This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease (NCT01949532), a non-randomized phase 1 study. The primary outcome is 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.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01949532 |
| Phase | Phase 1 |
| Condition | Relapsed Multiple Myeloma, End-stage Renal Disease |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Participants with relapsed multiple myeloma, including people with normal renal function and people with end-stage renal disease who were on hemodialysis. The registry lists an enrollment of 26.
Intervention
Carfilzomib, administered by intravenous infusion. The study assessed drug concentrations in blood after dosing and recorded safety outcomes.
Comparator
The cohort with normal renal function is compared descriptively with the cohort with end-stage renal disease. Allocation was non-randomized, so the cohorts are not like-for-like randomized control groups.
Primary question
What is the area under the plasma concentration-time curve from time zero to the last measured concentration after carfilzomib at 56 mg/m² on cycle 2, day 1, and how does pharmacokinetic behavior relate to renal-function group?
The study’s stated purpose was to assess how the body and cancer respond to carfilzomib, including measuring the amount of drug in blood at specified times after dosing. The clinical question is therefore primarily about pharmacokinetics: how carfilzomib concentrations change over time, and whether the observed drug exposure differs between participants with normal renal function and those with end-stage renal disease.
The registered primary outcome is AUC0-last following 56 mg/m² on cycle 2, day 1. It describes cumulative plasma exposure over the period from dosing to the last measured concentration. The endpoint is reported as a geometric mean with geometric coefficient of variation, but the numerical group results and any comparison estimate are not reported in the registry record.
This is not a randomized treatment-effect question. Both cohorts received carfilzomib, and renal-function status defined the groups. Differences between cohorts could reflect renal status as well as other differences between the participants. The registry record does not report an adjusted comparison that would separate those influences. The results should thus be read as pharmacokinetic and safety observations from the enrolled cohorts, not as evidence from a randomized comparison.
3. Trial Design
The registry describes a phase 1, open-label study with non-randomized allocation and a parallel model. Its official title calls it a single-arm study, while the listed arms distinguish participants with normal renal function from participants with end-stage renal disease. These are two renal-function cohorts receiving carfilzomib, not randomized treatment arms. The record explicitly cautions that they are not a like-for-like control comparison.
The study enrolled 26 participants with relapsed multiple myeloma and renal disease categories of interest. The normal renal function group is defined in the arm description as having creatinine clearance of at least 75 mL/min. The end-stage renal disease group is described as being on hemodialysis. The recorded study status is completed; the recorded start is 2014-01, and primary completion is 2015-04.
Carfilzomib is the listed intervention. Both arm descriptions begin with dosing at 20 mg/m² by intravenous infusion on days 1 and 2 of cycle 1, followed by 27 mg/m² on days 8, 9, 15, and 16 of cycle 1. The arm descriptions then refer to participants who adequately tolerated dosing at 27 mg/m², but the normal renal function description is truncated, so the subsequent regimen for that group is not fully available in the registry record. The end-stage renal disease description names 56 mg/m² after that step. The primary pharmacokinetic outcome concerns 56 mg/m² on cycle 2, day 1.
Open-label means that masking was not used. The registry record does not report a randomized assignment process, a blinded outcome assessment, or a separate untreated control group. The study’s design is suited to describing pharmacokinetic measurements and safety observations in these cohorts. It cannot, on its own, eliminate confounding between the groups or establish that any observed difference is caused by renal-function status.
The record lists 32 outcome measures and 2 analyses. It does not report the full protocol or a complete statistical analysis plan. Details such as the rationale for the enrollment target, prespecified comparison methods, or any interim analyses are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants with relapsed multiple myeloma were enrolled into cohorts according to renal function (normal creatinine clearance (CrCl) or end-stage renal disease (ESRD; patients on hemodialysis)). Renal function was based on calculated CrCl using the Cockcroft-Gault formula at baseline.
