Multiple Myeloma, Renal Insufficiency
Conditions
Keywords
Myeloma, Renal Insufficiency, Proteasome, Hematological, carfilzomib, PR-171
Brief summary
The purpose of this study is to assess the influence of renal impairment on carfilzomib in patients with Multiple Myeloma (MM).
Interventions
DRUGCarfilzomib
Carfilzomib was administered intravenously (IV) at a rate of approximately 10 mL/minute.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 6. Life expectancy of more than three months 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 8. Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) \< 3 times ULN 9. Total white blood cell (WBC) count ≥ 2,000/mm³ 10. Absolute neutrophil count (ANC) ≥ 1,000/mm³ 11. Hemoglobin ≥ 7 gm/dL * Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines 12. Platelet count ≥ 30,000/ mm³ 13. 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 14. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. | — |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Carfilzomib - Normal RF 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. | 12 |
| Carfilzomib - Mild RI 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. | 12 |
| Carfilzomib - Moderate RI 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. | 10 |
| Carfilzomib - Severe RI 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. | 8 |
| Carfilzomib - Dialysis 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. | 8 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 4 | 0 | 3 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 3 | 10 | 4 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Carfilzomib - Normal RF | Carfilzomib - Mild RI | Carfilzomib - Moderate RI | Carfilzomib - Severe RI | Carfilzomib - Dialysis | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 6 Participants | 7 Participants | 1 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 4 Participants | 1 Participants | 7 Participants | 26 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 5.7 | 63.5 years STANDARD_DEVIATION 7.85 | 66.2 years STANDARD_DEVIATION 9.65 | 73.0 years STANDARD_DEVIATION 8.23 | 56.0 years STANDARD_DEVIATION 7.91 | 64.6 years STANDARD_DEVIATION 9.01 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active) | 4 participants | 2 participants | 0 participants | 2 participants | 0 participants | 8 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but ambulatory) | 8 participants | 9 participants | 9 participants | 1 participants | 5 participants | 32 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work) | 0 participants | 1 participants | 1 participants | 5 participants | 3 participants | 10 participants |
| Race/Ethnicity, Customized African American | 2 participants | 2 participants | 4 participants | 1 participants | 2 participants | 11 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 0 participants | 2 participants | 0 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian | 10 participants | 8 participants | 6 participants | 7 participants | 5 participants | 36 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 3 Participants | 3 Participants | 4 Participants | 22 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 7 Participants | 5 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 12 / 12 | 10 / 10 | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 5 / 12 | 8 / 12 | 10 / 10 | 6 / 8 | 8 / 8 |
Outcome results
Primary
Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
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.
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 | 151 liters/hour | Standard Deviation 79.3 |
| Carfilzomib - Mild RI | Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 | 113 liters/hour | Standard Deviation 40.7 |
| Carfilzomib - Moderate RI | Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 | 288 liters/hour | Standard Deviation 264 |
| Carfilzomib - Severe RI | Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 | 170 liters/hour | Standard Deviation 58.4 |
| Carfilzomib - Dialysis | Clearance (CL) of Carfilzomib on Day 1 of Cycle 1 | 170 liters/hour | Standard Deviation 60.2 |
Comparison: 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).p-value: 0.411495% CI: [-2.129, 0.914]Regression, Linear
Secondary
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.
Population: PK evaluable population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 | 159 hr*ng/mL | Geometric Coefficient of Variation 186 |
| Carfilzomib - Mild RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 | 289 hr*ng/mL | Geometric Coefficient of Variation 58.5 |
| Carfilzomib - Moderate RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 | 371 hr*ng/mL | Geometric Coefficient of Variation 55.2 |
| Carfilzomib - Severe RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 | 343 hr*ng/mL | Geometric Coefficient of Variation 53.1 |
| Carfilzomib - Dialysis | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1 | 264 hr*ng/mL | Geometric Coefficient of Variation 41.7 |
Secondary
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.
