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 Advanced Malignancies and Hepatic Impairment (NCT01949545), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 27 mg/m².
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01949545 |
| Phase | Phase 1 |
| Condition | Solid Tumors, Hematologic Malignancies, Hepatic Impairment |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 46 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced malignancies were grouped by hepatic function: normal hepatic function, mild hepatic impairment, moderate hepatic impairment, or severe hepatic impairment. The listed conditions include solid tumors, hematologic malignancies, and hepatic impairment. The primary endpoint population was pharmacokinetic-evaluable: participants who received the intended carfilzomib dose, 27 or 56 mg/m², and had concentration-versus-time data sufficient to estimate each pharmacokinetic parameter by non-compartmental analysis.
Intervention
Carfilzomib was administered by intravenous infusion. The arm descriptions state that participants started at 20 mg/m² on days 1 and 2 of cycle 1, with a planned step-up to 27 mg/m² on specified later days in cycle 1. The descriptions are truncated in the registry record, so further dosing details are not reported in the registry record.
Comparator
There was no separate untreated or active-control arm. The four groups represent hepatic-function categories within a non-randomized, single-arm study, not randomized treatment groups. The registry record does not establish that the groups were otherwise comparable, so differences between them should not be read as causal effects of hepatic impairment.
Primary question
The primary endpoint was the area under the plasma concentration-time curve from the start of infusion to the last measured concentration, AUC0-last, after carfilzomib 27 mg/m² on day 16 of cycle 1. The study was designed to characterize carfilzomib pharmacokinetics and safety across hepatic-function groups. Numerical AUC0-last results by group are not reported in the registry record.
Although the brief summary mentions safety and efficacy, the listed primary endpoint is pharmacokinetic, not an efficacy endpoint. The registry record lists additional pharmacokinetic outcomes, including maximum concentration, time to maximum concentration, clearance, terminal half-life, mean residence time, volume of distribution, and area-under-the-curve measures at another dose. It does not report numerical results for those outcomes in the record.
3. Trial Design
NCT01949545 is described as an open-label, single-arm, Phase 1 study. It was non-randomized and had no masking. The record describes a parallel model with four groups defined by hepatic function: normal, mild impairment, moderate impairment, and severe impairment. Because treatment was not randomly allocated and there was no distinct control arm, the group structure is descriptive rather than a randomized comparison of treatments.
The registry lists an enrollment of 46. Amgen is identified as the sponsor, and the study status is completed. The recorded start is 2013-10 and the primary completion is 2015-08. These dates describe the registry record; they do not establish when every participant completed follow-up.
All groups received carfilzomib. The arm descriptions specify an initial dose of 20 mg/m² by intravenous infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² on days 8, 9, 15, and 16 of cycle 1. The descriptions include further conditions about tolerating treatment, but their text is incomplete in the registry record. Details beyond the available descriptions are not reported in the registry record.
The primary pharmacokinetic outcome concerns carfilzomib 27 mg/m² on cycle 1 day 16. Sampling was specified before dosing, during and at the end of infusion, and at several times after infusion. The primary analysis population is defined by intended dose and evaluable concentration-time data, rather than simply by enrollment. The number of participants in that population by hepatic-function group is not reported in the registry record.
The study is not a like-for-like controlled comparison. Hepatic-function categories may differ in clinical characteristics, and the record does not report randomization or adjustment methods that would make group contrasts causal. The registry record also does not report a trial-specific sample-size justification, a detailed statistical analysis plan, or interim analyses.
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 were assigned to 1 of 4 cohorts with varying degrees of hepatic impairment defined by the National Cancer Institute Organ Dysfunction Working Group Criteria (NCI-ODWG) schema for hepatic function. Completed indicates participants who completed the safety follow-up visit 30 days after the last dose of carfilzomib.
