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 Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction (NCT01912222), a non-randomized phase 1 study. The primary outcome is Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01912222 |
| Phase | Phase 1 |
| Condition | Advanced Solid Tumors, Hematologic Malignancies |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Millennium Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced solid tumors or hematologic malignancies, grouped by normal hepatic function, moderate hepatic impairment, or severe hepatic impairment. The registry describes liver-function categories as defined by the National Cancer Institute Organ Dysfunction Working Group.
Intervention
Oral ixazomib. In Part A, the normal-function group received a single 4 mg dose, the moderate-impairment group received a single 2.3 mg dose, and the severe-impairment group received a single 1.5 mg dose on Day 1.
Comparator
The groups differ in liver-function status and assigned dose. Allocation was nonrandomized, so these groups should not be treated as like-for-like randomized comparison arms. There is no separate placebo or untreated comparator described.
Primary question
How does unbound ixazomib exposure, measured by the area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, vary across the hepatic-function groups after the Part A dose?
The study was designed as a pharmacokinetic investigation, rather than as a trial testing a clinical outcome. The endpoint focuses on drug concentration over time, using measurements collected before dosing and at multiple post-dose timepoints through up to 336 hours. Its central question is whether exposure measurements differ across groups defined by hepatic function under the dosing conditions described in the registry record.
The registry lists 48 participants as the enrollment and identifies advanced solid tumors and hematologic malignancies as the conditions. It does not report results for the primary endpoint, so the direction and size of any observed exposure differences cannot be stated from the registry information. The nonrandomized allocation and different doses across groups also mean that any observed group contrast would need to be interpreted as a comparison of these study groups, not as an isolated causal effect of liver dysfunction.
3. Trial Design
This was a phase 1, two-part pharmacokinetic study with a parallel, nonrandomized design and no masking. It enrolled patients with advanced solid tumors or hematologic malignancies across categories of hepatic function. The registry lists enrollment of 48 and records the study as completed. The listed study start was 2013-08, and primary completion was 2015-03.
Part A involved a single oral dose of ixazomib on Day 1. The normal hepatic-function group received 4 mg, the moderate hepatic-impairment group received 2.3 mg, and the severe hepatic-impairment group received 1.5 mg. The registry descriptions say participants could continue from Part A into Part B, but the arm descriptions are truncated in the record. Further details of Part B are therefore not reported in the registry record available for this account.
Because assignment was nonrandomized, the three groups are not randomized treatment arms. They are defined by hepatic-function category and receive different doses. Differences in measured exposure could reflect the combination of group characteristics and dosing, as well as any other group differences; the registry does not establish that the groups were otherwise comparable. There is no basis in the record for treating one group as a randomized control for another.
The primary endpoint was assessed in the Part A pharmacokinetic analysis population. That population was defined as participants who received the single Part A dose, did not receive excluded concomitant medications through the end of pharmacokinetic sampling, and had sufficient concentration-time data for reliable pharmacokinetic estimation. The registry record does not report the number included in that population or the number contributing to each endpoint analysis.
The study lists six outcome measures, but the registry record does not provide a comparative analysis for the primary endpoint. The description therefore establishes the intended design and measurement framework, but not the results or the statistical procedures used to compare hepatic-function groups.
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 diagnosis of advanced solid tumors or hematologic malignancies having varying degrees of liver dysfunction enrolled in 1 of 3 treatment groups to receive ixazomib 4 mg (normal hepatic function), 2.3 mg (moderate impairment), 1.5 mg (severe impairment) on Day 1 (Part A, 15 day cycle) and on Days 1,8 and 15(Part B, 28 day cycle).
Part A: Pharmacokinetic Period
| Stage | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| STARTED | 13 | 15 | 20 |
| COMPLETED | 12 | 13 | 18 |
| NOT COMPLETED | 1 | 2 | 2 |
Reasons for not completing this period:
| Reason | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Not evaluable for PK analyses | 1 | 2 | 2 |
Part B: Treatment Period
| Stage | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| STARTED | 13 | 15 | 20 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 13 | 15 | 20 |
Reasons for not completing this period:
| Reason | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|
| Progressive disease | 10 | 12 | 15 |
| Adverse Event | 1 | 2 | 3 |
| Withdrawal by Subject | 2 | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: The PK analysis population was defined as participants who received the single dose of ixazomib in Part A of the study, did not receive any excluded concomitant medications through the completion of PK sampling, and had sufficient concentration-time data to permit the reliable estimation of PK parameters by noncompartmental analysis methods.
