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Trial record 13 of 21 for:    stem cell kidney | ( Map: Canada )

Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease

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: NCT01949532
Recruitment Status : Completed
First Posted : September 24, 2013
Results First Posted : May 4, 2016
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Relapsed Multiple Myeloma
End-stage Renal Disease
Intervention Drug: Carfilzomib
Enrollment 26
Recruitment Details

Participants were enrolled at 13 investigative study centers (6 in the United States, 2 in Canada, and 5 in Australia) from 29 January 2014 to 25 March 2015.

This study is ongoing, results are reported as of the data cut-off date of 12 October 2015.

Pre-assignment Details Participants with relapsed multiple myeloma were enrolled into cohorts according to renal function (normal creatinine clearance (CrCl) or end-stage renal disease (ESRD; patients on hemodialysis)). Renal function was based on calculated CrCl using the Cockcroft-Gault formula at baseline.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description Participants with normal renal function (creatinine clearance [CrCl] ≥ 75 mL/min) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death. Participants with end-stage renal disease (on hemodialysis) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.
Period Title: Overall Study
Started 15 11
Completed 12 8
Not Completed 3 3
Reason Not Completed
On-study at the Data Cut-off Date             3             3
Arm/Group Title Normal Renal Function End Stage Renal Disease Total
Hide Arm/Group Description Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Total of all reporting groups
Overall Number of Baseline Participants 15 11 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 11 participants 26 participants
64.8  (8.1) 62.8  (7.9) 64.0  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 11 participants 26 participants
Female
5
  33.3%
6
  54.5%
11
  42.3%
Male
10
  66.7%
5
  45.5%
15
  57.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 11 participants 26 participants
Hispanic or Latino
1
   6.7%
0
   0.0%
1
   3.8%
Not Hispanic or Latino
14
  93.3%
9
  81.8%
23
  88.5%
Unknown or Not Reported
0
   0.0%
2
  18.2%
2
   7.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 11 participants 26 participants
Asian 1 0 1
Black 1 1 2
White 12 9 21
Other 1 0 1
Not Reported 0 1 1
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 11 participants 26 participants
0 (Fully active) 5 3 8
1 (Restrictive but ambulatory) 10 7 17
2 (Ambulatory but unable to work) 0 1 1
[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 Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description Carfilzomib plasma concentrations for pharmacokinetic (PK) analyses were measured by liquid chromatography with tandem mass spectrometry. The lower limit of quantitation (LLOQ) for the assay was 0.3 ng/mL.
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. The PK evaluable population is defined as participants with sufficient carfilzomib plasma concentration versus time data for the estimation of PK parameters by non-compartmental analysis on cycle 1, day 16 and/or cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
563
(41.9%)
747
(143.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, End Stage Renal Disease
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 132.75
Confidence Interval (2-Sided) 90%
70.60 to 249.63
Estimation Comments The point estimates of the geometric mean ratios for the PK parameters were calculated by exponentiation of the differences in the least-squares means between the renal impairment group (test) and participants with normal renal function (reference).