Population: PK evaluable population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Moderate RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2 | 47.3 hr*ng/mL | — |
| Carfilzomib - Severe RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2 | 345 hr*ng/mL | Geometric Coefficient of Variation 83.6 |
Secondary
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.
Population: PK evaluable population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 | 187 hr*ng/mL | Geometric Coefficient of Variation 75.3 |
| Carfilzomib - Mild RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 | 194 hr*ng/mL | Geometric Coefficient of Variation 67.6 |
| Carfilzomib - Moderate RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 | 199 hr*ng/mL | Geometric Coefficient of Variation 91.3 |
| Carfilzomib - Severe RI | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 | 135 hr*ng/mL | Geometric Coefficient of Variation 65.5 |
| Carfilzomib - Dialysis | Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1 | 195 hr*ng/mL | Geometric Coefficient of Variation 65.3 |
Secondary
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.
Population: PK evaluable population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 | 127 hr*ng/mL | Geometric Coefficient of Variation 240 |
| Carfilzomib - Mild RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 | 236 hr*ng/mL | Geometric Coefficient of Variation 44.3 |
| Carfilzomib - Moderate RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 | 257 hr*ng/mL | Geometric Coefficient of Variation 10.9 |
| Carfilzomib - Severe RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 | 218 hr*ng/mL | — |
| Carfilzomib - Dialysis | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1 | 272 hr*ng/mL | Geometric Coefficient of Variation 46.4 |
Secondary
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.
Population: PK evaluable population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Carfilzomib - Moderate RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2 | 48.6 hr*ng/mL |
| Carfilzomib - Severe RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2 | 579 hr*ng/mL |
Secondary
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.
Population: PK evaluable population; AUCinf could not be estimated for 11 participants in the PK population who did not have adequate PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 | 233 hr*ng/mL | Geometric Coefficient of Variation 51.6 |
| Carfilzomib - Mild RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 | 241 hr*ng/mL | Geometric Coefficient of Variation 32.4 |
| Carfilzomib - Moderate RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 | 145 hr*ng/mL | Geometric Coefficient of Variation 111 |
| Carfilzomib - Severe RI | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 | 172 hr*ng/mL | Geometric Coefficient of Variation 35.6 |
| Carfilzomib - Dialysis | Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1 | 193 hr*ng/mL | Geometric Coefficient of Variation 55.2 |
Secondary
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.
Population: The pharmacokinetic (PK) evaluable population with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 | 660 liters/hour | Standard Deviation 1134 |
| Carfilzomib - Mild RI | Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 | 115 liters/hour | Standard Deviation 34.7 |
| Carfilzomib - Moderate RI | Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 | 119 liters/hour | Standard Deviation 16.5 |
| Carfilzomib - Severe RI | Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 | 110 liters/hour | — |
| Carfilzomib - Dialysis | Clearance (CL) of Carfilzomib on Day 15 of Cycle 1 | 114 liters/hour | Standard Deviation 61.2 |
Secondary
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.
Population: The pharmacokinetic (PK) evaluable population with available data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Carfilzomib - Moderate RI | Clearance (CL) of Carfilzomib on Day 15 of Cycle 2 | 679 liters/hour |
| Carfilzomib - Severe RI | Clearance (CL) of Carfilzomib on Day 15 of Cycle 2 | 46.6 liters/hour |
Secondary
Clinical Benefit Rate (CBR)
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.
Population: The response evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carfilzomib - Normal RF | Clinical Benefit Rate (CBR) | 27.3 percentage of participants |
| Carfilzomib - Mild RI | Clinical Benefit Rate (CBR) | 36.4 percentage of participants |
| Carfilzomib - Moderate RI | Clinical Benefit Rate (CBR) | 22.2 percentage of participants |
| Carfilzomib - Severe RI | Clinical Benefit Rate (CBR) | 37.5 percentage of participants |
| Carfilzomib - Dialysis | Clinical Benefit Rate (CBR) | 37.5 percentage of participants |
Secondary
Duration of Response
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.