Overall Study
| Stage | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|
| STARTED | 11 | 17 | 14 | 4 |
| COMPLETED | 11 | 17 | 14 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic-evaluable population, defined as participants who received the intended carfilzomib dose (27 or 56 mg/m²) and who had plasma concentration versus time data for the estimation of each pharmacokinetic (PK) parameter by a non-compartmental analysis.
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 Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 11 | 17 | 14 | 4 | 46 | |
| Age, Continuous | years | 68.5 (SD 8.2) | 59.5 (SD 9.1) | 61.0 (SD 7.9) | 56.3 (SD 10.9) | 61.8 (SD 9.3) |
| Age, Customized: < 65 years | participants | 3 | 12 | 8 | 3 | 26 |
| Age, Customized: ≥ 65 years | participants | 8 | 5 | 6 | 1 | 20 |
| Sex: Female, Male: Female | Participants | 2 | 8 | 5 | 3 | 18 |
| Sex: Female, Male: Male | Participants | 9 | 9 | 9 | 1 | 28 |
| Race/Ethnicity, Customized: Black | participants | 0 | 1 | 1 | 0 | 2 |
| Race/Ethnicity, Customized: White | participants | 11 | 13 | 13 | 4 | 41 |
| Race/Ethnicity, Customized: Not reported | participants | 0 | 3 | 0 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 27 mg/m², measured over Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) 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*hr/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is AUC0-last for carfilzomib 27 mg/m² on day 16 of cycle 1. AUC0-last represents the area under the plasma concentration-time curve from the start of the infusion to the last concentration measured. It combines information across the sampling period into a measure of drug exposure over time. The registry describes calculation from individual plasma concentration profiles using a non-compartmental approach.
Pharmacokinetic exposure measures are used to characterize how drug concentrations change after administration. Comparing exposure summaries across hepatic-function categories can help describe whether the observed concentration profiles differ among those groups. Such a comparison is descriptive in this non-randomized design; it does not by itself establish that hepatic impairment caused a difference.
The registry specifies that the primary endpoint is summarized as a geometric mean, with geometric coefficient of variation as the dispersion measure. A geometric mean is used for positive measurements that may be right-skewed; it summarizes values on a multiplicative rather than additive scale. The coefficient of variation expresses relative spread around the geometric mean. These are general interpretations of the statistical measures, not additional findings from the trial.
The record gives the endpoint definition and sampling schedule but does not report group-specific geometric means, dispersion estimates, confidence intervals, or formal comparison results. Therefore, the magnitude and precision of any between-group differences in AUC0-last are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and the way the primary pharmacokinetic endpoint was defined, but it does not provide numerical primary endpoint results. In particular, it does not report AUC0-last estimates for the normal, mild, moderate, or severe hepatic-function groups. Without those estimates and their uncertainty, the direction, size, and precision of differences in drug exposure cannot be assessed from the registry record.
The record identifies a pharmacokinetic-evaluable population: participants who received the intended carfilzomib dose, 27 or 56 mg/m², and had plasma concentration-versus-time data that allowed non-compartmental estimation of each parameter. This definition is narrower than the enrolled population. The number evaluable for the primary endpoint, and the number contributing to each group estimate, are not reported in the registry record. Enrollment alone should not be treated as the denominator for the pharmacokinetic analysis.
The design also limits interpretation of any group contrast. Participants were not randomized to hepatic-function categories, and all groups received carfilzomib. The groups are not a treatment arm and a control arm. Differences in their observed outcomes could reflect group composition or other factors as well as hepatic function. The registry record does not report an adjusted analysis that would address such differences. Thus, even if numerical contrasts were available, they would describe observed group differences rather than establish a causal effect of hepatic impairment.
The endpoint is one of several registered pharmacokinetic measures. Secondary outcomes include maximum plasma concentration, time to maximum concentration, clearance, terminal half-life, mean residence time, volume of distribution at steady state, and AUC measures at 56 mg/m². Their numerical results and their relationship to the primary endpoint are not reported in the registry record. The brief summary also refers to efficacy, but no efficacy endpoint or efficacy result is specified in the registry record for this analysis.