2.Primary Outcome
Title Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
563
(41.8%)
752
(144.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, End Stage Renal Disease
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of geometric means
Estimated Value 133.62
Confidence Interval (2-Sided) 90%
70.93 to 251.73
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1389
(26.8%)
1567
(128.8%)
4.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Median (Full Range)
Unit of Measure: hours
0.467
(0.250 to 0.733)
0.467
(0.250 to 0.583)
5.Secondary Outcome
Title Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Median (Full Range)
Unit of Measure: hours
0.341
(0.111 to 0.498)
1.25
(0.0632 to 3.31)
6.Secondary Outcome
Title Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters/hour
179
(38.9%)
134
(136.9%)
7.Secondary Outcome
Title Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
0.135
(62.6%)
0.245
(79.9%)
8.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Hide Description [Not Specified]
Time Frame Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters
24.1
(44.8%)
32.8
(133.9%)
9.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
344
(24.8%)
480
(36.0%)
10.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants for whom the coefficient of correlation (R²) was < 0.8 were excluded.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 11 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
347
(26.3%)
479
(46.6%)
11.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
819
(29.8%)
1022
(37.2%)
12.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Median (Full Range)
Unit of Measure: hours
0.583
(0.467 to 0.733)
0.467
(0.233 to 0.750)
13.Secondary Outcome
Title Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants with a coefficient of correlation (R²) < 0.8 were excluded.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 11 6
Median (Full Range)
Unit of Measure: hours
0.387
(0.0938 to 0.599)
0.992
(0.918 to 16.0)
14.Secondary Outcome
Title Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters/hour
146
(23.0%)
93
(56.8%)
15.Secondary Outcome
Title Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants with a coefficient of correlation (R²) < 0.8 were excluded.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 11 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
0.222
(16.6%)
0.426
(152.2%)
16.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population for cycle 1, day 16. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters
32.0
(29.7%)
53.0
(185.5%)
17.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. "n" indicates the number of participants included in the analyses at each time point.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16 (n = 13, 9)
320
(32.8%)
1486
(32.3%)
Cycle 2, Day 1 (n = 10, 8)
584
(17.5%)
2086
(132.8%)
18.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded. AUC0-∞ could not be calculated for the ESRD group as the extrapolated portion (AUCextr) was greater than 20% in all participants.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16
355
(25.1%)
Cycle 2, Day 1
650
(22.5%)
19.Secondary Outcome
Title Maximum Observed Plasma Concentration for Metabolite PR-389/M14
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1, Day 16 (n = 13, 9)
153
(25.4%)
413
(32.9%)
Cycle 2, Day 1 (n = 10, 8)
302
(16.5%)
595
(128.4%)
20.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16 (n = 13, 9)
1.00
(0.750 to 1.13)
1.50
(1.00 to 2.67)
Cycle 2, Day 1 (n = 10, 8)
0.983
(0.583 to 1.02)
2.00
(1.45 to 4.47)
21.Secondary Outcome
Title Terminal Half-life (T½) of Metabolite PR-389/M14
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded. T½ could not be calculated for the ESRD group as the extrapolated portion (AUCextr) was greater than 20% in all participants.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 10 0
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16
1.46
(0.975 to 1.73)
Cycle 2, Day 1
1.10
(0.903 to 1.70)
22.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16 (n = 13, 9)
33.4
(53.9%)
54.6
(45.0%)
Cycle 2, Day 1 (n = 10, 8)
60.3
(48.4%)
86.3
(199.1%)
23.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16 (n = 13, 7)
36.2
(54.1%)
66.4
(48.7%)
Cycle 2, Day 1 (n = 10, 5)
63.8
(48.0%)
131
(35.8%)
24.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1, Day 16 (n = 13, 9)
20.7
(43.5%)
25.9
(42.5%)
Cycle 2, Day 1 (n = 10, 8)
40.2
(38.5%)
42.3
(163.9%)
25.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16 (n = 13, 9)
0.833
(0.683 to 1.00)
0.767
(0.733 to 1.05)
Cycle 2, Day 1 (n = 10, 8)
0.667
(0.250 to 1.00)
0.750
(0.717 to 1.52)
26.Secondary Outcome
Title Terminal Half-life (T½) of Metabolite PR-413/M15
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population. One participant was excluded due to samples taken from the infusion arm, distal to the infusion site. Participants for whom the extrapolated portion of AUC0-∞ was > 20% were excluded.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 7
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16 (n = 13, 7)
1.07
(0.544 to 1.33)
1.41
(1.30 to 1.86)
Cycle 2, Day 1 (n = 10, 5)
0.962
(0.802 to 1.21)
1.37
(1.04 to 1.44)
27.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16 (n = 13, 9)
82.8
(53.1%)
86.8
(44.3%)
Cycle 2, Day 1 (n = 10, 8)
147
(52.8%)
138
(126.6%)
28.Secondary Outcome
Title Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Cycle 1, Day 16 (n = 13, 9)
84.4
(52.4%)
89.6
(42.8%)
Cycle 2, Day 1 (n = 10, 8)
148
(51.7%)
139
(125.1%)
29.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1, Day 16 (n = 13, 9)
93.4
(40.2%)
90.4
(48.0%)
Cycle 2, Day 1 (n = 10, 8)
180
(40.5%)
151
(129.7%)
30.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16 (n = 13, 9)
0.617
(0.467 to 1.00)
0.600
(0.467 to 0.917)
Cycle 2, Day 1 (n = 10, 8)
0.525
(0.250 to 0.617)
0.533
(0.467 to 0.750)
31.Secondary Outcome
Title Terminal Half-life (T½) of Metabolite PR-519/M16
Hide Description [Not Specified]
Time Frame Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
PK evaluable population; one participant was excluded due to samples taken from the infusion arm, distal to the infusion site.
