CClinicalTrials.gg
Sign In
CompletedNCT01949532Updated May 2, 2017Results posted

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

A Phase 1 interventional study of Carfilzomib in Relapsed Multiple Myeloma and End-stage Renal Disease, sponsored by Amgen. Completed at 13 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-05-02.

Sponsored by Amgen · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
26
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to see how the body and the cancer react to carfilzomib, including measuring the amount of the study drug in the blood at certain times following dosing. This study is being done in people with normal kidney function and those with end-stage renal disease to see if they respond differently to the study drug.

Read the detailed description

Specifically, the purpose of this study is to assess the influence of end-stage renal disease (ESRD) on area under the curve (both area under the curve, from time 0 to the last concentration measured [AUC0-last] and area under the curve, from time 0 extrapolated to infinity [AUC0-inf]) of carfilzomib 56 mg/m² at Cycle 2 Day 1 (C2D1) in patients with relapsed multiple myeloma.

02

Conditions studied

  • Relapsed Multiple Myeloma
  • End-stage Renal Disease
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 26 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  1. Relapsed multiple myeloma
  2. Evaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria)
  3. Received at least 1 prior treatment regimen or line of therapy for multiple myeloma
  4. End-stage renal disease (ESRD) on hemodialysis or CrCl ≥ 75 mL/min
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  6. Adequate organ and bone marrow function
  7. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment

Key Exclusion Criteria:

  1. Immunoglobulin M (IgM) multiple myeloma
  2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  3. Waldenström Macroglobulinemia
  4. Active congestive heart failure (NYHA Class III-IV) ischemia, conduction abnormalities
  5. Known human immunodeficiency virus (HIV), recent hepatitis B virus (HBV), hepatitis C virus (HCV)
  6. Myelodysplastic Syndrome
  7. Contraindication to test article, constituents, or required concomitant medications
  8. Other investigational drugs
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Normal Renal Function

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

    Drug: Carfilzomib

  • Experimental
    End Stage Renal Disease

    Participants with end-stage renal disease (on hemodialysis) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.

    Drug: Carfilzomib

Interventions

  • DrugCarfilzomib

    Carfilzomib was administered by IV injection.

    Also known as: Kyprolis®

06

What researchers measure

Primary outcomes

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

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

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

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

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

Secondary outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  17. Maximum Observed Plasma Concentration for Metabolite PR-389/M14

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  30. Number of Participants With Adverse Events (AEs)

    Determination of the severity of all adverse events was assessed following the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Fatal. A Serious AE is an AE that meets one or more of the following criteria: * Death, * Life-threatening experience; * Requires in-patient hospitalization or prolongation of an existing hospitalization, * Results in persistent or significant disability/incapacity, * Is a congenital anomaly/birth defect, * Important medical events that may not result in death, be life-threatening, or require hospitalization. Treatment-related adverse events (TRAEs) are adverse events considered related to carfilzomib by the investigator, including those with unknown relationship.

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

07

Results

Posted May 4, 2016

Participant flow

Participants were enrolled at 13 investigative study centers (6 in the United States, 2 in Canada, and 5 in Australia) from 29 January 2014 to 25 March 2015. This study is ongoing, results are reported as of the data cut-off date of 12 October 2015.

Participant flow — Overall Study
MilestoneNormal Renal FunctionEnd Stage Renal Disease
Started1511
Completed128
Not completed33
Withdrew: On-study at the data cut-off date33