Safety counts are reported separately by hepatic-function group. The registry lists participants with serious adverse events and participants with other adverse events, along with selected serious-event terms. Those figures describe observed events in this study; they do not provide a controlled estimate of excess risk. Death counts are not reported in the registry record. The small severe-impairment group, with 4 participants at risk for the reported safety categories, also means that its observed counts should be read as a description of those participants, not as a precise estimate for a broader population.
In short, the record supports a clear account of the study design, endpoint definition, and reported safety counts, but it does not support a conclusion about the size or statistical precision of pharmacokinetic differences among hepatic-function groups. Statistical significance, confidence intervals, and sponsor conclusions for the primary endpoint are not reported in the registry record.
9. Statistical Methods Explained
The registry describes a geometric-mean pharmacokinetic endpoint based on individual concentration-time profiles. Its statistical meaning depends on the endpoint definition, the population with usable concentration data, and the way uncertainty is summarized. Numerical estimates and a detailed analysis plan are not reported in the registry record, so the explanations below describe the listed methods generally rather than reconstructing unreported analyses.
What does AUC0-last measure?
AUC0-last is the area under the concentration-time curve from the start of the infusion to the last measured concentration. Each participant’s plasma concentrations over the scheduled sampling times contribute to that participant’s profile. A non-compartmental approach estimates the area from the observed profile without requiring a specified compartment model. The endpoint therefore summarizes exposure across the observed interval; it is not a single concentration at one sampling time.
The time schedule matters because estimates depend on the available concentration measurements. For the primary endpoint, sampling was specified on cycle 1 day 16 before dosing, during infusion, at the end of infusion, and at post-infusion times through 4 hours. The registry identifies the schedule but does not report missed-sample handling, assay details, or the exact integration procedures beyond the non-compartmental description.
Why use a geometric mean?
Pharmacokinetic measurements are positive and often vary multiplicatively. A geometric mean is a suitable summary when the distribution is more naturally considered on a log scale than as symmetric additive deviations around an arithmetic mean. In general, taking logs converts multiplicative differences into additive ones; averaging on that scale and converting back gives a geometric mean. This general explanation does not imply that any particular distributional assumption was verified in this study.
The geometric coefficient of variation describes relative variability on a multiplicative scale. It is not the same as a standard deviation in the original units. Reading it alongside a geometric mean can convey both a typical exposure level and how dispersed participant values are relative to that level. The actual values are not reported in the registry record.
What would a confidence interval add?
In general, a confidence interval gives a range of values compatible with the data and the specified statistical procedure. It communicates estimation uncertainty, rather than only providing a point estimate. For a comparison of exposure across hepatic-function categories, an interval around a ratio or other contrast could show whether the data are compatible with a range of group differences. The registry record does not report confidence intervals or the exact contrast scale, so no interval-based interpretation is possible.
A p-value, if reported, would address compatibility of data with a specified null model under the analysis assumptions; it would not measure the probability that the null hypothesis is true or the clinical importance of an observed difference. The primary endpoint’s p-value and any formal hypothesis tests are not reported in the registry record.
Why does the evaluable population matter?
The primary analysis population is defined by receipt of the intended carfilzomib dose and availability of concentration-versus-time data sufficient to estimate the parameters. This makes pharmacokinetic evaluability dependent on both treatment receipt and data availability. Participants who enrolled but lacked an adequate profile may not contribute to an endpoint estimate. The record does not state how many were excluded from this population, whether exclusions differed by hepatic-function group, or how incomplete profiles were handled.
When data are missing, the reason and pattern can affect interpretation. As a general statistical matter, missing samples may be more consequential if their absence is related to concentration, tolerability, illness, or group membership. No missing-data assumptions or imputation procedures are reported in the registry record. It is therefore not possible to determine whether incomplete sampling could have affected the estimates.
What does over-dispersion mean in general?