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 13 9
Median (Full Range)
Unit of Measure: hours
Cycle 1, Day 16 (n = 13, 9)
0.705
(0.473 to 0.993)
0.721
(0.518 to 1.42)
Cycle 2, Day 1 (n = 10, 8)
0.617
(0.555 to 0.673)
0.687
(0.473 to 0.933)
32.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

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

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

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

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

Time Frame From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description:
Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
Overall Number of Participants Analyzed 15 11
Measure Type: Number
Unit of Measure: participants
Any adverse event 15 11
Adverse event ≥ Grade 3 12 9
Serious adverse event 10 9
AE leading to discontinuation of carfilzomib 6 0
Fatal adverse events 2 1
Treatment-related adverse events 12 8
Treatment-related adverse event ≥ Grade 3 7 6
Serious treatment-related adverse event 5 2
TRAE leading to discontinuation of carfilzomib 4 0
Treatment-related fatal adverse events 0 0
Time Frame From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Normal Renal Function End Stage Renal Disease
Hide Arm/Group Description Participants with normal renal function received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants with ESRD received carfilzomib 20 mg/m² IV on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles.
All-Cause Mortality
Normal Renal Function End Stage Renal Disease
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Normal Renal Function End Stage Renal Disease
Affected / at Risk (%) Affected / at Risk (%)
Total   10/15 (66.67%)   9/11 (81.82%) 
Blood and lymphatic system disorders     
Anaemia  1  0/15 (0.00%)  2/11 (18.18%) 
Coagulopathy  1  0/15 (0.00%)  1/11 (9.09%) 
Immune thrombocytopenic purpura  1  0/15 (0.00%)  1/11 (9.09%) 
Leukocytosis  1  0/15 (0.00%)  1/11 (9.09%) 
Microangiopathic haemolytic anaemia  1  1/15 (6.67%)  0/11 (0.00%) 
Thrombocytopenia  1  1/15 (6.67%)  1/11 (9.09%) 
Cardiac disorders     
Atrial fibrillation  1  1/15 (6.67%)  1/11 (9.09%) 
Cardio-respiratory arrest  1  1/15 (6.67%)  0/11 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  0/15 (0.00%)  1/11 (9.09%) 
Mouth ulceration  1  0/15 (0.00%)  1/11 (9.09%) 
General disorders     
Asthenia  1  0/15 (0.00%)  2/11 (18.18%) 
Chills  1  0/15 (0.00%)  1/11 (9.09%) 
Death  1  1/15 (6.67%)  1/11 (9.09%) 
Pyrexia  1  2/15 (13.33%)  2/11 (18.18%) 
Hepatobiliary disorders     
Cholecystitis  1  1/15 (6.67%)  0/11 (0.00%) 
Infections and infestations     
