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 Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma (NCT01454076), a randomized phase 1 study. The primary outcome is Cmax: Maximum Observed Plasma Concentration for Ixazomib.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01454076 |
| Phase | Phase 1 |
| Condition | Nonhematologic Malignancies, Lymphoma |
| Allocation | Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 112 |
| Arms in the primary outcome | 8 |
| Lead sponsor | Millennium Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced nonhematologic malignancies or lymphoma. The primary pharmacokinetic endpoint used a defined PK-evaluable population: participants who received the specified Cycle 1 dose without dose reductions or interruptions, avoided excluded concomitant medication during PK sampling, and had enough concentration-time data for estimation.
Intervention
Oral ixazomib was assessed in five arms. The study examined ixazomib with ketoconazole, two ixazomib capsule formulations, fasted and fed administration, ixazomib with rifampin, and ixazomib with clarithromycin. Doses and schedules varied across arms.
Comparator
There was no single comparator across the study. The arm structure included within-arm conditions such as ixazomib alone and with a concomitant drug, Capsule A and Capsule B, and fasted and fed dosing. The registry describes the study as randomized and sequential, but does not report a single common comparison.
Primary question
What maximum observed plasma concentration of ixazomib was measured in the PK-evaluable participants under the different study conditions? This is a pharmacokinetic question about peak concentration, rather than a direct test of clinical benefit or a single treatment-versus-control effect.
The registry lists the study as a phase 1 investigation in participants with advanced nonhematologic malignancies or lymphoma. Its stated aims included relative bioavailability, food effect, and drug-drug interaction assessments, alongside safety and tolerability. The primary endpoint was maximum observed plasma concentration, reported as a geometric mean with standard deviation.
Because the arms cover different conditions and do not constitute one uniform comparison, the results need to be read condition by condition. They do not amount to a single estimate of ixazomib versus a common control.
3. Trial Design
The registry describes an open-label, multicenter, randomized, sequential, five-arm, phase 1 study. Enrollment was 112, and the study status is completed. The recorded start date is 2011-11-10, and primary completion is recorded as 2015-04-01. The sponsor is Millennium Pharmaceuticals, Inc.
The five arms addressed different pharmacokinetic questions. Arm 1 assessed ixazomib 2.5 mg with ketoconazole 400 mg and included an ixazomib-alone condition. Arm 2 compared Capsule A and Capsule B at ixazomib 4 mg. Arm 3 assessed ixazomib 4 mg in fasted and fed conditions. Arm 4 assessed ixazomib 4 mg with rifampin 600 mg, and Arm 5 assessed ixazomib 2.5 mg with clarithromycin 500 mg. The registry describes dosing schedules that included single doses on specified study days, with subsequent ixazomib treatment in some arms.
Randomization is reported, but the registry record does not report the randomization procedure, sequence generation, allocation concealment, or assignment ratios. It identifies the study model as sequential but does not describe how participants moved through the study conditions or whether the sequence was randomized within each arm. The masking field is none, consistent with the open-label description.
The posted primary endpoint summaries have different participant counts by condition: 16 in each of the two Arm 1 conditions; 14 in each Arm 2 capsule condition; 15 in each Arm 3 food condition; 16 in the Arm 4 combination condition; and 15 in the Arm 5 combination condition. These are the reported PK summary counts, not the overall enrollment. The record does not explain the difference between enrollment and the counts contributing to each primary endpoint summary.
The design is suited to examining measured pharmacokinetic quantities under several conditions, but the registry does not present these arms as a single head-to-head efficacy trial. The study’s overall enrollment should therefore not be interpreted as the sample size for one common comparison.
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 advanced nonhematologic malignancies or lymphoma were enrolled in this 5 arm study to receive one of the following treatments in Cycle 1: ixazomib + ketoconazole; ixazomib Capsule A or B formulation; ixazomib in fasted or fed state; ixazomib + rifampin; ixazomib + clarithromycin; Cycle 2 up to Cycle 12: ixazomib alone in all arms.
