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

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00721734
• Collaborator: (none)
• Enrollment: 50
• Locations: 5
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the influence of renal impairment on carfilzomib in patients with Multiple Myeloma (MM).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Renal Insufficiency	Drug: Carfilzomib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of the Safety and Pharmacokinetics of Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carfilzomib Carfilzomib, 15 mg/m², was 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.	Drug: Carfilzomib; Carfilzomib was administered intravenously (IV) at a rate of approximately 10 mL/minute.; Other Names: PR-171 Kyprolis®

Outcome Measures

Primary Outcome Measures

1. Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 [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.]

   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.

Secondary Outcome Measures

1. Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 [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.]

2. Clearance (CL) of Carfilzomib on Day 15 of Cycle 2 [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.]

3. Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 [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.]

4. Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 [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.]

5. Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2 [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.]

6. Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 [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.]

7. Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 [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.]

8. Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2 [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.]

9. Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 [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.]

10. Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 [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.]

11. Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2 [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.]

12. Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1 [Cycle 1, Day 1, 0-5 and 5-24 hours post-dose]

    The percentage of carfilzomib excreted in urine was calculated as the total amount excreted over 24 hours/dose.

13. Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1 [Cycle 1, Day 15, 0-5 and 5-24 hours post-dose]

    The percentage of carfilzomib excreted in urine was calculated as the total amount excreted over 24 hours/dose.

14. Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 [Cycle 1, Day 1, 0-5 and 5-24 hours post-dose]

    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.

15. Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 [Cycle 1, Day 15, 0-5 and 5-24 hours post-dose]

    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.

16. Plasma Protein Binding (PPB) of Carfilzomib [End of injection and 5 minutes post-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 15]

    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).

17. Overall Response Rate (ORR) [From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.]

    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.

18. Clinical Benefit Rate (CBR) [From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.]

    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.

19. Duration of Response [Participants were followed for disease progression for up to 2 years.]

    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.

20. Time to Progression (TTP) [Participants were followed for disease progression for up to 2 years.]

    Time to Progression is defined as the time from first dose of carfilzomib to disease progression. Median TTP was estimated using Kaplan-Meier methods.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines

2. Males and females ≥ 18 years of age

3. Multiple Myeloma

4. Documented relapsed or progressive disease (PD) after receiving at least two prior treatment regimens (induction therapy with autologous stem cell transplant and maintenance is considered a single regimen), and must have achieved a minimal response or better to at least one of the regimens

5. Current measurable disease, as indicated by one or more of the following:

• Serum M-protein ≥ 0.5 g/dL

• Urine M-protein ≥ 200 mg/24 hours

• Serum Free Light Chain (FLC) assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal

1. Life expectancy of more than three months

2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

3. Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN

4. Total white blood cell (WBC) count ≥ 2,000/mm³

5. Absolute neutrophil count (ANC) ≥ 1,000/mm³

6. Hemoglobin ≥ 7 gm/dL

• Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines

1. Platelet count ≥ 30,000/ mm³

2. Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test

3. Male subjects must use an effective barrier method of contraception during study and for three months following the last dose if sexually active with a female of child-bearing potential

Exclusion Criteria:

1. Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days prior to first dose of study drug

2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

3. Plasma cell leukemia

4. Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 14 days prior to first dose of study drug or antibody therapy within 6 weeks prior to first dose of study drug

5. Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose

6. Participation in an investigational therapeutic study within 14 days prior to first dose of study drug

7. Prior carfilzomib treatment

8. Pregnant or lactating females

9. Major surgery within 3 weeks prior to first dose of study drug

10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities or myocardial infarction in the three months prior to first dose of study drug

11. Uncontrolled hypertension

12. Recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose of study drug

13. Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity

14. Active hepatitis A, B, or C infection

15. Other malignancy within the past 3 years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer < Gleason Grade 7 with stable prostate specific antigen (PSA) levels

16. Any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

17. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days prior to enrollment

18. Subjects in whom the required program of oral hydration and intravenous fluid hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac impairment

19. Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis

20. Subjects with a known contraindication to receiving dexamethasone or allopurinol

21. Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF and GM-CSF) within 1 week prior to first dose of study drug

22. Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug

23. RBC and platelet transfusions within 7 days prior to first dose of study drug

24. Subjects with known or suspected cardiac amyloidosis

25. Subjects with myelodysplastic syndrome

26. Subjects undergoing peritoneal dialysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California- San Francisco	San Francisco	California	United States	94143
2	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Cornell University	New York	New York	United States	10021

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00721734
• Other Study ID Numbers: PX-171-005
• First Posted: Jul 24, 2008
• Last Update Posted: May 2, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Amgen: Myeloma; Renal Insufficiency; Proteasome; Hematological; carfilzomib; PR-171
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Renal Insufficiency

Study Results

Participant Flow

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.