Influenza  1  0/15 (0.00%)  1/11 (9.09%) 
Lower respiratory tract infection  1  1/15 (6.67%)  2/11 (18.18%) 
Pneumonia  1  3/15 (20.00%)  2/11 (18.18%) 
Pneumonia klebsiella  1  1/15 (6.67%)  0/11 (0.00%) 
Respiratory syncytial virus infection  1  0/15 (0.00%)  1/11 (9.09%) 
Respiratory tract infection viral  1  0/15 (0.00%)  1/11 (9.09%) 
Urosepsis  1  1/15 (6.67%)  0/11 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  1/15 (6.67%)  0/11 (0.00%) 
Procedural hypotension  1  0/15 (0.00%)  1/11 (9.09%) 
Investigations     
Troponin increased  1  1/15 (6.67%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  0/15 (0.00%)  1/11 (9.09%) 
Nervous system disorders     
Dizziness  1  0/15 (0.00%)  1/11 (9.09%) 
Psychiatric disorders     
Delirium  1  1/15 (6.67%)  0/11 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  2/15 (13.33%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute interstitial pneumonitis  1  1/15 (6.67%)  0/11 (0.00%) 
Dyspnoea  1  1/15 (6.67%)  0/11 (0.00%) 
Hypoxia  1  1/15 (6.67%)  1/11 (9.09%) 
Respiratory distress  1  1/15 (6.67%)  0/11 (0.00%) 
Vascular disorders     
Haematoma  1  0/15 (0.00%)  1/11 (9.09%) 
Hypotension  1  0/15 (0.00%)  2/11 (18.18%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Normal Renal Function End Stage Renal Disease
Affected / at Risk (%) Affected / at Risk (%)
Total   14/15 (93.33%)   10/11 (90.91%) 
Blood and lymphatic system disorders     
Anaemia  1  8/15 (53.33%)  5/11 (45.45%) 
Neutropenia  1  2/15 (13.33%)  0/11 (0.00%) 
Thrombocytopenia  1  7/15 (46.67%)  1/11 (9.09%) 
Cardiac disorders     
Angina pectoris  1  1/15 (6.67%)  0/11 (0.00%) 
Cardiovascular disorder  1  0/15 (0.00%)  1/11 (9.09%) 
Sinus tachycardia  1  0/15 (0.00%)  1/11 (9.09%) 
Tachycardia  1  1/15 (6.67%)  1/11 (9.09%) 
Ear and labyrinth disorders     
Ear congestion  1  1/15 (6.67%)  0/11 (0.00%) 
Hypoacusis  1  0/15 (0.00%)  1/11 (9.09%) 
Meniere's disease  1  0/15 (0.00%)  1/11 (9.09%) 
Vertigo  1  0/15 (0.00%)  1/11 (9.09%) 
Eye disorders     
Cataract  1  0/15 (0.00%)  1/11 (9.09%) 
Exophthalmos  1  1/15 (6.67%)  0/11 (0.00%) 
Eye discharge  1  0/15 (0.00%)  1/11 (9.09%) 
Eye inflammation  1  1/15 (6.67%)  0/11 (0.00%) 
Eye pruritus  1  0/15 (0.00%)  1/11 (9.09%) 
Eye swelling  1  2/15 (13.33%)  0/11 (0.00%) 
Eyelid oedema  1  0/15 (0.00%)  1/11 (9.09%) 
Lacrimation increased  1  1/15 (6.67%)  0/11 (0.00%) 
Ocular discomfort  1  1/15 (6.67%)  0/11 (0.00%) 
Photophobia  1  0/15 (0.00%)  1/11 (9.09%) 
Vision blurred  1  1/15 (6.67%)  0/11 (0.00%) 
Visual acuity reduced  1  0/15 (0.00%)  1/11 (9.09%) 
Gastrointestinal disorders     
Abdominal distension  1  2/15 (13.33%)  0/11 (0.00%) 