Over-dispersion means the observed variability is greater than a model’s assumed variability. It is a concern in some count-data or regression settings, where an overly restrictive variance assumption can make uncertainty look too small. It is not a result reported for this pharmacokinetic endpoint. For positive exposure measurements, the pertinent issues would instead include the distribution of values, relative variability, and adequacy of the chosen summary and model. The record reports a geometric mean and geometric coefficient of variation as endpoint summary measures, but does not report model diagnostics or distribution checks.
Overall, the registry identifies a non-compartmental exposure endpoint and a pharmacokinetic-evaluable population. It does not provide enough analysis detail to assess estimator behavior, model assumptions, missing-data sensitivity, or uncertainty in group contrasts. Those limits prevent an independent statistical assessment of the primary pharmacokinetic findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary pharmacokinetic endpoint and multiple secondary pharmacokinetic outcomes. The secondary outcomes cover concentration, timing, clearance, half-life, residence time, distribution volume, and additional AUC measures. Considering multiple endpoints can increase the chance of a chance-positive finding if many hypothesis tests are conducted. In general, multiplicity procedures may control that risk, or analyses may be treated as descriptive; which approach was used cannot be determined from the endpoint list alone.
A multiplicity adjustment, prespecified hierarchy, or distinction between confirmatory and exploratory tests is not reported in the registry record. The number of listed outcome measures is 35, and the record lists 4 analyses, but it does not explain how those measures and analyses were organized for inference. It is not reported whether all were tested, whether tests were adjusted, or how any competing results would have been interpreted.
The primary endpoint population requires intended dose and concentration-time data adequate for parameter estimation. The number of enrolled participants is 46, but the number with an evaluable primary endpoint is not reported in the registry record. Missing concentration samples, reasons for missingness, exclusions from analysis, and any imputation or sensitivity analyses are also not reported. These details matter because a complete-profile analysis can represent a different set of participants from the enrolled group.
The registry record does not report a detailed statistical analysis plan, interim analyses, or a trial-specific sample-size justification. A planning illustration based on an observed effect is not equivalent to the trial’s design justification or observed power. Without the prespecified testing strategy, population counts, and missing-data handling, the scope of confirmatory inference cannot be established from the registry record.
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 Hepatic Function | 3 | 11 | 27.3% |
| Mild Hepatic Impairment | 10 | 17 | 58.8% |
| Moderate Hepatic Impairment | 8 | 14 | 57.1% |
| Severe Hepatic Impairment | 4 | 4 | 100.0% |
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 Hepatic Function | 10 of 11 |
| Mild Hepatic Impairment | 17 of 17 |
| Moderate Hepatic Impairment | 14 of 14 |
| Severe Hepatic Impairment | 3 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|---|
| Ascites | Gastrointestinal disorders | 0 of 11 | 0 of 17 | 3 of 14 | 0 of 4 |
| Sepsis | Infections and infestations | 1 of 11 | 1 of 17 | 1 of 14 | 0 of 4 |
| Acute kidney injury | Renal and urinary disorders | 0 of 11 | 0 of 17 | 1 of 14 | 2 of 4 |
| Anaemia | Blood and lymphatic system disorders | 0 of 11 | 1 of 17 | 1 of 14 | 0 of 4 |
| Lower respiratory tract infection | Infections and infestations | 1 of 11 | 1 of 17 | 0 of 14 | 0 of 4 |
| Pneumonia | Infections and infestations | 1 of 11 | 1 of 17 | 0 of 14 | 0 of 4 |
| Blood bilirubin increased | Investigations | 0 of 11 | 0 of 17 | 2 of 14 | 0 of 4 |
| Hepatic encephalopathy | Nervous system disorders | 0 of 11 | 0 of 17 | 0 of 14 | 2 of 4 |