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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	0	2	2	2
NOT COMPLETED	8	12	8	6	6

Baseline Characteristics

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis	Total
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 Participants	12	12	10	8	8	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 50%	8 66.7%	4 40%	1 12.5%	7 87.5%	26 52%
>=65 years	6 50%	4 33.3%	6 60%	7 87.5%	1 12.5%	24 48%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	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 (Count of Participants)
Female	4 33.3%	8 66.7%	3 30%	3 37.5%	4 50%	22 44%
Male	8 66.7%	4 33.3%	7 70%	5 62.5%	4 50%	28 56%
Race/Ethnicity, Customized (participants) [Number]
African American	2 16.7%	2 16.7%	4 40%	1 12.5%	2 25%	11 22%
Asian/Pacific Islander	0 0%	2 16.7%	0 0%	0 0%	1 12.5%	3 6%
Caucasian	10 83.3%	8 66.7%	6 60%	7 87.5%	5 62.5%	36 72%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0 (Fully active)	4 33.3%	2 16.7%	0 0%	2 25%	0 0%	8 16%
1 (Restrictive but ambulatory)	8 66.7%	9 75%	9 90%	1 12.5%	5 62.5%	32 64%
2 (Ambulatory but unable to work)	0 0%	1 8.3%	1 10%	5 62.5%	3 37.5%	10 20%

Outcome Measures

1. Primary Outcome

Title	Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
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.

Outcome Measure Data

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
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.
Measure Participants	6	6	3	4	5
Mean (Standard Deviation) [liters/hour]	151 (79.3)	113 (40.7)	288 (264)	170 (58.4)	170 (60.2)

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
Statistical Test of Hypothesis	p-Value	0.4114
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.607
	Confidence Interval	(2-Sided) 95%; -2.129 to 0.914
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Clearance (CL) of Carfilzomib on Day 15 of Cycle 1
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.

Outcome Measure Data

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
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.
Measure Participants	5	5	3	1	5
Mean (Standard Deviation) [liters/hour]	660 (1134)	115 (34.7)	119 (16.5)	110 (NA)	114 (61.2)

3. Secondary Outcome

Title	Clearance (CL) of Carfilzomib on Day 15 of Cycle 2
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.

Outcome Measure Data

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
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.
Measure Participants	0	0	1	1	0
Mean (Standard Deviation) [liters/hour]	679 (NA)	46.6 (NA)

4. Secondary Outcome

Title	Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1
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.

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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.
Measure Participants	8	9	5	5	8
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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
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.
Measure Participants	7	8	5	4	6
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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
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.
Measure Participants	0	0	1	2	0
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	244 (NA)	3064 (3.9)

7. Secondary Outcome

Title	Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1
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.

Outcome Measure Data

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
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.
Measure Participants	6	6	3	4	5
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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
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.
Measure Participants	5	5	3	1	5
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	127 (240)	236 (44.3)	257 (10.9)	218 (NA)	272 (46.4)

9. Secondary Outcome

Title	Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2
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.

Outcome Measure Data

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
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.
Measure Participants	0	0	1	1	0
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	48.6 (NA)	579 (NA)

10. Secondary Outcome

Title	Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1
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.

Outcome Measure Data

Analysis Population Description

PK evaluable population

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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.
Measure Participants	8	9	5	5	8
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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
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.
Measure Participants	7	8	5	4	6
Geometric Mean (Geometric Coefficient of Variation) [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
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.

Outcome Measure Data

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
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.
Measure Participants	0	0	1	2	0
Geometric Mean (Geometric Coefficient of Variation) [hr*ng/mL]	47.3 (NA)	345 (83.6)

13. Secondary Outcome

Title	Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1
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

Outcome Measure Data

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
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.
Measure Participants	8	8	7	5	0
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	7	6	5	4	0
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
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.
Measure Participants	8	9	7	5	0
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
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

Outcome Measure Data

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
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.
Measure Participants	7	6	5	4	0
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
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

Outcome Measure Data

Analysis Population Description

Participants with available data

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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.
Measure Participants	11	8	9	9	7
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)
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.