Population: Response Evaluable Population with a best overall response of sCR, CR, VGPR, or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carfilzomib - Normal RF | Duration of Response | NA months |
| Carfilzomib - Mild RI | Duration of Response | NA months |
| Carfilzomib - Moderate RI | Duration of Response | 14.8 months |
| Carfilzomib - Severe RI | Duration of Response | NA months |
| Carfilzomib - Dialysis | Duration of Response | 7.9 months |
Secondary
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.
Population: PK population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 | 1768 ng/mL | Geometric Coefficient of Variation 179 |
| Carfilzomib - Mild RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 | 2406 ng/mL | Geometric Coefficient of Variation 52.3 |
| Carfilzomib - Moderate RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 | 2627 ng/mL | Geometric Coefficient of Variation 31.8 |
| Carfilzomib - Severe RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 | 1914 ng/mL | Geometric Coefficient of Variation 99.8 |
| Carfilzomib - Dialysis | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1 | 3236 ng/mL | Geometric Coefficient of Variation 34.4 |
Secondary
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.
Population: PK population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Moderate RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2 | 244 ng/mL | — |
| Carfilzomib - Severe RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2 | 3064 ng/mL | Geometric Coefficient of Variation 3.9 |
Secondary
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.
Population: PK population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 | 2077 ng/mL | Geometric Coefficient of Variation 91.4 |
| Carfilzomib - Mild RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 | 1623 ng/mL | Geometric Coefficient of Variation 161 |
| Carfilzomib - Moderate RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 | 1840 ng/mL | Geometric Coefficient of Variation 92.4 |
| Carfilzomib - Severe RI | Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 | 1231 ng/mL | Geometric Coefficient of Variation 139 |
| Carfilzomib - Dialysis | Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1 | 1539 ng/mL | Geometric Coefficient of Variation 92.7 |
Secondary
Overall Response Rate (ORR)
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.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Carfilzomib - Normal RF | Overall Response Rate (ORR) | 18.2 percentage of participants |
| Carfilzomib - Mild RI | Overall Response Rate (ORR) | 27.3 percentage of participants |
| Carfilzomib - Moderate RI | Overall Response Rate (ORR) | 22.2 percentage of participants |
| Carfilzomib - Severe RI | Overall Response Rate (ORR) | 25.0 percentage of participants |
| Carfilzomib - Dialysis | Overall Response Rate (ORR) | 37.5 percentage of participants |
Secondary
Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1
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
Population: Participants in Groups 1-4 with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1 | 0.446 percentage of carfilzomib dose | Standard Deviation 0.357 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1 | 0.428 percentage of carfilzomib dose | Standard Deviation 0.262 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1 | 0.202 percentage of carfilzomib dose | Standard Deviation 0.116 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1 | 0.168 percentage of carfilzomib dose | Standard Deviation 0.067 |
Secondary
Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1
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
Population: Participants in Groups 1-4 with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carfilzomib - Normal RF | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1 | 0.490 percentage of carfilzomib dose | Standard Deviation 0.316 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1 | 0.429 percentage of carfilzomib dose | Standard Deviation 0.271 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1 | 0.160 percentage of carfilzomib dose | Standard Deviation 0.101 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1 | 0.226 percentage of carfilzomib dose | Standard Deviation 0.0921 |
Secondary
Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1
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
Population: Participants in Groups 1-4 with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carfilzomib - Normal RF | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M14 | 30.6 percentage of carfilzomib dose | Standard Deviation 11.6 |