Overall Study
| Stage | Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | Arm 2: Ixazomib 4 mg Capsule A or B | Arm 3: Ixazomib 4 mg Fasted or Fed | Arm 4: Ixazomib 4 mg + Rifampin 600 mg | Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg |
|---|---|---|---|---|---|
| STARTED | 29 | 20 | 24 | 18 | 21 |
| COMPLETED | 16 | 14 | 15 | 16 | 15 |
| NOT COMPLETED | 13 | 6 | 9 | 2 | 6 |
Reasons for not completing this period:
| Reason | Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | Arm 2: Ixazomib 4 mg Capsule A or B | Arm 3: Ixazomib 4 mg Fasted or Fed | Arm 4: Ixazomib 4 mg + Rifampin 600 mg | Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg |
|---|---|---|---|---|---|
| Other | 2 | 0 | 0 | 1 | 2 |
| Withdrawal by Subject | 3 | 4 | 2 | 1 | 2 |
| Adverse Event | 8 | 2 | 7 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK)-evaluable population included all participants who received protocol-specified dose in Cycle 1 without dose reductions/interruptions, did not receive any excluded concomitant medication during PK sampling, and had sufficient concentration-time data to permit 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 population included all participants who received at least one dose of any study drug.
| Characteristic | Unit | Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | Arm 2: Ixazomib 4 mg Capsule A or B | Arm 3: Ixazomib 4 mg Fasted or Fed | Arm 4: Ixazomib 4 mg + Rifampin 600 mg | Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 29 | 20 | 24 | 18 | 21 | 112 | |
| Age, Continuous | years | 61.8 (SD 8.71) | 60.5 (SD 13.33) | 62.3 (SD 11.86) | 61.6 (SD 11.33) | 60.0 (SD 11.04) | 61.3 (SD 11.01) |
| Sex: Female, Male: Female | Participants | 17 | 11 | 11 | 8 | 6 | 53 |
| Sex: Female, Male: Male | Participants | 12 | 9 | 13 | 10 | 15 | 59 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 5 | 3 | 1 | 4 | 16 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 26 | 15 | 21 | 17 | 17 | 96 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 | 2 | 4 | 0 | 0 | 11 |
| Race (NIH/OMB): White | Participants | 22 | 15 | 18 | 17 | 19 | 91 |
| Race (NIH/OMB): More than one race | Participants | 1 | 1 | 1 | 0 | 1 | 4 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 2 | 1 | 0 | 0 | 4 |
| Region of Enrollment: United States | participants | 29 | 20 | 24 | 18 | 21 | 112 |
| Height | centimeter (cm) | 166.6 (SD 9.26) | 166.4 (SD 9.64) | 170.2 (SD 9.76) | 169.2 (SD 10.03) | 172.6 (SD 11.11) | 168.9 (SD 10.00) |
| Weight | kilogram (kg) | 77.44 (SD 19.956) | 69.78 (SD 13.057) | 74.09 (SD 16.358) | 80.22 (SD 17.183) | 81.93 (SD 20.973) | 76.64 (SD 18.083) |
6. Primary Endpoint
The registry lists the primary outcome as Cmax: Maximum Observed Plasma Concentration for Ixazomib, measured over Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Deviation |
| Unit | nanogram per milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is Cmax, defined as the maximum observed plasma concentration of ixazomib, measured in nanograms per milliliter (ng/mL). The registry reports a geometric mean and standard deviation for each condition. Sampling occurred before dosing and at multiple post-dose time points; the stated observation windows differed by arm, extending up to 264 hours in Arms 1 and 5, up to 216 hours in Arms 2 and 3, and up to 168 hours in Arm 4.
General statistical context: Cmax describes the observed peak concentration during the sampling period. It is used in pharmacokinetic studies because peak concentration can help characterize how drug exposure changes with formulation, food, or coadministered drugs. It is one feature of a concentration-time profile, not a complete description of exposure. Other pharmacokinetic quantities may describe exposure over time, but they are not the primary endpoint reported in these results.