Overall Study
| Stage | Normal Renal Function | End Stage Renal Disease |
|---|---|---|
| STARTED | 15 | 11 |
| COMPLETED | 12 | 8 |
| NOT COMPLETED | 3 | 3 |
Reasons for not completing this period:
| Reason | Normal Renal Function | End Stage Renal Disease |
|---|---|---|
| On-study at the Data Cut-off Date | 3 | 3 |
Analysis population for the primary outcome, as defined in the registry: PK evaluable population for cycle 2, day 1. The PK evaluable population is defined as participants with sufficient carfilzomib plasma concentration versus time data for the estimation of PK parameters by non-compartmental analysis on cycle 1, day 16 and/or cycle 2, day 1. One participant was excluded due to samples taken from the infusion arm.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Normal Renal Function | End Stage Renal Disease | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 11 | 26 | |
| Age, Continuous | years | 64.8 (SD 8.1) | 62.8 (SD 7.9) | 64.0 (SD 7.9) |
| Sex: Female, Male: Female | Participants | 5 | 6 | 11 |
| Sex: Female, Male: Male | Participants | 10 | 5 | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 | 9 | 23 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Asian | participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Black | participants | 1 | 1 | 2 |
| Race/Ethnicity, Customized: White | participants | 12 | 9 | 21 |
| Race/Ethnicity, Customized: Other | participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Not Reported | participants | 0 | 1 | 1 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 (Fully active) | participants | 5 | 3 | 8 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: 1 (Restrictive but ambulatory) | participants | 10 | 7 | 17 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: 2 (Ambulatory but unable to work) | participants | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as 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, measured over 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..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng*h/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the plasma concentration-time curve from time zero to the last measured concentration, AUC0-last, after carfilzomib at 56 mg/m² on cycle 2, day 1. Its unit is ng*h/mL. The registry reports that the endpoint is summarized using a geometric mean and a geometric coefficient of variation. The endpoint’s numerical results are not reported in the registry record.
AUC represents drug exposure across a period of time: it combines information from the measured concentrations and the timing of those measurements. AUC0-last covers the observed period through the final concentration used in the calculation. It does not itself describe the concentration at a particular moment, the time at which the peak occurred, or the full concentration curve beyond the last measurement.
The registered sampling schedule on cycle 2, day 1 includes predose, measurements during infusion, and measurements at specified intervals after infusion ends. Carfilzomib plasma concentrations for pharmacokinetic analyses were measured by liquid chromatography with tandem mass spectrometry. The assay’s lower limit of quantitation was 0.3 ng/mL.
General explanation: pharmacokinetic endpoints are used to characterize how a drug is absorbed, distributed, and cleared, and to compare exposure patterns across groups or dosing conditions. AUC is useful because it summarizes exposure over the measured period rather than relying on a single concentration. The geometric mean is commonly used when positive measurements are right-skewed or when relative differences are of interest. The geometric coefficient of variation describes spread on a multiplicative scale; it is not the same as a confidence interval and does not express the precision of a group comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a pharmacokinetic primary endpoint but does not report its numerical value, the geometric coefficient of variation, or a confidence interval. It also does not report a numerical contrast between the normal renal function and end-stage renal disease cohorts for the primary endpoint. Consequently, the size and precision of any difference in AUC0-last cannot be assessed from the registry record.
The study’s enrollment of 26 describes the planned or recorded overall enrollment, not the number contributing to every pharmacokinetic analysis. The primary endpoint population is described as the PK-evaluable population for cycle 2, day 1. That population is defined by having sufficient plasma concentration-time data for estimation of pharmacokinetic parameters by non-compartmental analysis on cycle 1, day 16 and/or cycle 2, day 1. The description also notes that one participant was excluded, but the registry wording is incomplete and does not establish the context of that exclusion. Group-specific analysis counts are not reported in the registry record.
The design requires caution when considering differences between renal-function groups. Participants were not randomized to renal-function status, and all received carfilzomib. Differences in participant characteristics or clinical circumstances could accompany differences in renal function. Without a reported adjusted analysis and enough detail to evaluate it, an observed difference would be an association between cohort membership and pharmacokinetic measurement, not a causal estimate of the effect of renal disease.