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.
Population: The safety analysis population was defined as participants who received at least 1 dose of ixazomib.
| Characteristic | Unit | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) | Total |
|---|---|---|---|---|---|
| Participants analysed | 13 | 15 | 20 | 48 | |
| Age, Continuous | years | 58.8 (SD 15.19) | 56.2 (SD 15.26) | 54.5 (SD 13.84) | 56.2 (SD 14.45) |
| Sex: Female, Male: Female | Participants | 7 | 7 | 6 | 20 |
| Sex: Female, Male: Male | Participants | 6 | 8 | 14 | 28 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 4 | 0 | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 10 | 9 | 20 | 39 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 3 | 2 | 0 | 5 |
| Race/Ethnicity, Customized: White | participants | 11 | 8 | 13 | 32 |
| Race/Ethnicity, Customized: Black or African American | participants | 2 | 2 | 6 | 10 |
| Race/Ethnicity, Customized: Other | participants | 0 | 4 | 0 | 4 |
| Race/Ethnicity, Customized: Asian | participants | 0 | 1 | 1 | 2 |
| Height | centimeter (cm) | 168.6 (SD 6.79) | 168.6 (SD 12.56) | 169.6 (SD 27.54) | 169.0 (SD 19.01) |
| Weight | kilogram (kg) | 74.42 (SD 16.788) | 76.97 (SD 12.050) | 76.94 (SD 23.498) | 76.27 (SD 18.431) |
| Disease type at diagnosis: Solid tumor | participants | 10 | 14 | 18 | 42 |
| Disease type at diagnosis: Other | participants | 3 | 1 | 2 | 6 |
| Months from initial diagnosis to first dose of ixazomib | months | 56.5 (SD 43.40) | 23.7 (SD 16.59) | 35.2 (SD 28.73) | 37.4 (SD 32.56) |
| Participants with prior antineoplastic therapy | participants | 13 | 15 | 20 | 48 |
| Participant with prior radiation: Had prior radiation | participants | 6 | 6 | 11 | 23 |
| Participant with prior radiation: Had no prior radiation | participants | 7 | 9 | 9 | 25 |
| Participant with prior surgery: Had prior surgery | participants | 12 | 14 | 18 | 44 |
| Participant with prior surgery: Had no prior surgery | participants | 1 | 1 | 2 | 4 |
| Baseline Eastern Cooperative Oncology Group (ECOG) performance status: 0 | participants | 1 | 0 | 1 | 2 |
| Baseline Eastern Cooperative Oncology Group (ECOG) performance status: 1 | participants | 12 | 15 | 19 | 46 |
| Baseline total bilirubin | micro mole per liter (mcmol/L) | 7.43 (SD 3.092) | 40.25 (SD 5.594) | 108.61 (SD 78.372) | 59.85 (SD 66.249) |
| Baseline aspartate aminotransferase (AST) | units per liter (U/L) | 21.04 (SD 6.884) | 169.97 (SD 147.433) | 197.48 (SD 198.211) | 141.09 (SD 167.256) |
6. Primary Endpoint
The registry lists the primary outcome as Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib, measured over Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Deviation |
| Unit | nanogram*hours per milliliter (ng*hr/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is unbound AUC(0-last), described as the unbound area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for ixazomib. It is expressed in nanogram*hours per milliliter (ng*hr/mL). The measurement uses concentration observations collected before dosing and at multiple timepoints after dosing, through up to 336 hours in Part A on Day 1.
AUC condenses a sequence of concentration measurements into a measure of exposure over a defined period. In general, a larger AUC represents greater measured drug exposure over that period, while the endpoint does not by itself describe clinical benefit, toxicity, or a patient’s response. Restricting the endpoint to unbound drug focuses on the portion not bound to plasma proteins. The registry does not provide further detail on how unbound concentrations were measured.
