Respiratory syncytial virus infection  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Rhinitis  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Sepsis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  3/8 (37.50%) 
Sinusitis  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Staphylococcal infection  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Tinea pedis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Upper respiratory tract infection  1  2/12 (16.67%)  1/12 (8.33%)  1/10 (10.00%)  3/8 (37.50%)  2/8 (25.00%) 
Urinary tract infection  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Urinary tract infection pseudomonal  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications           
Arthropod bite  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Contusion  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Limb injury  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Post procedural haemorrhage  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Post procedural vomiting  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Postoperative fever  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Procedural pain  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Skin injury  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Investigations           
Abdominal bruit  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Activated partial thromboplastin time prolonged  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  2/8 (25.00%) 
Alanine aminotransferase increased  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Aspartate aminotransferase increased  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Blood albumin decreased  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Blood alkaline phosphatase increased  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood calcium increased  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood creatinine decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Blood creatinine increased  1  1/12 (8.33%)  2/12 (16.67%)  5/10 (50.00%)  1/8 (12.50%)  2/8 (25.00%) 
Blood glucose decreased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood glucose increased  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood magnesium decreased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood phosphorus decreased  1  1/12 (8.33%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  1/8 (12.50%) 
Blood phosphorus increased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood potassium decreased  1  3/12 (25.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  2/8 (25.00%) 
Blood potassium increased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood pressure diastolic decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Blood pressure increased  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood sodium decreased  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood uric acid increased  1  0/12 (0.00%)  2/12 (16.67%)  3/10 (30.00%)  1/8 (12.50%)  3/8 (37.50%) 
Breath sounds abnormal  1  0/12 (0.00%)  2/12 (16.67%)  3/10 (30.00%)  1/8 (12.50%)  0/8 (0.00%) 
Carbon dioxide decreased  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Cardiac murmur  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Ejection fraction decreased  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Haemoglobin decreased  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  1/8 (12.50%) 
International normalised ratio increased  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Lymphocyte count decreased  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Occult blood positive  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Platelet count decreased  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Respiratory rate decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Troponin increased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Urine output decreased  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  0/8 (0.00%) 
Weight decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
White blood cell count decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Metabolism and nutrition disorders           
Acidosis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Anorexia  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Decreased appetite  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dehydration  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypercalcaemia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Hyperglycaemia  1  3/12 (25.00%)  1/12 (8.33%)  2/10 (20.00%)  2/8 (25.00%)  2/8 (25.00%) 
Hyperkalaemia  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  2/8 (25.00%) 
Hypermagnesaemia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  1/8 (12.50%)  0/8 (0.00%) 
Hypernatraemia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hyperphosphataemia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  2/8 (25.00%) 
Hyperuricaemia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypoalbuminaemia  1  1/12 (8.33%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypocalcaemia  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  1/8 (12.50%)  2/8 (25.00%) 
Hypoglycaemia  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  1/8 (12.50%)  2/8 (25.00%) 
Hypokalaemia  1  5/12 (41.67%)  3/12 (25.00%)  4/10 (40.00%)  2/8 (25.00%)  4/8 (50.00%) 
Hypomagnesaemia  1  3/12 (25.00%)  4/12 (33.33%)  4/10 (40.00%)  2/8 (25.00%)  3/8 (37.50%) 
Hyponatraemia  1  0/12 (0.00%)  0/12 (0.00%)  2/10 (20.00%)  1/8 (12.50%)  0/8 (0.00%) 
Hypophosphataemia  1  1/12 (8.33%)  1/12 (8.33%)  2/10 (20.00%)  0/8 (0.00%)  1/8 (12.50%) 
Lactic acidosis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Overweight  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/12 (8.33%)  1/12 (8.33%)  4/10 (40.00%)  0/8 (0.00%)  0/8 (0.00%) 
Back pain  1  5/12 (41.67%)  3/12 (25.00%)  1/10 (10.00%)  1/8 (12.50%)  2/8 (25.00%) 
Bone pain  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  1/8 (12.50%) 
Chest wall pain  1  3/12 (25.00%)  1/12 (8.33%)  2/10 (20.00%)  2/8 (25.00%)  1/8 (12.50%) 
Joint range of motion decreased  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Joint swelling  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Muscle spasms  1  3/12 (25.00%)  2/12 (16.67%)  1/10 (10.00%)  1/8 (12.50%)  2/8 (25.00%) 
Muscular weakness  1  0/12 (0.00%)  2/12 (16.67%)  2/10 (20.00%)  1/8 (12.50%)  2/8 (25.00%) 
Myalgia  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Neck pain  1  1/12 (8.33%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nodule on extremity  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Pain in extremity  1  5/12 (41.67%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  2/8 (25.00%) 
Pain in jaw  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pathological fracture  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  3/8 (37.50%) 