| Carfilzomib - Normal RF | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M15 | 1.91 percentage of carfilzomib dose | Standard Deviation 1.03 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M15 | 1.55 percentage of carfilzomib dose | Standard Deviation 0.602 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M14 | 27.0 percentage of carfilzomib dose | Standard Deviation 8.47 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M14 | 22.0 percentage of carfilzomib dose | Standard Deviation 6.89 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M15 | 0.856 percentage of carfilzomib dose | Standard Deviation 0.377 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M14 | 17.0 percentage of carfilzomib dose | Standard Deviation 4.67 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1 | M15 | 0.475 percentage of carfilzomib dose | Standard Deviation 0.249 |
Secondary
Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1
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
Population: Participants in Groups 1-4 with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carfilzomib - Normal RF | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M14 | 33.1 percentage of carfilzomib dose | Standard Deviation 13.1 |
| Carfilzomib - Normal RF | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M15 | 1.93 percentage of carfilzomib dose | Standard Deviation 1.12 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M15 | 1.42 percentage of carfilzomib dose | Standard Deviation 0.314 |
| Carfilzomib - Mild RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M14 | 25.0 percentage of carfilzomib dose | Standard Deviation 4.81 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M14 | 21.7 percentage of carfilzomib dose | Standard Deviation 7.59 |
| Carfilzomib - Moderate RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M15 | 0.776 percentage of carfilzomib dose | Standard Deviation 0.387 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M14 | 19.2 percentage of carfilzomib dose | Standard Deviation 4.36 |
| Carfilzomib - Severe RI | Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1 | M15 | 0.578 percentage of carfilzomib dose | Standard Deviation 0.23 |
Secondary
Plasma Protein Binding (PPB) of Carfilzomib
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
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Carfilzomib - Normal RF | Plasma Protein Binding (PPB) of Carfilzomib | 5 minutes after injection | 98.1 percentage of carfilzomib bound | Standard Deviation 0.5 |
| Carfilzomib - Normal RF | Plasma Protein Binding (PPB) of Carfilzomib | End of Injection | 97.8 percentage of carfilzomib bound | Standard Deviation 0.6 |
| Carfilzomib - Mild RI | Plasma Protein Binding (PPB) of Carfilzomib | 5 minutes after injection | 97.6 percentage of carfilzomib bound | Standard Deviation 1.6 |
| Carfilzomib - Mild RI | Plasma Protein Binding (PPB) of Carfilzomib | End of Injection | 97.6 percentage of carfilzomib bound | Standard Deviation 1.5 |
| Carfilzomib - Moderate RI | Plasma Protein Binding (PPB) of Carfilzomib | 5 minutes after injection | 98.2 percentage of carfilzomib bound | Standard Deviation 1.5 |
| Carfilzomib - Moderate RI | Plasma Protein Binding (PPB) of Carfilzomib | End of Injection | 98.4 percentage of carfilzomib bound | Standard Deviation 0.4 |
| Carfilzomib - Severe RI | Plasma Protein Binding (PPB) of Carfilzomib | End of Injection | 98.2 percentage of carfilzomib bound | Standard Deviation 0.5 |
| Carfilzomib - Severe RI | Plasma Protein Binding (PPB) of Carfilzomib | 5 minutes after injection | 98.1 percentage of carfilzomib bound | Standard Deviation 0.8 |
| Carfilzomib - Dialysis | Plasma Protein Binding (PPB) of Carfilzomib | 5 minutes after injection | 98.2 percentage of carfilzomib bound | Standard Deviation 0.4 |
| Carfilzomib - Dialysis | Plasma Protein Binding (PPB) of Carfilzomib | End of Injection | 97.6 percentage of carfilzomib bound | Standard Deviation 0.7 |
Secondary
Time to Progression (TTP)
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.
Population: Response Evaluable Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carfilzomib - Normal RF | Time to Progression (TTP) | 4.4 months |
| Carfilzomib - Mild RI | Time to Progression (TTP) | 5.6 months |
| Carfilzomib - Moderate RI | Time to Progression (TTP) | 2.8 months |
| Carfilzomib - Severe RI | Time to Progression (TTP) | 9.6 months |
| Carfilzomib - Dialysis | Time to Progression (TTP) | 6.5 months |