The endpoint is summarized as a geometric mean, with standard deviation identified as the dispersion measure. In general, a geometric mean is suited to positive measurements that may vary multiplicatively; it summarizes values on a logarithmic scale and then expresses the result on the original scale. A dispersion measure describes variability around the summary, but the registry record does not report the endpoint values, their standard deviations, or a confidence interval.
The endpoint is useful for characterizing pharmacokinetics across the hepatic-function groups. The registry record does not report the primary endpoint results, so it cannot support a statement about the magnitude or precision of any group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a study intended to characterize ixazomib exposure across groups with different levels of hepatic function. Its primary measure is unbound AUC(0-last), a pharmacokinetic summary of concentration over time. However, the primary endpoint result is not reported in the registry record. There is therefore no posted estimate, uncertainty interval, or statistical test result from which to describe the observed exposure pattern.
The study’s structure matters for interpreting any group comparison. Allocation was nonrandomized, the groups were based on hepatic-function status, and the assigned doses differed: 4 mg for normal hepatic function, 2.3 mg for moderate impairment, and 1.5 mg for severe impairment. A contrast among these groups is not equivalent to a randomized comparison in which treatment assignment is the only planned difference. The registry record does not establish that any observed contrast would be attributable solely to hepatic function.
The endpoint is based on concentration-time data, not a clinical outcome. Even if exposure estimates were available, they would not by themselves establish a clinical effect or characterize the balance of benefits and harms. The registry record contains adverse-event counts and selected serious-event terms, but it does not report a comparative analysis connecting those events with the primary pharmacokinetic endpoint.
Precision cannot be assessed for the primary endpoint because the registry record does not report its group estimates, standard deviations, confidence intervals, or analysis population counts. The planned enrollment is listed as 48, but the record does not provide the number analyzed for this endpoint. Planned enrollment and analysis sample size are not interchangeable: participants may not contribute usable pharmacokinetic data if eligibility for the analysis population is not met.
The posted record lists no comparative analyses for the outcome measures. Thus, no sponsor-reported inferential result for the primary endpoint can be described from the registry information. This is distinct from evidence that groups were equal or that no difference existed; the endpoint result is simply not reported in the registry record. The absence of a reported estimate also prevents assessment of whether any difference, if observed, was precise or clinically meaningful.
Any sample-size figures appearing with the posted calculations are planning illustrations based on an observed effect and stated assumptions, rather than the trial’s own design justification or observed power. They should not be read as results or as proof that the study could or could not detect a particular difference. The registry record does not report the study’s sample-size justification.
Overall, the record establishes the study question, the nonrandomized group structure, the Part A doses, and the intended pharmacokinetic endpoint. It does not establish the primary outcome result, a formal between-group conclusion, or a causal effect of liver dysfunction on exposure.
9. Statistical Methods Explained
What does a pharmacokinetic endpoint measure?
General: Pharmacokinetics concerns how drug concentrations change over time in the body. A concentration-time profile is formed from measurements taken at multiple points after dosing. An area under that profile summarizes exposure across a specified time window. The endpoint in this study runs from time 0 through the last quantifiable concentration and is restricted to unbound ixazomib. It is not a direct measure of a clinical outcome.
The endpoint description specifies measurements before dosing and at multiple timepoints after dosing, through up to 336 hours. The registry does not list the individual sampling times or explain how concentrations below quantification were handled. Such details can matter because estimating an area requires a rule for connecting or modeling observed concentrations and addressing the end of the measurement interval. Those analytic details are not reported in the registry record.
Why use a geometric mean?
General: Pharmacokinetic measurements are positive quantities and may be distributed asymmetrically, with some observations much larger than others. A geometric mean summarizes the typical level by working on a logarithmic scale and transforming back. It can be useful when variation is multiplicative rather than additive. It should not be confused with an arithmetic mean, which averages values on their original scale.
The registry identifies the primary endpoint summary as a geometric mean and its dispersion as standard deviation. It does not state whether that standard deviation was calculated on the original or transformed scale, and it gives no endpoint estimates. The meaning and numerical size of the reported dispersion therefore cannot be assessed from this record.
How should between-group comparisons be understood?
General: A comparison of group summaries describes how the measurements differ in the observed groups. A confidence interval, when reported, describes uncertainty around an estimate under the analysis assumptions; it is not a guarantee that the true value lies within the interval. A statistical test addresses compatibility with a specified null model, but a p-value alone does not convey the magnitude or practical importance of a difference.