Abdominal pain  1  2/15 (13.33%)  1/11 (9.09%) 
Abdominal pain upper  1  1/15 (6.67%)  0/11 (0.00%) 
Constipation  1  2/15 (13.33%)  4/11 (36.36%) 
Diarrhoea  1  7/15 (46.67%)  5/11 (45.45%) 
Dry mouth  1  2/15 (13.33%)  0/11 (0.00%) 
Dyspepsia  1  1/15 (6.67%)  1/11 (9.09%) 
Dysphagia  1  1/15 (6.67%)  0/11 (0.00%) 
Flatulence  1  1/15 (6.67%)  0/11 (0.00%) 
Gastrooesophageal reflux disease  1  1/15 (6.67%)  0/11 (0.00%) 
Lip swelling  1  1/15 (6.67%)  0/11 (0.00%) 
Mouth swelling  1  1/15 (6.67%)  0/11 (0.00%) 
Nausea  1  10/15 (66.67%)  6/11 (54.55%) 
Retching  1  1/15 (6.67%)  0/11 (0.00%) 
Tooth disorder  1  1/15 (6.67%)  0/11 (0.00%) 
Vomiting  1  3/15 (20.00%)  4/11 (36.36%) 
General disorders     
Application site reaction  1  1/15 (6.67%)  0/11 (0.00%) 
Catheter site inflammation  1  0/15 (0.00%)  1/11 (9.09%) 
Chest discomfort  1  2/15 (13.33%)  1/11 (9.09%) 
Chest pain  1  2/15 (13.33%)  0/11 (0.00%) 
Chills  1  3/15 (20.00%)  1/11 (9.09%) 
Fatigue  1  8/15 (53.33%)  5/11 (45.45%) 
General physical health deterioration  1  2/15 (13.33%)  0/11 (0.00%) 
Influenza like illness  1  1/15 (6.67%)  0/11 (0.00%) 
Infusion site erythema  1  1/15 (6.67%)  0/11 (0.00%) 
Infusion site pain  1  2/15 (13.33%)  0/11 (0.00%) 
Injury associated with device  1  1/15 (6.67%)  0/11 (0.00%) 
Non-cardiac chest pain  1  1/15 (6.67%)  0/11 (0.00%) 
Oedema  1  1/15 (6.67%)  0/11 (0.00%) 
Oedema peripheral  1  1/15 (6.67%)  0/11 (0.00%) 
Pain  1  0/15 (0.00%)  2/11 (18.18%) 
Pyrexia  1  8/15 (53.33%)  2/11 (18.18%) 
Sluggishness  1  1/15 (6.67%)  0/11 (0.00%) 
Hepatobiliary disorders     
Cholangitis  1  1/15 (6.67%)  0/11 (0.00%) 
Infections and infestations     
Bacteraemia  1  1/15 (6.67%)  0/11 (0.00%) 
Candida infection  1  1/15 (6.67%)  0/11 (0.00%) 
Catheter site infection  1  0/15 (0.00%)  2/11 (18.18%) 
Clostridium difficile infection  1  0/15 (0.00%)  1/11 (9.09%) 
Conjunctivitis  1  1/15 (6.67%)  0/11 (0.00%) 
Ear infection  1  1/15 (6.67%)  0/11 (0.00%) 
Infection  1  1/15 (6.67%)  0/11 (0.00%) 
Influenza  1  1/15 (6.67%)  0/11 (0.00%) 
Nasopharyngitis  1  3/15 (20.00%)  0/11 (0.00%) 
Respiratory tract infection  1  3/15 (20.00%)  0/11 (0.00%) 
Upper respiratory tract infection  1  2/15 (13.33%)  1/11 (9.09%) 
Urinary tract infection  1  3/15 (20.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications     
Humerus fracture  1  0/15 (0.00%)  1/11 (9.09%) 
Procedural nausea  1  1/15 (6.67%)  0/11 (0.00%) 
Radiation skin injury  1  1/15 (6.67%)  0/11 (0.00%) 
Skin abrasion  1  1/15 (6.67%)  0/11 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  1/15 (6.67%)  2/11 (18.18%) 