Outcome measures

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

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

Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2563 ± 41.9747 ± 143.9
Statistical analysis
  • Normal Renal Function vs End Stage Renal Disease · Ratio of geometric means: 132.75 · 90% CI 70.60 to 249.63The point estimates of the geometric mean ratios for the PK parameters were calculated by exponentiation of the differences in the least-squares means between the renal impairment group (test) and participants with normal renal function (reference).
PrimaryArea Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2563 ± 41.8752 ± 144.7
Statistical analysis
  • Normal Renal Function vs End Stage Renal Disease · Ratio of geometric means: 133.62 · 90% CI 70.93 to 251.73
SecondaryMaximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
ng/mLNormal Renal FunctionEnd Stage Renal Disease
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 21389 ± 26.81567 ± 128.8
SecondaryTime to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
hoursNormal Renal FunctionEnd Stage Renal Disease
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 20.467 (0.250 to 0.733)0.467 (0.250 to 0.583)
SecondaryTerminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
hoursNormal Renal FunctionEnd Stage Renal Disease
Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 20.341 (0.111 to 0.498)1.25 (0.0632 to 3.31)
SecondaryClearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · liters/hour
Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
liters/hourNormal Renal FunctionEnd Stage Renal Disease
Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2179 ± 38.9134 ± 136.9
SecondaryMean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · hours
Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
hoursNormal Renal FunctionEnd Stage Renal Disease
Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 20.135 ± 62.60.245 ± 79.9
SecondaryVolume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame:
Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · liters
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
litersNormal Renal FunctionEnd Stage Renal Disease
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 224.1 ± 44.832.8 ± 133.9
SecondaryArea Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1344 ± 24.8480 ± 36.0
SecondaryArea Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1347 ± 26.3479 ± 46.6
SecondaryMaximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
ng/mLNormal Renal FunctionEnd Stage Renal Disease
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1819 ± 29.81022 ± 37.2
SecondaryTime to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
hoursNormal Renal FunctionEnd Stage Renal Disease
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 10.583 (0.467 to 0.733)0.467 (0.233 to 0.750)
SecondaryTerminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
hoursNormal Renal FunctionEnd Stage Renal Disease
Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 10.387 (0.0938 to 0.599)0.992 (0.918 to 16.0)
SecondaryClearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · liters/hour
Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
liters/hourNormal Renal FunctionEnd Stage Renal Disease
Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1146 ± 23.093 ± 56.8
SecondaryMean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · hours
Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
hoursNormal Renal FunctionEnd Stage Renal Disease
Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 10.222 ± 16.60.426 ± 152.2
SecondaryVolume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame:
Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · liters
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
litersNormal Renal FunctionEnd Stage Renal Disease
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 132.0 ± 29.753.0 ± 185.5
SecondaryArea Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)320 ± 32.81486 ± 32.3
Cycle 2, Day 1 (n = 10, 8)584 ± 17.52086 ± 132.8
SecondaryArea Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16355 ± 25.1—
Cycle 2, Day 1650 ± 22.5—
SecondaryMaximum Observed Plasma Concentration for Metabolite PR-389/M14
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration for Metabolite PR-389/M14
ng/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)153 ± 25.4413 ± 32.9
Cycle 2, Day 1 (n = 10, 8)302 ± 16.5595 ± 128.4
SecondaryTime to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)1.00 (0.750 to 1.13)1.50 (1.00 to 2.67)
Cycle 2, Day 1 (n = 10, 8)0.983 (0.583 to 1.02)2.00 (1.45 to 4.47)
SecondaryTerminal Half-life (T½) of Metabolite PR-389/M14
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Terminal Half-life (T½) of Metabolite PR-389/M14
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 161.46 (0.975 to 1.73)—
Cycle 2, Day 11.10 (0.903 to 1.70)—
SecondaryArea Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)33.4 ± 53.954.6 ± 45.0
Cycle 2, Day 1 (n = 10, 8)60.3 ± 48.486.3 ± 199.1
SecondaryArea Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 7)36.2 ± 54.166.4 ± 48.7
Cycle 2, Day 1 (n = 10, 5)63.8 ± 48.0131 ± 35.8
SecondaryMaximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15
ng/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)20.7 ± 43.525.9 ± 42.5
Cycle 2, Day 1 (n = 10, 8)40.2 ± 38.542.3 ± 163.9
SecondaryTime to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)0.833 (0.683 to 1.00)0.767 (0.733 to 1.05)
Cycle 2, Day 1 (n = 10, 8)0.667 (0.250 to 1.00)0.750 (0.717 to 1.52)
SecondaryTerminal Half-life (T½) of Metabolite PR-413/M15
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Terminal Half-life (T½) of Metabolite PR-413/M15
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 7)1.07 (0.544 to 1.33)1.41 (1.30 to 1.86)
Cycle 2, Day 1 (n = 10, 5)0.962 (0.802 to 1.21)1.37 (1.04 to 1.44)
SecondaryArea Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)82.8 ± 53.186.8 ± 44.3
Cycle 2, Day 1 (n = 10, 8)147 ± 52.8138 ± 126.6
SecondaryArea Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16
ng*h/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)84.4 ± 52.489.6 ± 42.8
Cycle 2, Day 1 (n = 10, 8)148 ± 51.7139 ± 125.1
SecondaryMaximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16
ng/mLNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)93.4 ± 40.290.4 ± 48.0
Cycle 2, Day 1 (n = 10, 8)180 ± 40.5151 ± 129.7
SecondaryTime to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)0.617 (0.467 to 1.00)0.600 (0.467 to 0.917)
Cycle 2, Day 1 (n = 10, 8)0.525 (0.250 to 0.617)0.533 (0.467 to 0.750)
SecondaryTerminal Half-life (T½) of Metabolite PR-519/M16
Time frame:
Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Reported as:
Median · hours
Terminal Half-life (T½) of Metabolite PR-519/M16
hoursNormal Renal FunctionEnd Stage Renal Disease
Cycle 1, Day 16 (n = 13, 9)0.705 (0.473 to 0.993)0.721 (0.518 to 1.42)
Cycle 2, Day 1 (n = 10, 8)0.617 (0.555 to 0.673)0.687 (0.473 to 0.933)
SecondaryNumber of Participants With Adverse Events (AEs)

Determination of the severity of all adverse events was assessed following the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Fatal. A Serious AE is an AE that meets one or more of the following criteria: * Death, * Life-threatening experience; * Requires in-patient hospitalization or prolongation of an existing hospitalization, * Results in persistent or significant disability/incapacity, * Is a congenital anomaly/birth defect, * Important medical events that may not result in death, be life-threatening, or require hospitalization. Treatment-related adverse events (TRAEs) are adverse events considered related to carfilzomib by the investigator, including those with unknown relationship.

