Phase 1
Completed N=26
Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease
Source: ClinicalTrials.gov NCT01949532 ↗Enrolled (actual)
26
Serious AEs
73.1%
Results posted
May 2016
Primary outcomePrimary: 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 — 563; 747 ng*h/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
563; 747 | — |
| PRIMARY 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 |
563; 752 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
1389; 1567 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
0.467; 0.467 | — |
| SECONDARY Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
0.341; 1.25 | — |
| SECONDARY Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
179; 134 | — |
| SECONDARY Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
0.135; 0.245 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2 |
24.1; 32.8 | — |
| SECONDARY 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 |
344; 480 | — |
| SECONDARY 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 |
347; 479 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
819; 1022 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
0.583; 0.467 | — |
| SECONDARY Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
0.387; 0.992 | — |
| SECONDARY Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
146; 93 | — |
| SECONDARY Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
0.222; 0.426 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1 |
32.0; 53.0 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14 |
320; 1486; 584; 2086 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14 |
355; 650 | — |
| SECONDARY Maximum Observed Plasma Concentration for Metabolite PR-389/M14 |
153; 413; 302; 595 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14 |
1.00; 1.50; 0.983; 2.00 | — |
| SECONDARY Terminal Half-life (T½) of Metabolite PR-389/M14 |
1.46; 1.10 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15 |
33.4; 54.6; 60.3; 86.3 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15 |
36.2; 66.4; 63.8; 131 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15 |
20.7; 25.9; 40.2; 42.3 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15 |
0.833; 0.767; 0.667; 0.750 | — |
| SECONDARY Terminal Half-life (T½) of Metabolite PR-413/M15 |
1.07; 1.41; 0.962; 1.37 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16 |
82.8; 86.8; 147; 138 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16 |
84.4; 89.6; 148; 139 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16 |
93.4; 90.4; 180; 151 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16 |
0.617; 0.600; 0.525; 0.533 | — |
| SECONDARY Terminal Half-life (T½) of Metabolite PR-519/M16 |
0.705; 0.721; 0.617; 0.687 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
15; 11; 12; 9; 10; 9 | — |
Eligibility Criteria
Key Inclusion Criteria
- Relapsed multiple myeloma
- Evaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria)
- Received at least 1 prior treatment regimen or line of therapy for multiple myeloma
- End-stage renal disease (ESRD) on hemodialysis or CrCl ≥ 75 mL/min
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
- Adequate organ and bone marrow function
- 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
- Immunoglobulin M (IgM) multiple myeloma
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Waldenström Macroglobulinemia
- Active congestive heart failure (NYHA Class III-IV) ischemia, conduction abnormalities
- Known human immunodeficiency virus (HIV), recent hepatitis B virus (HBV), hepatitis C virus (HCV)
- Myelodysplastic Syndrome
- Contraindication to test article, constituents, or required concomitant medications
- Other investigational drugs
Data sourced from ClinicalTrials.gov (NCT01949532). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.