Outcome Measure Data

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
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.
Measure Participants	11	11	9	8	8
Number (95% Confidence Interval) [percentage of participants]	18.2 151.7%	27.3 227.5%	22.2 222%	25.0 312.5%	37.5 468.8%

19. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
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.

Outcome Measure Data

Analysis Population Description

The response evaluable population

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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.
Measure Participants	11	11	9	8	8
Number (95% Confidence Interval) [percentage of participants]	27.3 227.5%	36.4 303.3%	22.2 222%	37.5 468.8%	37.5 468.8%

20. Secondary Outcome

Title	Duration of Response
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.

Outcome Measure Data

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
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.
Measure Participants	2	3	2	2	3
Median (95% Confidence Interval) [months]	NA	NA	14.8	NA	7.9

21. Secondary Outcome

Title	Time to Progression (TTP)
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.

Outcome Measure Data

Analysis Population Description

Response Evaluable Population

Arm/Group Title	Carfilzomib - Normal RF	Carfilzomib - Mild RI	Carfilzomib - Moderate RI	Carfilzomib - Severe RI	Carfilzomib - Dialysis
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.
Measure Participants	11	11	9	8	8
Median (95% Confidence Interval) [months]	4.4	5.6	2.8	9.6	6.5

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Carfilzomib - Normal RF		Carfilzomib - Mild RI		Carfilzomib - Moderate RI		Carfilzomib - Severe RI		Carfilzomib - Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		8/12 (66.7%)		10/10 (100%)		6/8 (75%)		8/8 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Cardiac disorders
Angina pectoris	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Angina unstable	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Atrial fibrillation	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Atrial flutter	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Cardiac failure congestive	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		2/8 (25%)		0/8 (0%)
Right ventricular failure	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Diarrhoea	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Hiatus hernia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Nausea	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Small intestinal obstruction	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Vomiting	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
General disorders
Disease progression	0/12 (0%)		3/12 (25%)		0/10 (0%)		1/8 (12.5%)		3/8 (37.5%)
Non-cardiac chest pain	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Oedema peripheral	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pyrexia	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Hepatobiliary disorders
Venoocclusive liver disease	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Immune system disorders
Amyloidosis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Infections and infestations
Bronchitis	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Bronchitis viral	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Cellulitis	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Central line infection	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Gastroenteritis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Influenza	0/12 (0%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		1/8 (12.5%)
Injection site cellulitis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Paronychia	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pneumonia	2/12 (16.7%)		2/12 (16.7%)		4/10 (40%)		2/8 (25%)		0/8 (0%)
Pneumonia bacterial	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Respiratory tract infection bacterial	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Sepsis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Septic shock	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Streptococcal bacteraemia	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Upper respiratory tract infection	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Urinary tract infection	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		1/8 (12.5%)
Urosepsis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Investigations
Blood alkaline phosphatase increased	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood creatinine increased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Metabolism and nutrition disorders
Dehydration	0/12 (0%)		0/12 (0%)		2/10 (20%)		2/8 (25%)		0/8 (0%)
Hypercalcaemia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypophosphataemia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Pathological fracture	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Nervous system disorders
Headache	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Spinal cord compression	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Syncope	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Psychiatric disorders
Depression	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Mental status changes	0/12 (0%)		1/12 (8.3%)		3/10 (30%)		0/8 (0%)		0/8 (0%)
Renal and urinary disorders
Renal failure	0/12 (0%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		0/8 (0%)
Renal failure acute	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		2/8 (25%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Chronic obstructive pulmonary disease	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Dyspnoea	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Pleural effusion	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Pneumonia aspiration	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Pulmonary embolism	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pulmonary hypertension	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Respiratory alkalosis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Respiratory failure	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		2/8 (25%)
Vascular disorders