Time frame:
From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.
Reported as:
Number · participants
Number of Participants With Adverse Events (AEs)
participantsNormal Renal FunctionEnd Stage Renal Disease
Any adverse event1511
Adverse event ≥ Grade 3129
Serious adverse event109
AE leading to discontinuation of carfilzomib60
Fatal adverse events21
Treatment-related adverse events128
Treatment-related adverse event ≥ Grade 376
Serious treatment-related adverse event52
TRAE leading to discontinuation of carfilzomib40
Treatment-related fatal adverse events00

Adverse events

Collected over From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Normal Renal Function—10/15 (66.7%)14/15 (93.3%)
End Stage Renal Disease—9/11 (81.8%)10/11 (90.9%)
Most frequent serious events
Showing 10 of 35
Most frequent serious events
EventNormal Renal FunctionEnd Stage Renal Disease
PneumoniaInfections and infestations3/152/11
AnaemiaBlood and lymphatic system disorders0/152/11
AstheniaGeneral disorders0/152/11
PyrexiaGeneral disorders2/152/11
Lower respiratory tract infectionInfections and infestations1/152/11
HypotensionVascular disorders0/152/11
Acute kidney injuryRenal and urinary disorders2/150/11
CoagulopathyBlood and lymphatic system disorders0/151/11
Immune thrombocytopenic purpuraBlood and lymphatic system disorders0/151/11
LeukocytosisBlood and lymphatic system disorders0/151/11
Most frequent other events
Showing 10 of 169
Most frequent other events
EventNormal Renal FunctionEnd Stage Renal Disease
NauseaGastrointestinal disorders10/156/11
AnaemiaBlood and lymphatic system disorders8/155/11
FatigueGeneral disorders8/155/11
PyrexiaGeneral disorders8/152/11
ThrombocytopeniaBlood and lymphatic system disorders7/151/11
DiarrhoeaGastrointestinal disorders7/155/11
DyspnoeaRespiratory, thoracic and mediastinal disorders7/151/11
CoughRespiratory, thoracic and mediastinal disorders6/153/11
ConstipationGastrointestinal disorders2/154/11
VomitingGastrointestinal disorders3/154/11

Baseline characteristics

Age, Continuous
Age, Continuous(years)Normal Renal FunctionEnd Stage Renal DiseaseTotal
Mean64.8 ± 8.162.8 ± 7.964.0 ± 7.9
Sex: Female, Male
Sex: Female, Male(Participants)Normal Renal FunctionEnd Stage Renal DiseaseTotal
Female5611
Male10515
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Normal Renal FunctionEnd Stage Renal DiseaseTotal
Hispanic or Latino101
Not Hispanic or Latino14923
Unknown or Not Reported022
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Normal Renal FunctionEnd Stage Renal DiseaseTotal
Asian101
Black112
White12921
Other101
Not Reported011
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(participants)Normal Renal FunctionEnd Stage Renal DiseaseTotal
0 (Fully active)538
1 (Restrictive but ambulatory)10717
2 (Ambulatory but unable to work)011
08

Study locations

13 sites
  • Karmanos Cancer Institute
    Detroit, Michigan, United States
  • North Shore-LIJ Health System/Center for Advanced Medicine - North Shore University Hospital
    Lake Success, New York, United States
  • Gabrail Cancer Center
    Canton, Ohio, United States
  • Vanderbilt-Ingram Cancer Center, Henry-Joyce Cancer Clinic
    Nashville, Tennessee, United States
  • Baylor Charles A. Sammons Cancer Center
    Dallas, Texas, United States
  • UT Southwestern Medical Center
    Dallas, Texas, United States
  • Royal Prince Alfred Hospital
    Camperdown, New South Wales, Australia
  • Royal Brisbane and Women's Hospital
    Herston, Queensland, Australia
  • Monash Health, Monash Medical Centre
    Clayton, Victoria, Australia
  • St. Vincent's Hospital Melbourne
    Fitzroy, Victoria, Australia
  • The Alfred Hospital, Malignant Haematology and Stem Cell Transplant Department
    Melbourne, Victoria, Australia
  • QEII Health Sciences Centre
    Halifax, Nova Scotia, Canada
  • Sir Mortimer B. Davis-Jewish General Hospital
    Montreal, Quebec, Canada
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 2, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01949532
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Sep 24, 2013
Start date
Jan 2014
Primary completion
Apr 2015
Completion
Jan 2017
Results posted
May 4, 2016
Last update
May 2, 2017

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Multiple Myeloma→

Other studies from this sponsor

Amgen

Start the discussion