The reported serious adverse event figures describe participants affected within each cohort. In the normal renal function group, 10 of 15 participants were recorded as having a serious adverse event; in the end-stage renal disease group, 9 of 11 were recorded as affected. Other adverse events were recorded for 14 of 15 and 10 of 11 participants, respectively. These figures describe event occurrence in the enrolled cohorts and do not establish a comparative safety effect. The registry lists serious adverse event terms and percentages, but the record does not supply enough context to interpret them as comparative rates adjusted for exposure time or baseline differences.
General explanation: a confidence interval, when reported, communicates uncertainty around an estimate across values compatible with the analysis and data under its assumptions. It is distinct from the geometric coefficient of variation, which describes dispersion among measurements. Neither the primary endpoint estimate nor a confidence interval is reported in the registry record, so the precision of the primary pharmacokinetic comparison cannot be judged.
General explanation: a non-randomized cohort comparison can be informative for describing measurements in specific groups, but it is vulnerable to confounding. Statistical adjustment may address measured differences, but it cannot guarantee that all relevant differences have been accounted for. The registry record does not report enough analysis detail to assess such adjustment.
9. Statistical Methods Explained
The registry’s primary pharmacokinetic measure is AUC0-last, summarized by a geometric mean and geometric coefficient of variation. The endpoint is measured after carfilzomib at 56 mg/m² on cycle 2, day 1, using plasma concentrations collected at prespecified times. The record names non-compartmental analysis as the approach for estimating pharmacokinetic parameters in the PK-evaluable population. It does not report the numerical endpoint estimates or a complete statistical analysis plan.
What does AUC0-last represent?
General explanation: a concentration-time curve traces measured drug concentration against elapsed time after a dose. The area under that curve summarizes exposure across the observed interval. AUC0-last starts at time zero and ends at the last concentration included in the analysis. It is therefore tied to the sampling schedule and the available measurements. It is not automatically an estimate of exposure over an unlimited period; the registered endpoint specifically ends at the last concentration.
The registry lists sampling before dosing, during infusion, and after the infusion ends. These measurements provide observations from which the concentration-time profile and AUC can be estimated. The assay method is liquid chromatography with tandem mass spectrometry, and its lower limit of quantitation is 0.3 ng/mL. The registry does not report how concentrations below that limit were handled in the analysis.
Why use a geometric mean?
General explanation: pharmacokinetic measurements are positive and may vary proportionally rather than by a fixed additive amount. A geometric mean summarizes measurements on a multiplicative scale. It is obtained by averaging after a logarithmic transformation and transforming the result back to the original scale. This can be appropriate when the distribution is skewed, but interpretation still depends on the observed data and analysis assumptions. The geometric mean does not reveal the full distribution, and it does not by itself quantify uncertainty about a comparison.
The registry pairs the geometric mean with a geometric coefficient of variation. General explanation: this coefficient describes relative variability on a multiplicative scale. Greater variability means measurements are more dispersed relative to their central value. It is a measure of spread, not a standard error, confidence interval, or test of a group difference. The numerical coefficient for the primary endpoint is not reported in the registry record.
What is non-compartmental analysis?
General explanation: non-compartmental analysis estimates pharmacokinetic quantities directly from observed concentration-time data without requiring the analyst to specify a particular compartment structure for the body. AUC and other parameters depend on the sampling observations and the estimation rules used. The registry names this analysis approach for the PK-evaluable population, but the detailed calculation rules, software, transformations, and handling of incomplete profiles are not reported in the registry record.
The PK-evaluable population is described as participants with sufficient plasma concentration-versus-time data for estimating pharmacokinetic parameters on cycle 1, day 16 and/or cycle 2, day 1. This definition matters because the enrolled population and the population with evaluable measurements may differ. The record’s description states that one participant was excluded, but the available wording does not fully explain the exclusion. The analysis count by cohort is not reported.
Why does non-randomized allocation matter?