Deep vein thrombosis	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Superior vena caval occlusion	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Carfilzomib - Normal RF		Carfilzomib - Mild RI		Carfilzomib - Moderate RI		Carfilzomib - Severe RI		Carfilzomib - Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		12/12 (100%)		10/10 (100%)		8/8 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Anaemia	6/12 (50%)		7/12 (58.3%)		7/10 (70%)		5/8 (62.5%)		5/8 (62.5%)
Hypocoagulable state	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Leukopenia	1/12 (8.3%)		1/12 (8.3%)		2/10 (20%)		0/8 (0%)		1/8 (12.5%)
Lymphadenopathy	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Lymphopenia	4/12 (33.3%)		4/12 (33.3%)		2/10 (20%)		2/8 (25%)		4/8 (50%)
Neutropenia	2/12 (16.7%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Thrombocytopenia	4/12 (33.3%)		6/12 (50%)		5/10 (50%)		3/8 (37.5%)		5/8 (62.5%)
Cardiac disorders
Angina pectoris	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Arrhythmia	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Atrial fibrillation	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		2/8 (25%)
Bradycardia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Cardiac failure acute	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Cardiac failure congestive	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Dilatation atrial	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Tachycardia	0/12 (0%)		0/12 (0%)		2/10 (20%)		2/8 (25%)		1/8 (12.5%)
Ear and labyrinth disorders
Ear congestion	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Vertigo positional	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Eye disorders
Conjunctivitis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Diplopia	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Dry eye	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Eye pain	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Keratitis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Abdominal distension	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Abdominal pain	1/12 (8.3%)		2/12 (16.7%)		2/10 (20%)		0/8 (0%)		4/8 (50%)
Abdominal pain upper	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Bowel sounds abnormal	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Colitis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Colonic haemorrhage	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Colonic polyp	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Constipation	3/12 (25%)		6/12 (50%)		5/10 (50%)		2/8 (25%)		3/8 (37.5%)
Diarrhoea	5/12 (41.7%)		6/12 (50%)		5/10 (50%)		2/8 (25%)		4/8 (50%)
Dry mouth	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Dyspepsia	1/12 (8.3%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		0/8 (0%)
Flatulence	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Gastrooesophageal reflux disease	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Haemorrhoids	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Hypoaesthesia oral	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Impaired gastric emptying	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Inguinal hernia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Mouth haemorrhage	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Mouth ulceration	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Nausea	6/12 (50%)		4/12 (33.3%)		6/10 (60%)		1/8 (12.5%)		4/8 (50%)
Oral pain	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Toothache	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Vomiting	2/12 (16.7%)		1/12 (8.3%)		3/10 (30%)		0/8 (0%)		3/8 (37.5%)
General disorders
Asthenia	1/12 (8.3%)		1/12 (8.3%)		3/10 (30%)		2/8 (25%)		2/8 (25%)
Catheter site haematoma	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Catheter site inflammation	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Catheter site related reaction	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Chest discomfort	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Chest pain	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Chills	1/12 (8.3%)		2/12 (16.7%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Disease progression	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		2/8 (25%)		0/8 (0%)
Face oedema	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Facial pain	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Fatigue	9/12 (75%)		9/12 (75%)		6/10 (60%)		4/8 (50%)		4/8 (50%)
Generalised oedema	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypothermia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Infusion related reaction	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Infusion site pain	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		1/8 (12.5%)
Local swelling	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Mass	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Mucosal inflammation	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Non-cardiac chest pain	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Oedema	2/12 (16.7%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Oedema peripheral	4/12 (33.3%)		2/12 (16.7%)		3/10 (30%)		3/8 (37.5%)		1/8 (12.5%)
Pain	0/12 (0%)		3/12 (25%)		4/10 (40%)		0/8 (0%)		4/8 (50%)
Pitting oedema	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Pyrexia	3/12 (25%)		2/12 (16.7%)		3/10 (30%)		0/8 (0%)		4/8 (50%)
Tenderness	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Immune system disorders
Seasonal allergy	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Infections and infestations
Bacteraemia	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Cellulitis	2/12 (16.7%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Herpes simplex	2/12 (16.7%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Herpes zoster	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Influenza	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Nasopharyngitis	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Oral candidiasis	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Paronychia	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pneumonia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Pseudomonas infection	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Respiratory syncytial virus infection	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Rhinitis	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Sepsis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		3/8 (37.5%)