| Splenic vein occlusion | Blood and lymphatic system disorders | 0 of 11 | 1 of 17 | 0 of 14 | 0 of 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 11 | 0 of 17 | 1 of 14 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Hepatic Function | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment |
|---|---|---|---|---|---|
| Fatigue | General disorders | 8 of 11 | 7 of 17 | 8 of 14 | 0 of 4 |
| Anaemia | Blood and lymphatic system disorders | 6 of 11 | 10 of 17 | 3 of 14 | 2 of 4 |
| Diarrhoea | Gastrointestinal disorders | 4 of 11 | 4 of 17 | 4 of 14 | 1 of 4 |
| Nausea | Gastrointestinal disorders | 3 of 11 | 5 of 17 | 5 of 14 | 0 of 4 |
| Oedema peripheral | General disorders | 4 of 11 | 2 of 17 | 5 of 14 | 0 of 4 |
| Constipation | Gastrointestinal disorders | 1 of 11 | 5 of 17 | 4 of 14 | 0 of 4 |
| Alanine aminotransferase increased | Investigations | 1 of 11 | 5 of 17 | 4 of 14 | 0 of 4 |
| Blood bilirubin increased | Investigations | 0 of 11 | 1 of 17 | 9 of 14 | 0 of 4 |
| Decreased appetite | Metabolism and nutrition disorders | 3 of 11 | 5 of 17 | 2 of 14 | 0 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 11 | 4 of 17 | 3 of 14 | 0 of 4 |
Serious events with the highest arm-level rate: hepatic encephalopathy (50.0%), acute kidney injury (50.0%), multi-organ failure (25.0%), acute hepatic failure (25.0%), bacterial sepsis (25.0%).
The registry reports safety counts separately for each hepatic-function group. For serious adverse events, the listed at-risk and affected counts are 11 and 3 for normal hepatic function, 17 and 10 for mild hepatic impairment, 14 and 8 for moderate hepatic impairment, and 4 and 4 for severe hepatic impairment. For other adverse events, the corresponding at-risk and affected counts are 11 and 10, 17 and 17, 14 and 14, and 4 and 3.
These are participant counts as recorded for the study’s safety groups. They should not be read as a randomized comparison or as evidence that hepatic-function category caused a safety difference. Group sizes differ, and the study has no separate control arm. The registry record does not give exposure-adjusted event rates, time-to-event estimates, or a controlled estimate of risk.
Selected serious adverse event terms are listed with percentages: hepatic encephalopathy and acute kidney injury, 50.0% each; multi-organ failure, acute hepatic failure, bacterial sepsis, and septic shock, 25.0% each. The record does not clarify the denominator for these term percentages in the information, so they should be read as reported, not recalculated or assigned a denominator.
Deaths are not reported in the registry record. The safety counts describe observed events in this study and do not, on their own, establish comparative safety or predict outcomes in other populations.
12. What the Result Does, and Does Not, Mean
The registry record shows that a Phase 1 study was organized to characterize carfilzomib pharmacokinetics and safety among participants assigned to hepatic-function categories. Its primary endpoint was exposure, measured as AUC0-last after carfilzomib 27 mg/m² on cycle 1 day 16. The record also identifies the pharmacokinetic-evaluable population and lists several additional pharmacokinetic outcomes.
However, the numerical primary endpoint findings are not reported in the registry record. There are no group-specific AUC0-last estimates, measures of dispersion, confidence intervals, or formal comparison results in the record. Consequently, the record does not allow readers to judge whether measured exposure was higher or lower across groups, how large any difference was, or how precisely it was estimated. No conclusion about efficacy can be drawn from the primary endpoint because it is pharmacokinetic rather than an efficacy measure, and efficacy results are not reported in the registry record.
The study’s non-randomized, single-arm design also defines what group comparisons could mean. The hepatic-function groups did not result from random assignment, and there was no untreated or active-control group. Any observed contrast would describe differences between the groups as enrolled; it could not, without suitable design and analysis assumptions, isolate the effect of hepatic impairment from other differences between participants.