Aspartate aminotransferase increased  1  0/15 (0.00%)  1/11 (9.09%) 
Blood alkaline phosphatase increased  1  0/15 (0.00%)  1/11 (9.09%) 
Blood calcium decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Blood calcium increased  1  0/15 (0.00%)  1/11 (9.09%) 
Blood uric acid increased  1  1/15 (6.67%)  0/11 (0.00%) 
Carbon dioxide decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Eosinophil count increased  1  0/15 (0.00%)  1/11 (9.09%) 
Haemoglobin decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Lymphocyte count decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Monocyte count decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Monocyte count increased  1  0/15 (0.00%)  1/11 (9.09%) 
Neutrophil count increased  1  0/15 (0.00%)  1/11 (9.09%) 
Olfactory test abnormal  1  1/15 (6.67%)  0/11 (0.00%) 
Platelet count decreased  1  1/15 (6.67%)  1/11 (9.09%) 
Protein total decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Red blood cell count decreased  1  0/15 (0.00%)  1/11 (9.09%) 
Troponin increased  1  1/15 (6.67%)  0/11 (0.00%) 
Weight decreased  1  1/15 (6.67%)  0/11 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/15 (20.00%)  0/11 (0.00%) 
Dehydration  1  1/15 (6.67%)  0/11 (0.00%) 
Fluid retention  1  1/15 (6.67%)  0/11 (0.00%) 
Hyperglycaemia  1  0/15 (0.00%)  1/11 (9.09%) 
Hyperkalaemia  1  0/15 (0.00%)  1/11 (9.09%) 
Hypocalcaemia  1  0/15 (0.00%)  1/11 (9.09%) 
Hypokalaemia  1  2/15 (13.33%)  3/11 (27.27%) 
Hypomagnesaemia  1  1/15 (6.67%)  1/11 (9.09%) 
Hyponatraemia  1  1/15 (6.67%)  0/11 (0.00%) 
Hypophosphataemia  1  0/15 (0.00%)  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/15 (6.67%)  1/11 (9.09%) 
Arthritis  1  1/15 (6.67%)  0/11 (0.00%) 
Back pain  1  2/15 (13.33%)  1/11 (9.09%) 
Bone pain  1  2/15 (13.33%)  0/11 (0.00%) 
Diastasis recti abdominis  1  1/15 (6.67%)  0/11 (0.00%) 
Joint swelling  1  1/15 (6.67%)  0/11 (0.00%) 
Limb discomfort  1  1/15 (6.67%)  0/11 (0.00%) 
Muscle spasms  1  1/15 (6.67%)  1/11 (9.09%) 
Muscular weakness  1  2/15 (13.33%)  0/11 (0.00%) 
Musculoskeletal chest pain  1  3/15 (20.00%)  0/11 (0.00%) 
Musculoskeletal discomfort  1  0/15 (0.00%)  1/11 (9.09%) 
Musculoskeletal pain  1  2/15 (13.33%)  0/11 (0.00%) 
Neck pain  1  0/15 (0.00%)  1/11 (9.09%) 
Pain in extremity  1  1/15 (6.67%)  2/11 (18.18%) 
Soft tissue mass  1  1/15 (6.67%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastrointestinal neoplasm  1  1/15 (6.67%)  0/11 (0.00%) 
Plasmacytoma  1  1/15 (6.67%)  0/11 (0.00%) 
Nervous system disorders     
Areflexia  1  0/15 (0.00%)  1/11 (9.09%) 
Dizziness  1  2/15 (13.33%)  1/11 (9.09%) 
Dysgeusia  1  1/15 (6.67%)  0/11 (0.00%) 