Here, the registry lists nonrandomized allocation and a parallel group structure. The groups correspond to hepatic-function categories and receive different doses. As a result, an observed contrast would combine the group definitions and dosing conditions. Randomization cannot be invoked to balance other factors, and a causal interpretation isolating liver function is not established by the design description.
No primary endpoint estimates, confidence intervals, or test results are reported in the registry record. The registry also lists no comparative analyses for the outcomes. Consequently, there is no reported inferential result to interpret, and no basis to characterize the statistical significance or precision of the primary comparison.
Why can over-dispersion matter?
General: Over-dispersion occurs when the observed variability is greater than a model assumes. If a method understates variability, its uncertainty estimates may be too narrow and tests may be too optimistic. If variability is modeled appropriately, uncertainty is more accurately reflected. This concept is relevant to many outcome models, but the registry does not identify an over-dispersion model or report evidence of over-dispersion for this pharmacokinetic endpoint. It would be inappropriate to claim that such a method was used.
What do the sample-size illustrations mean?
The posted planning illustrations are based on the observed effect and use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider an effect specified as a fraction of the observed effect. These are planning calculations, not the original study’s design justification and not observed power. For non-time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event calculations use total events. General: A planning calculation is conditional on its assumptions and target effect. It does not show that a study achieved that power, nor does it replace the actual estimate and its uncertainty.
The registry record does not report the sample-size justification used when the trial was designed. It also does not give the numerical primary endpoint effect needed to assess the planning illustrations independently. The illustrations should therefore be read only as conditional scenarios, not as evidence about the study result.
What information is missing for a full statistical assessment?
The registry record does not report the primary endpoint estimates, analysis-specific sample sizes, confidence intervals, hypothesis tests, missing-data handling, or a detailed statistical analysis plan. It does not identify an adjustment for multiplicity or explain whether any interim analyses were conducted. These omissions limit assessment of how the primary result was estimated and how its uncertainty was quantified. The available design description and endpoint definition remain informative, but they do not substitute for the analysis results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures, but it does not report a multiplicity strategy. Multiplicity arises when several outcomes, groups, or statistical tests are examined: considering more tests can increase the chance of a seemingly notable result occurring by chance. General approaches include prioritizing a primary endpoint, adjusting inference across a family of tests, or clearly identifying analyses as exploratory. The registry record does not say whether any such approach was planned or used.
The registry record does not list comparative analyses for the outcomes and does not report the primary endpoint result. It therefore provides no result set in which to assess how multiplicity was handled. No interim analyses or stopping rules are described; their conduct is not reported in the registry record.
The primary pharmacokinetic analysis population was defined by receipt of the Part A single dose, absence of excluded concomitant medications through completion of pharmacokinetic sampling, and sufficient concentration-time data for reliable estimation. This definition identifies the intended population for the pharmacokinetic assessment, but the record does not report how many participants met it or how many were analyzed in each group.
Missing-data methods are not reported in the registry record. In general, incomplete concentration-time profiles can affect the ability to estimate exposure, particularly when measurements needed to characterize the profile are absent. The registry definition excludes participants without sufficient data for reliable estimation, but it does not explain how insufficient profiles were determined, how individual missing samples were handled, or whether any sensitivity analyses were conducted.
The registry lists enrollment of 48, but that figure does not establish the endpoint analysis sample size. The numbers analyzed for the primary endpoint and any exclusions from analysis are not reported in the registry record. Without those details, the completeness of the pharmacokinetic data and the effect of exclusions cannot be evaluated.