Rotator cuff syndrome  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Sensation of heaviness  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Shoulder pain  1  2/12 (16.67%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  1/8 (12.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Bone neoplasm  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nervous system disorders           
Aphasia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Areflexia  1  1/12 (8.33%)  2/12 (16.67%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Balance disorder  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Depressed level of consciousness  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Diplegia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Disturbance in attention  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Dizziness  1  2/12 (16.67%)  2/12 (16.67%)  2/10 (20.00%)  1/8 (12.50%)  1/8 (12.50%) 
Dysgeusia  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Headache  1  5/12 (41.67%)  2/12 (16.67%)  2/10 (20.00%)  0/8 (0.00%)  2/8 (25.00%) 
Hypoaesthesia  1  2/12 (16.67%)  3/12 (25.00%)  1/10 (10.00%)  2/8 (25.00%)  1/8 (12.50%) 
Hyporeflexia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Lethargy  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Neuropathic pain  1  3/12 (25.00%)  4/12 (33.33%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Neuropathy  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  1/8 (12.50%) 
Neuropathy peripheral  1  2/12 (16.67%)  1/12 (8.33%)  2/10 (20.00%)  2/8 (25.00%)  0/8 (0.00%) 
Paraesthesia  1  2/12 (16.67%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Post herpetic neuralgia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Sinus headache  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Somnolence  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Spinal cord compression  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Syncope  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Psychiatric disorders           
Anxiety  1  1/12 (8.33%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Delirium  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Depression  1  2/12 (16.67%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  2/8 (25.00%) 
Insomnia  1  3/12 (25.00%)  1/12 (8.33%)  2/10 (20.00%)  2/8 (25.00%)  0/8 (0.00%) 
Mental status changes  1  0/12 (0.00%)  1/12 (8.33%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Mood altered  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Renal and urinary disorders           
Azotaemia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  2/8 (25.00%)  0/8 (0.00%) 
Incontinence  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nephrolithiasis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Nocturia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  2/8 (25.00%)  0/8 (0.00%) 
Pollakiuria  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Renal failure  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Renal failure chronic  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Renal impairment  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Urinary tract pain  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Urine flow decreased  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Reproductive system and breast disorders           
Erectile dysfunction  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Atelectasis  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Cough  1  2/12 (16.67%)  2/12 (16.67%)  4/10 (40.00%)  1/8 (12.50%)  1/8 (12.50%) 
Dyspnoea  1  6/12 (50.00%)  3/12 (25.00%)  4/10 (40.00%)  3/8 (37.50%)  3/8 (37.50%) 
Dyspnoea exacerbated  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dyspnoea exertional  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Epistaxis  1  1/12 (8.33%)  1/12 (8.33%)  2/10 (20.00%)  0/8 (0.00%)  2/8 (25.00%) 
Hiccups  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hypoxia  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nasal congestion  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Nasal dryness  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Pharyngolaryngeal pain  1  2/12 (16.67%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  2/8 (25.00%) 
Pleural effusion  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Productive cough  1  1/12 (8.33%)  2/12 (16.67%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Pulmonary hypertension  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Rales  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Rhinalgia  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Sinus congestion  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Sneezing  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Tachypnoea  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Throat irritation  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Wheezing  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders           
Acne  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Alopecia  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Blood blister  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Decubitus ulcer  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Dermatitis  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Dry skin  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Ecchymosis  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Erythema  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Hyperhidrosis  1  0/12 (0.00%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Night sweats  1  1/12 (8.33%)  0/12 (0.00%)  2/10 (20.00%)  0/8 (0.00%)  0/8 (0.00%) 
Petechiae  1  1/12 (8.33%)  2/12 (16.67%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Pruritus  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  1/8 (12.50%) 
Rash  1  1/12 (8.33%)  0/12 (0.00%)  2/10 (20.00%)  1/8 (12.50%)  0/8 (0.00%) 
Rash macular  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Rash pruritic  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Skin exfoliation  1  0/12 (0.00%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Skin lesion  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Skin tightness  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Swelling face  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Vascular disorders           
Deep vein thrombosis  1  1/12 (8.33%)  0/12 (0.00%)  1/10 (10.00%)  0/8 (0.00%)  0/8 (0.00%) 
Haematoma  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Hypertension  1  1/12 (8.33%)  0/12 (0.00%)  2/10 (20.00%)  1/8 (12.50%)  2/8 (25.00%) 
Hypotension  1  0/12 (0.00%)  1/12 (8.33%)  0/10 (0.00%)  0/8 (0.00%)  4/8 (50.00%) 
Pallor  1  1/12 (8.33%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Superior vena caval occlusion  1  0/12 (0.00%)  0/12 (0.00%)  0/10 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen, Inc.
Phone: 866-572-6436
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00721734     History of Changes
Other Study ID Numbers: PX-171-005
First Submitted: July 22, 2008
First Posted: July 24, 2008
Results First Submitted: November 2, 2015
Results First Posted: December 9, 2015
Last Update Posted: May 2, 2017