Headache  1  5/15 (33.33%)  3/11 (27.27%) 
Lethargy  1  1/15 (6.67%)  1/11 (9.09%) 
Migraine  1  0/15 (0.00%)  1/11 (9.09%) 
Neuropathy peripheral  1  1/15 (6.67%)  1/11 (9.09%) 
Restless legs syndrome  1  0/15 (0.00%)  1/11 (9.09%) 
Sciatica  1  1/15 (6.67%)  0/11 (0.00%) 
Somnolence  1  1/15 (6.67%)  0/11 (0.00%) 
Syncope  1  0/15 (0.00%)  1/11 (9.09%) 
Psychiatric disorders     
Confusional state  1  3/15 (20.00%)  0/11 (0.00%) 
Depression  1  0/15 (0.00%)  2/11 (18.18%) 
Insomnia  1  3/15 (20.00%)  1/11 (9.09%) 
Mood altered  1  1/15 (6.67%)  0/11 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/15 (6.67%)  0/11 (0.00%) 
Dysuria  1  2/15 (13.33%)  0/11 (0.00%) 
Micturition urgency  1  1/15 (6.67%)  0/11 (0.00%) 
Pollakiuria  1  1/15 (6.67%)  0/11 (0.00%) 
Renal failure  1  0/15 (0.00%)  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  6/15 (40.00%)  3/11 (27.27%) 
Dysphonia  1  1/15 (6.67%)  0/11 (0.00%) 
Dyspnoea  1  7/15 (46.67%)  1/11 (9.09%) 
Dyspnoea exertional  1  1/15 (6.67%)  0/11 (0.00%) 
Dyspnoea paroxysmal nocturnal  1  0/15 (0.00%)  1/11 (9.09%) 
Epistaxis  1  4/15 (26.67%)  1/11 (9.09%) 
Hypoxia  1  1/15 (6.67%)  1/11 (9.09%) 
Oropharyngeal pain  1  1/15 (6.67%)  0/11 (0.00%) 
Oropharyngeal plaque  1  1/15 (6.67%)  0/11 (0.00%) 
Pleural effusion  1  1/15 (6.67%)  0/11 (0.00%) 
Productive cough  1  2/15 (13.33%)  1/11 (9.09%) 
Pulmonary hypertension  1  1/15 (6.67%)  0/11 (0.00%) 
Sinus congestion  1  1/15 (6.67%)  0/11 (0.00%) 
Tachypnoea  1  1/15 (6.67%)  0/11 (0.00%) 
Throat irritation  1  1/15 (6.67%)  0/11 (0.00%) 
Wheezing  1  2/15 (13.33%)  1/11 (9.09%) 
Skin and subcutaneous tissue disorders     
Acne  1  1/15 (6.67%)  0/11 (0.00%) 
Angioedema  1  1/15 (6.67%)  0/11 (0.00%) 
Erythema  1  2/15 (13.33%)  0/11 (0.00%) 
Hyperhidrosis  1  1/15 (6.67%)  1/11 (9.09%) 
Hyperkeratosis  1  0/15 (0.00%)  1/11 (9.09%) 
Pruritus  1  0/15 (0.00%)  1/11 (9.09%) 
Rash  1  2/15 (13.33%)  0/11 (0.00%) 
Rash erythematous  1  0/15 (0.00%)  1/11 (9.09%) 
Swelling face  1  1/15 (6.67%)  0/11 (0.00%) 
Vascular disorders     
Flushing  1  2/15 (13.33%)  1/11 (9.09%) 
Hypertension  1  3/15 (20.00%)  1/11 (9.09%) 
Hypotension  1  2/15 (13.33%)  2/11 (18.18%) 
Peripheral coldness  1  1/15 (6.67%)  0/11 (0.00%) 
Venous thrombosis  1  1/15 (6.67%)  0/11 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01949532     History of Changes
Other Study ID Numbers: CFZ001
20130401 ( Other Identifier: Sponsor )
First Submitted: September 6, 2013
First Posted: September 24, 2013
Results First Submitted: March 31, 2016
Results First Posted: May 4, 2016
Last Update Posted: May 2, 2017