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 (Ixazomib 4 mg) | 6 | 13 | 46.2% |
| Moderate Hepatic Impairment (Ixazomib 2.3 mg) | 10 | 15 | 66.7% |
| Severe Hepatic Impairment (Ixazomib 1.5 mg) | 15 | 20 | 75.0% |
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 (Ixazomib 4 mg) | 12 of 13 |
| Moderate Hepatic Impairment (Ixazomib 2.3 mg) | 14 of 15 |
| Severe Hepatic Impairment (Ixazomib 1.5 mg) | 17 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|---|
| Renal failure acute | Renal and urinary disorders | 0 of 13 | 1 of 15 | 6 of 20 |
| Nausea | Gastrointestinal disorders | 1 of 13 | 0 of 15 | 1 of 20 |
| Ascites | Gastrointestinal disorders | 0 of 13 | 1 of 15 | 1 of 20 |
| Peritoneal haemorrhage | Gastrointestinal disorders | 0 of 13 | 1 of 15 | 1 of 20 |
| Hepatic failure | Hepatobiliary disorders | 0 of 13 | 1 of 15 | 1 of 20 |
| Hyperbilirubinaemia | Hepatobiliary disorders | 0 of 13 | 1 of 15 | 1 of 20 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 0 of 15 | 1 of 20 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 13 | 2 of 15 | 0 of 20 |
| Mental status changes | Psychiatric disorders | 0 of 13 | 0 of 15 | 2 of 20 |
| Fall | Injury, poisoning and procedural complications | 1 of 13 | 0 of 15 | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Hepatic Function (Ixazomib 4 mg) | Moderate Hepatic Impairment (Ixazomib 2.3 mg) | Severe Hepatic Impairment (Ixazomib 1.5 mg) |
|---|---|---|---|---|
| Decreased appetite | Metabolism and nutrition disorders | 7 of 13 | 2 of 15 | 1 of 20 |
| Anaemia | Blood and lymphatic system disorders | 2 of 13 | 3 of 15 | 3 of 20 |
| Hyperkalaemia | Metabolism and nutrition disorders | 1 of 13 | 2 of 15 | 3 of 20 |
| Diarrhoea | Gastrointestinal disorders | 4 of 13 | 1 of 15 | 1 of 20 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 2 of 15 | 3 of 20 |
| Insomnia | Psychiatric disorders | 3 of 13 | 2 of 15 | 1 of 20 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 13 | 0 of 15 | 3 of 20 |
| Hyponatraemia | Metabolism and nutrition disorders | 2 of 13 | 1 of 15 | 1 of 20 |
| Constipation | Gastrointestinal disorders | 1 of 13 | 1 of 15 | 2 of 20 |
| Leukocytosis | Blood and lymphatic system disorders | 1 of 13 | 1 of 15 | 2 of 20 |
Serious events with the highest arm-level rate: renal failure acute (30.0%), pulmonary embolism (13.3%), dehydration (13.3%), mental status changes (10.0%), nausea (7.7%).
The registry reports serious adverse events by hepatic-function group and gives the number at risk and the number affected. In the normal hepatic-function group, 6 of 13 participants were reported as affected; in the moderate hepatic-impairment group, 10 of 15 were affected; and in the severe hepatic-impairment group, 15 of 20 were affected. These are group-level counts, not a randomized comparison. The groups had different hepatic-function status and different ixazomib doses.
The record also lists participants affected by other, non-serious adverse events: 12 of 13 in the normal-function group, 14 of 15 in the moderate-impairment group, and 17 of 20 in the severe-impairment group. These counts describe participants with events, not the total number of event episodes. They do not indicate how many events each participant experienced.
Selected serious adverse-event terms are listed with percentages: Renal failure acute (30.0%), Pulmonary embolism (13.3%), Dehydration (13.3%), Mental status changes (10.0%), Nausea (7.7%), and Vomiting (7.7%). The record does not explain the denominators or method underlying these term percentages, so they should not be converted into participant counts or interpreted as comparative risks.
Deaths are not reported in the registry record. The listed figures do not establish that an event was caused by ixazomib, and the nonrandomized groups do not support a like-for-like safety comparison.
12. What the Result Does, and Does Not, Mean
This record describes a phase 1 pharmacokinetic study of oral ixazomib in patients with advanced solid tumors or hematologic malignancies and varying hepatic function. It specifies a Part A single-dose regimen and identifies unbound AUC(0-last) as the primary endpoint. These details define the question and the measurement approach, but the registry record does not report the primary endpoint results.
Accordingly, the record does not show whether measured unbound exposure was higher, lower, or similar across the hepatic-function groups. It does not provide an effect estimate, uncertainty interval, or comparative test result. Absence of a result in the registry is not evidence that there was no difference; it means the difference cannot be evaluated from the registry information.