Sinusitis	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Staphylococcal infection	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Tinea pedis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Upper respiratory tract infection	2/12 (16.7%)		1/12 (8.3%)		1/10 (10%)		3/8 (37.5%)		2/8 (25%)
Urinary tract infection	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Urinary tract infection pseudomonal	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Injury, poisoning and procedural complications
Arthropod bite	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Contusion	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Limb injury	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Post procedural haemorrhage	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Post procedural vomiting	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Postoperative fever	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Procedural pain	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Skin injury	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Investigations
Abdominal bruit	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Activated partial thromboplastin time prolonged	0/12 (0%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		2/8 (25%)
Alanine aminotransferase increased	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Aspartate aminotransferase increased	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Blood albumin decreased	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Blood alkaline phosphatase increased	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood calcium increased	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood creatinine decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Blood creatinine increased	1/12 (8.3%)		2/12 (16.7%)		5/10 (50%)		1/8 (12.5%)		2/8 (25%)
Blood glucose decreased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Blood glucose increased	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood magnesium decreased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Blood phosphorus decreased	1/12 (8.3%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		1/8 (12.5%)
Blood phosphorus increased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Blood potassium decreased	3/12 (25%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		2/8 (25%)
Blood potassium increased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Blood pressure diastolic decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Blood pressure increased	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood sodium decreased	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood uric acid increased	0/12 (0%)		2/12 (16.7%)		3/10 (30%)		1/8 (12.5%)		3/8 (37.5%)
Breath sounds abnormal	0/12 (0%)		2/12 (16.7%)		3/10 (30%)		1/8 (12.5%)		0/8 (0%)
Carbon dioxide decreased	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Cardiac murmur	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Ejection fraction decreased	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Haemoglobin decreased	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		1/8 (12.5%)
International normalised ratio increased	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Lymphocyte count decreased	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Occult blood positive	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Platelet count decreased	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Respiratory rate decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Troponin increased	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Urine output decreased	0/12 (0%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		0/8 (0%)
Weight decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
White blood cell count decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Metabolism and nutrition disorders
Acidosis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Anorexia	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Decreased appetite	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Dehydration	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypercalcaemia	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Hyperglycaemia	3/12 (25%)		1/12 (8.3%)		2/10 (20%)		2/8 (25%)		2/8 (25%)
Hyperkalaemia	0/12 (0%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		2/8 (25%)
Hypermagnesaemia	0/12 (0%)		0/12 (0%)		1/10 (10%)		1/8 (12.5%)		0/8 (0%)
Hypernatraemia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hyperphosphataemia	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		2/8 (25%)
Hyperuricaemia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypoalbuminaemia	1/12 (8.3%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypocalcaemia	0/12 (0%)		0/12 (0%)		2/10 (20%)		1/8 (12.5%)		2/8 (25%)
Hypoglycaemia	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		1/8 (12.5%)		2/8 (25%)
Hypokalaemia	5/12 (41.7%)		3/12 (25%)		4/10 (40%)		2/8 (25%)		4/8 (50%)
Hypomagnesaemia	3/12 (25%)		4/12 (33.3%)		4/10 (40%)		2/8 (25%)		3/8 (37.5%)
Hyponatraemia	0/12 (0%)		0/12 (0%)		2/10 (20%)		1/8 (12.5%)		0/8 (0%)
Hypophosphataemia	1/12 (8.3%)		1/12 (8.3%)		2/10 (20%)		0/8 (0%)		1/8 (12.5%)
Lactic acidosis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Overweight	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)		1/12 (8.3%)		4/10 (40%)		0/8 (0%)		0/8 (0%)
Back pain	5/12 (41.7%)		3/12 (25%)		1/10 (10%)		1/8 (12.5%)		2/8 (25%)
Bone pain	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		1/8 (12.5%)
Chest wall pain	3/12 (25%)		1/12 (8.3%)		2/10 (20%)		2/8 (25%)		1/8 (12.5%)
Joint range of motion decreased	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Joint swelling	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Muscle spasms	3/12 (25%)		2/12 (16.7%)		1/10 (10%)		1/8 (12.5%)		2/8 (25%)
Muscular weakness	0/12 (0%)		2/12 (16.7%)		2/10 (20%)		1/8 (12.5%)		2/8 (25%)
Myalgia	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Neck pain	1/12 (8.3%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Nodule on extremity	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Pain in extremity	5/12 (41.7%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		2/8 (25%)
Pain in jaw	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pathological fracture	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		3/8 (37.5%)