General explanation: randomization is intended to balance both measured and unmeasured participant characteristics across treatment groups on average. In this study, cohort membership reflects renal-function group rather than randomized assignment. A difference in pharmacokinetic measurements could therefore be associated with renal status, but it could also reflect other differences between the groups. A statistical adjustment can address measured covariates if appropriately specified and available, but it cannot remove all possible confounding. The registry record does not report an adjusted model for the primary endpoint.
The trial is open-label, with no masking. Pharmacokinetic concentrations are laboratory measurements, but the registry record does not report whether laboratory personnel or those conducting analysis were blinded to cohort. No claim about blinding beyond the registered masking status can be made.
How should planning calculations be read?
General explanation: sample-size calculations based on an observed effect are planning illustrations. They explore how many participants might be needed under stated assumptions to detect an effect of a chosen size at a chosen significance level and power. They are not a description of the study’s original enrollment rationale, and they are not observed power. A sample-size result depends on assumptions such as the effect size, variability, allocation, and statistical test. The registry record does not report that the trial was designed using those later illustrative assumptions.
The planning description specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not establish that the actual study used that analysis. The record does not report the original sample-size justification or the results needed to judge whether a particular planning illustration is informative for this trial.
General explanation: over-dispersion occurs when the observed variability is greater than a model assumes. If a method assumes less variability than the data contain, standard errors may be too small and intervals may appear too narrow. Pharmacokinetic data can vary substantially between participants, so the variability measure and analysis model matter. The registry names a geometric coefficient of variation but does not report its value, a model for between-participant variation, or a method for handling over-dispersion.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 32 outcome measures, including the primary AUC0-last endpoint and secondary pharmacokinetic outcomes such as maximum observed concentration, time to maximum concentration, terminal half-life, clearance, mean residence time, volume of distribution at steady state, and additional AUC measures. It lists 2 analyses. The numerical results for the primary endpoint and the listed secondary outcomes are not reported in the registry record.
When a study examines many outcomes, the chance of at least one apparently unusual result can increase if each is tested separately. General explanation: multiplicity procedures can control this risk by adjusting significance thresholds or by defining a hierarchy of outcomes. The registry record does not report whether multiplicity was addressed, whether secondary analyses were considered exploratory, or whether an outcome hierarchy was prespecified. No correction or unadjusted testing approach should be assumed.
The record identifies a PK-evaluable population for cycle 2, day 1 and describes its eligibility in terms of sufficient concentration-time data for non-compartmental parameter estimation on cycle 1, day 16 and/or cycle 2, day 1. It also notes that one participant was excluded, but the exclusion description is incomplete. The number of participants contributing to each endpoint, the extent of missing measurements, and the handling of missing concentration data are not reported in the registry record.
General explanation: missingness can affect an analysis when the availability of measurements is related to participant characteristics, tolerability, or the outcome itself. Complete-case analyses may describe only participants with usable data. Imputation or other missing-data methods require assumptions, which should be stated and evaluated. The registry record does not report an imputation method, a sensitivity analysis, or enough detail to determine how incomplete profiles influenced the estimates.