Even with exposure estimates, interpretation would need to account for the nonrandomized design and different doses across groups. A group contrast would describe the groups under their assigned study regimens, rather than isolate the effect of hepatic impairment alone. The registry does not report sufficient information to establish comparability of the groups or to attribute a contrast to a single factor.
The endpoint measures drug exposure, not tumor response, survival, symptom change, or another clinical outcome. It therefore cannot by itself answer whether a treatment benefits patients. Likewise, the adverse-event counts and selected terms provide descriptive safety information, but they do not establish causation or support a randomized comparison.
The study’s statistical contribution, as represented in the registry, is its focused pharmacokinetic question and defined endpoint population. A full interpretation of results would require the reported group estimates, analysis population counts, uncertainty measures, and methods for handling incomplete data and comparisons. Those details are not reported in the registry record.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates the distinction between a pharmacokinetic measurement and a clinical outcome. AUC summarizes concentration over time and can characterize exposure, but it is not itself evidence of clinical benefit or harm. Clear interpretation begins by matching the claim to what the endpoint measures.
It also highlights the importance of design when interpreting group contrasts. The study groups are defined by hepatic function, allocation is nonrandomized, and dose differs across groups. These features mean that a numerical difference, if reported, would not automatically identify the effect of hepatic function alone. The design description must shape the strength and type of any conclusion.
The endpoint definition also shows why analysis populations matter in pharmacokinetic research. Reliable estimation depends on concentration-time information, and the registry limits the primary analysis population to participants with sufficient data and without specified excluded concomitant medications through sampling completion. Without the number analyzed or details of exclusions, readers cannot assess how much of the enrolled group contributed to the endpoint.
Finally, the record demonstrates that a precise research question and endpoint do not replace a posted result. The primary endpoint is clearly described, yet estimates and uncertainty are not reported in the registry record. Statistical interpretation requires both a defined measure and its observed estimate, together with information about precision and analysis methods. In their absence, conclusions must remain limited to the study’s stated objective and design.
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 interpreting this trial is that the registry record does not report the primary endpoint results. There are no group estimates, confidence intervals, or comparative test results to assess. The number of participants included in the pharmacokinetic analysis is also not reported, despite the listed enrollment of 48.
The nonrandomized design limits between-group interpretation. Groups are defined by hepatic-function category and receive different doses, so a contrast would not isolate the effect of hepatic function from the dosing conditions or other possible group differences. The record does not report adjustment methods or establish group comparability.
The registry describes a two-part study, but the arm descriptions available in the record are truncated during their account of possible Part B continuation. Additional details about Part B are not reported in the registry record. Nor does the record provide a detailed statistical analysis plan, sample-size justification, multiplicity approach, interim-analysis information, missing-data procedures, or endpoint-specific analysis counts.
For the primary endpoint, the registry does not explain the methods for estimating AUC from concentration-time data or handling measurements that are incomplete or not quantifiable. It identifies the summary as a geometric mean and dispersion as standard deviation, but does not give the values or clarify the scale used for the dispersion.
The safety information is descriptive and does not establish event causation. The record does not report deaths, and the denominators underlying the listed serious-event term percentages are not explained. These limitations leave the available safety figures unsuitable for a causal or randomized comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction — NCT01912222.
- Registry record last updated 2016-06-02; status last verified 2016-02.
- Results first posted 2016-03-25.
- 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 NCT01912222, a completed phase 1, two-part pharmacokinetic study of oral ixazomib in patients with advanced solid tumors or hematologic malignancies and varying hepatic function. Listed enrollment is 48. Allocation was nonrandomized, masking was none, and the study used a parallel model.
In Part A, participants received a single Day 1 dose: 4 mg with normal hepatic function, 2.3 mg with moderate hepatic impairment, or 1.5 mg with severe hepatic impairment. The primary endpoint was unbound AUC(0-last), measured in nanogram*hours per milliliter (ng*hr/mL). The pharmacokinetic analysis population required receipt of the Part A dose, no specified excluded concomitant medications through sampling completion, and sufficient concentration-time data for reliable estimation.
The registry record does not report the primary endpoint results, comparative analyses, endpoint analysis counts, or detailed statistical procedures. It lists serious and other adverse-event counts by group and selected serious-event terms. The design and endpoint are described, but the record does not support a conclusion about differences in ixazomib exposure across the groups.