Rotator cuff syndrome	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Sensation of heaviness	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Shoulder pain	2/12 (16.7%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Nervous system disorders
Aphasia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Areflexia	1/12 (8.3%)		2/12 (16.7%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Balance disorder	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Depressed level of consciousness	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Diplegia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Disturbance in attention	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Dizziness	2/12 (16.7%)		2/12 (16.7%)		2/10 (20%)		1/8 (12.5%)		1/8 (12.5%)
Dysgeusia	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Headache	5/12 (41.7%)		2/12 (16.7%)		2/10 (20%)		0/8 (0%)		2/8 (25%)
Hypoaesthesia	2/12 (16.7%)		3/12 (25%)		1/10 (10%)		2/8 (25%)		1/8 (12.5%)
Hyporeflexia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Lethargy	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Neuropathic pain	3/12 (25%)		4/12 (33.3%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Neuropathy	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		1/8 (12.5%)
Neuropathy peripheral	2/12 (16.7%)		1/12 (8.3%)		2/10 (20%)		2/8 (25%)		0/8 (0%)
Paraesthesia	2/12 (16.7%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Post herpetic neuralgia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Sinus headache	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Somnolence	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Spinal cord compression	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Syncope	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Psychiatric disorders
Anxiety	1/12 (8.3%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Delirium	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Depression	2/12 (16.7%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		2/8 (25%)
Insomnia	3/12 (25%)		1/12 (8.3%)		2/10 (20%)		2/8 (25%)		0/8 (0%)
Mental status changes	0/12 (0%)		1/12 (8.3%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Mood altered	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Renal and urinary disorders
Azotaemia	0/12 (0%)		0/12 (0%)		0/10 (0%)		2/8 (25%)		0/8 (0%)
Incontinence	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Nephrolithiasis	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Nocturia	0/12 (0%)		0/12 (0%)		0/10 (0%)		2/8 (25%)		0/8 (0%)
Pollakiuria	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Renal failure	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Renal failure chronic	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Renal impairment	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Urinary tract pain	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Urine flow decreased	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Reproductive system and breast disorders
Erectile dysfunction	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Cough	2/12 (16.7%)		2/12 (16.7%)		4/10 (40%)		1/8 (12.5%)		1/8 (12.5%)
Dyspnoea	6/12 (50%)		3/12 (25%)		4/10 (40%)		3/8 (37.5%)		3/8 (37.5%)
Dyspnoea exacerbated	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Dyspnoea exertional	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Epistaxis	1/12 (8.3%)		1/12 (8.3%)		2/10 (20%)		0/8 (0%)		2/8 (25%)
Hiccups	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hypoxia	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Nasal congestion	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Nasal dryness	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Pharyngolaryngeal pain	2/12 (16.7%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		2/8 (25%)
Pleural effusion	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Productive cough	1/12 (8.3%)		2/12 (16.7%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Pulmonary hypertension	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Rales	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Rhinalgia	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Sinus congestion	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Sneezing	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Tachypnoea	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Throat irritation	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Wheezing	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Acne	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Alopecia	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Blood blister	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Decubitus ulcer	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Dermatitis	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Dry skin	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Ecchymosis	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Erythema	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Hyperhidrosis	0/12 (0%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Night sweats	1/12 (8.3%)		0/12 (0%)		2/10 (20%)		0/8 (0%)		0/8 (0%)
Petechiae	1/12 (8.3%)		2/12 (16.7%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Pruritus	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		1/8 (12.5%)
Rash	1/12 (8.3%)		0/12 (0%)		2/10 (20%)		1/8 (12.5%)		0/8 (0%)
Rash macular	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Rash pruritic	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Skin exfoliation	0/12 (0%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Skin lesion	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Skin tightness	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Swelling face	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)
Vascular disorders
Deep vein thrombosis	1/12 (8.3%)		0/12 (0%)		1/10 (10%)		0/8 (0%)		0/8 (0%)
Haematoma	0/12 (0%)		0/12 (0%)		0/10 (0%)		1/8 (12.5%)		0/8 (0%)
Hypertension	1/12 (8.3%)		0/12 (0%)		2/10 (20%)		1/8 (12.5%)		2/8 (25%)
Hypotension	0/12 (0%)		1/12 (8.3%)		0/10 (0%)		0/8 (0%)		4/8 (50%)
Pallor	1/12 (8.3%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Superior vena caval occlusion	0/12 (0%)		0/12 (0%)		0/10 (0%)		0/8 (0%)		1/8 (12.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.