The planned enrollment and the analysis population are not interchangeable. The registry lists enrollment of 26, but it does not provide endpoint-specific denominators or a participant flow description for the pharmacokinetic outcomes. Without those details, it is not possible to determine how much information supported each estimate or whether missingness differed by renal-function cohort.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Normal Renal Function | 10 | 15 | 66.7% |
| End Stage Renal Disease | 9 | 11 | 81.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Normal Renal Function | 14 of 15 |
| End Stage Renal Disease | 10 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Normal Renal Function | End Stage Renal Disease |
|---|---|---|---|
| Pneumonia | Infections and infestations | 3 of 15 | 2 of 11 |
| Pyrexia | General disorders | 2 of 15 | 2 of 11 |
| Lower respiratory tract infection | Infections and infestations | 1 of 15 | 2 of 11 |
| Anaemia | Blood and lymphatic system disorders | 0 of 15 | 2 of 11 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 15 | 1 of 11 |
| Atrial fibrillation | Cardiac disorders | 1 of 15 | 1 of 11 |
| Asthenia | General disorders | 0 of 15 | 2 of 11 |
| Death | General disorders | 1 of 15 | 1 of 11 |
| Acute kidney injury | Renal and urinary disorders | 2 of 15 | 0 of 11 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Renal Function | End Stage Renal Disease |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 10 of 15 | 6 of 11 |
| Anaemia | Blood and lymphatic system disorders | 8 of 15 | 5 of 11 |
| Fatigue | General disorders | 8 of 15 | 5 of 11 |
| Diarrhoea | Gastrointestinal disorders | 7 of 15 | 5 of 11 |
| Pyrexia | General disorders | 8 of 15 | 2 of 11 |
| Cough | Respiratory, thoracic and mediastinal disorders | 6 of 15 | 3 of 11 |
| Thrombocytopenia | Blood and lymphatic system disorders | 7 of 15 | 1 of 11 |
| Headache | Nervous system disorders | 5 of 15 | 3 of 11 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 7 of 15 | 1 of 11 |
| Vomiting | Gastrointestinal disorders | 3 of 15 | 4 of 11 |
Serious events with the highest arm-level rate: pneumonia (20.0%), anaemia (18.2%), asthenia (18.2%), pyrexia (18.2%), lower respiratory tract infection (18.2%).
The registry reports serious and other adverse event counts by renal-function group. In the normal renal function group, 10 of 15 participants were recorded as affected by serious adverse events and 14 of 15 by other adverse events. In the end-stage renal disease group, the corresponding counts were 9 of 11 and 10 of 11. These are participant counts within each group, not randomized comparisons.
The listed serious adverse event terms include pneumonia at 20.0%, and anaemia, asthenia, pyrexia, and lower respiratory tract infection at 18.2% each, as well as hypotension at 18.2%. These percentages are reported as serious-event terms; the registry record does not provide further detail about event counts by cohort, exposure time, or whether participants could contribute more than one term.
General explanation: an adverse-event count indicates how many participants were recorded with an event under the registry’s reporting definitions. It does not by itself measure severity beyond the stated serious classification, duration, recurrence, causal relation to treatment, or risk over time. Participants may have more than one event, so event-term percentages need not add to a total proportion of affected participants.
The record does not report death counts. Because allocation was non-randomized and the groups differ by renal-function status, the figures should be read as descriptive safety observations, not as evidence that one cohort had greater or lesser treatment-related risk.
12. What the Result Does, and Does Not, Mean
This study addresses a focused statistical question: how carfilzomib exposure, measured by plasma concentration over time, is characterized in participants with normal renal function and participants with end-stage renal disease. Its primary endpoint is AUC0-last after 56 mg/m² on cycle 2, day 1. The endpoint choice is relevant to pharmacokinetic characterization because it summarizes measured exposure across a defined sampling interval.
The registry record does not report the primary endpoint’s geometric mean, geometric coefficient of variation, confidence interval, or numerical comparison between cohorts. It therefore does not allow a reader to judge the magnitude or precision of a difference in the primary pharmacokinetic measure. The registered endpoint name and analysis population describe what was intended to be assessed, but they do not substitute for the outcome values.
The study also records safety outcomes. The serious and other adverse-event participant counts and the listed serious-event percentages provide descriptive information about events recorded in the enrolled cohorts. They do not by themselves establish comparative safety, causality, or risk over a common period of exposure. Death counts are not reported in the registry record.
The study does not provide a randomized comparison of carfilzomib against another treatment or no treatment. Both renal-function cohorts received carfilzomib, and cohort membership was not randomized. Any group difference could reflect renal function, other differences between participants, or both. The record does not report an adjusted comparison that would resolve this issue.
General explanation: an estimate describes the observed data under an analysis method; its precision depends on factors such as sample size, variability, and missing information. A confidence interval, if available, would help express uncertainty, while a point estimate alone would not. Neither is reported for the primary endpoint in the registry record. The study can be understood as a small phase 1 pharmacokinetic and safety investigation, but its registered information does not support a numerical conclusion about the size or precision of the primary contrast.