The safety counts provide a descriptive record of participants with serious and other adverse events in each group. They do not establish that one group had a higher causal risk, and the safety information does not include a randomized control comparison. Death counts and the analysis details needed to interpret the serious-event term percentages are not reported in the registry record.
Thus, the registry record is useful for understanding the study’s design, endpoint definitions, and recorded safety counts. It is not sufficient to quantify pharmacokinetic differences, assess their precision, or make a causal or efficacy claim. Those conclusions would require numerical outcome results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between describing a pharmacokinetic question and reporting its statistical answer. The endpoint is clearly specified: exposure from infusion start to the last measured concentration, calculated from individual profiles using a non-compartmental approach. The record also defines the population whose data were intended to support the estimates. Yet without the numerical estimates and uncertainty measures, the central statistical comparison cannot be evaluated.
The group structure also illustrates why design labels matter. Hepatic-function categories may be useful for organizing pharmacokinetic assessment, but they are not randomized treatment arms. The presence of four groups does not create a controlled experiment, and group contrasts do not automatically support causal conclusions. Statistical interpretation must reflect the non-randomized, single-arm design.
The registry further highlights the difference between enrollment and endpoint evaluability. Participants need adequate concentration-time data for pharmacokinetic estimation, so the analysis population may be smaller than the enrolled population. Reporting participant flow and group-specific evaluable counts would help readers understand how much information supports each estimate and whether exclusions might affect comparability.
Finally, the record distinguishes a primary pharmacokinetic outcome from other registered measures and safety outcomes. A well-defined primary endpoint does not by itself reveal how multiple outcomes were handled, how uncertainty was quantified, or whether analyses were prespecified. These details are needed to assess the strength and scope of statistical claims. The trial is therefore a useful example of why complete outcome reporting and transparent analysis methods are essential alongside a precise endpoint definition.
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 most consequential limitation in the registry record is the absence of numerical results for the primary pharmacokinetic endpoint. Group-specific estimates, dispersion values, confidence intervals, and formal tests are not reported in the registry record. The listed secondary pharmacokinetic outcomes likewise lack numerical results in the information, limiting assessment of the broader concentration profile.
The study is non-randomized and single-arm, with hepatic-function groups rather than a separate control arm. The record does not report adjustment methods or enough participant characteristics to assess potential differences between groups. Consequently, observed contrasts would be vulnerable to confounding and should not be interpreted as causal effects of hepatic impairment.
The enrollment is 46, while group-specific counts for the pharmacokinetic-evaluable population are not reported in the registry record. The endpoint depends on receiving the intended dose and having usable concentration-time data, so the number analyzed may differ from enrollment. Reasons for missing samples, exclusions, and their distribution across groups are not reported.
The arm descriptions are truncated, which limits interpretation of dosing and treatment continuation details. The record also does not report the full statistical analysis plan, multiplicity procedures, interim analyses, sample-size justification, or sensitivity analyses. Safety counts are descriptive, and the denominator for the selected serious-event term percentages is not clarified in the record. Death counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment — NCT01949545.
- Registry record last updated 2017-05-02; status last verified 2017-04.
- Results first posted 2016-10-21.
- 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
NCT01949545 is a completed, open-label, non-randomized, single-arm Phase 1 study sponsored by Amgen. It enrolled 46 participants with advanced malignancies and grouped them by normal, mild, moderate, or severe hepatic function. The recorded study start is 2013-10, and primary completion is 2015-08.
Participants received intravenous carfilzomib. The primary endpoint was AUC0-last for 27 mg/m² on cycle 1 day 16, estimated from individual concentration-time profiles using a non-compartmental approach. The primary population required intended dose and evaluable pharmacokinetic data.
The registry reports safety counts by group but does not report numerical results for the primary pharmacokinetic endpoint, the detailed analysis plan, or the sample-size justification. Because the groups were not randomized and no separate control arm was included, group comparisons are descriptive rather than like-for-like treatment comparisons.