These limitations do not erase the descriptive role of the study. They define the boundary of what can be inferred from the record: the design and endpoint are documented, while the numerical primary results and enough detail for a complete evaluation of comparative analyses are not.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the distinction between a pharmacokinetic study and a randomized treatment-effect trial. The central measure is drug exposure, not a randomized contrast in clinical outcomes. The two cohorts are defined by renal-function status, and non-randomized allocation means that differences cannot automatically be attributed to that status alone.
The endpoint also highlights why measurement design matters. AUC0-last depends on repeated plasma concentration measurements at stated times and on which observations are available for analysis. The registry identifies the sampling schedule, assay approach, lower limit of quantitation, and a PK-evaluable population. These details help define what the endpoint represents and where its observed interval ends.
The statistical summary matters as well. A geometric mean and geometric coefficient of variation suit a multiplicative description of pharmacokinetic data, but they answer different questions: one describes a central value and the other relative variability. Neither is a substitute for an estimate of the between-cohort contrast with uncertainty. Since those numerical results are not reported in the registry record, the precision of the primary comparison cannot be assessed.
Safety summaries also require context. Counts of participants affected and percentages for event terms are useful descriptions, but they do not establish causality or account for differing participant characteristics or exposure duration. The non-randomized design is relevant to both pharmacokinetic and safety interpretation.
Finally, the record demonstrates why outcome registration and outcome reporting are distinct. A listed endpoint indicates what was to be measured; a reader also needs the estimate, variability, analysis population, and methods to judge the result. The registry record identifies the intended pharmacokinetic question and aspects of the measurement process, but it does not report enough numerical outcome information to assess the primary result’s size or precision.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for statistical interpretation is that the registry record does not report the numerical primary endpoint results. The geometric mean and geometric coefficient of variation are specified as summary measures, but their values, a confidence interval, and a cohort contrast are absent. This prevents assessment of the observed AUC0-last difference and its precision.
The non-randomized design limits causal interpretation. The normal renal function and end-stage renal disease cohorts are not like-for-like randomized groups, and the record does not report an adjusted primary comparison. Differences in other participant characteristics could be associated with both cohort membership and measured pharmacokinetics.
The available arm descriptions are incomplete. The normal renal function description is truncated after noting that participants who tolerated dosing at 27 mg/m² received further carfilzomib; the subsequent dose and schedule are not fully reported in the record. The end-stage renal disease description names 56 mg/m², which is also the dose used for the registered primary endpoint. This incompleteness limits reconstruction of the full treatment schedule from the registry text.
The analysis population description is also incomplete. It defines PK-evaluable participants by sufficient concentration-time data and notes that one participant was excluded, but does not complete the explanation. Endpoint-specific denominators, details of missing measurements, rules for concentrations below the assay limit, and sensitivity analyses are not reported in the registry record.
Multiplicity handling, the original sample-size justification, interim analyses, and full statistical analysis methods are not reported. The listed safety counts do not include death counts, and the record does not provide sufficient context to interpret the serious-event percentages as comparative rates or as treatment-attributable outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease — NCT01949532.
- Registry record last updated 2017-05-02; status last verified 2017-04.
- Results first posted 2016-05-04.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed, open-label, phase 1 study of carfilzomib in participants with relapsed multiple myeloma and different renal-function categories. Enrollment was 26. The study is listed as non-randomized and parallel, with cohorts of normal renal function and end-stage renal disease on hemodialysis.
The primary outcome is AUC0-last after carfilzomib at 56 mg/m² on cycle 2, day 1, summarized by geometric mean and geometric coefficient of variation. Plasma concentrations were measured by liquid chromatography with tandem mass spectrometry, with a lower limit of quantitation of 0.3 ng/mL. The primary numerical result and its precision are not reported in the registry record.
The registry lists pharmacokinetic secondary outcomes and safety findings. Adverse-event counts are reported by cohort, while death counts are not reported. Because the cohorts were not randomized, their results are descriptive rather than a like-for-like treatment comparison. The record does not report the full statistical analysis plan, original sample-size justification, or complete details of missing-data handling.