A geometric mean summarizes positive measurements on a multiplicative scale and can be useful when pharmacokinetic values are skewed. The reported standard deviation describes dispersion, but the record does not provide confidence intervals for the endpoint summaries. Cmax alone does not establish clinical benefit, toxicity, or the clinical importance of a difference between conditions.
The endpoint population was restricted to participants with protocol-specified dosing and sufficient eligible concentration-time data. It is therefore not necessarily identical to all enrolled participants. The registry’s PK-evaluable criteria define who contributed to this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted summaries describe peak ixazomib concentrations under several distinct conditions. In Arm 1, the geometric mean Cmax was 38.98 ng/mL for ixazomib 2.5 mg alone and 39.25 ng/mL with ketoconazole 400 mg; each summary included 16 participants. For Arm 2, the geometric means were 61.87 ng/mL for Capsule A and 71.95 ng/mL for Capsule B, with 14 participants in each condition. In Arm 3, the geometric mean was 77.0 ng/mL in the fasted condition and 22.75 ng/mL in the fed condition, with 15 participants in each condition.
For Arm 4, the geometric mean was 25.71 ng/mL for ixazomib 4 mg with rifampin 600 mg, based on 16 participants. For Arm 5, the geometric mean was 37.24 ng/mL for ixazomib 2.5 mg with clarithromycin 500 mg, based on 15 participants. These are descriptive summaries. The registry record does not report confidence intervals, hypothesis tests, or adjusted comparisons for these Cmax results, so the summaries alone do not establish whether observed differences exceed sampling variability.
The reported standard deviations also indicate variation in the participant-level measurements. They are 21.37 and 27.33 for the two Arm 1 conditions; 48.39 and 46.21 for the Arm 2 capsule conditions; and 53.59 and 15.05 for the Arm 3 food conditions. The standard deviation is 15.14 for the Arm 4 combination condition and 21.44 for the Arm 5 combination condition. Since the record gives no confidence intervals, these dispersion measures should not be treated as a substitute for uncertainty intervals around the geometric means.
The registry’s stated aims include drug interaction and relative bioavailability assessments, but the numerical results do not cover every component of those aims in a directly comparable way. For example, a single ixazomib-alone condition is not listed alongside the Arm 4 rifampin and Arm 5 clarithromycin conditions in the posted primary summaries. Differences across separate arms may reflect differences in participants or study conditions as well as the condition of interest. The sequential design and absence of a common comparator matter when interpreting across-arm contrasts.
The registry lists four secondary outcome topics: treatment-emergent adverse events and serious adverse events, clinically significant laboratory abnormalities related to treatment-emergent adverse events, clinically significant vital-sign abnormalities, and best overall response. Numerical results for these secondary outcomes are not reported in the registry record. Safety counts are separately posted; they do not supply the missing numerical results for all secondary outcomes.
Overall, the results support a descriptive reading of measured peak concentrations within the specified conditions and PK-evaluable population. Without inferential estimates and fuller details of the analysis, the posted summaries do not quantify precision for between-condition effects or establish that any observed difference is attributable to the condition being assessed.
9. Statistical Methods Explained
The primary endpoint is a continuous pharmacokinetic measure, Cmax, and the registry reports a geometric mean and standard deviation for each listed condition. General statistical context: a geometric mean is calculated on a logarithmic scale and transformed back to the original measurement scale. It is often used for positive measurements with right-skewed distributions, which can occur in concentration data. The registry does not report the transformation details or the distributional checks used for this analysis.
What does the standard deviation describe?
General statistical context: a standard deviation describes how dispersed individual measurements are around a mean, in the units of the measurement. Here, the posted standard deviation accompanies each geometric mean, but the record does not explain the precise calculation convention used alongside the geometric mean. It does not by itself provide the uncertainty of the estimated geometric mean. A confidence interval would give a range of values compatible with an estimation procedure and its assumptions; no confidence interval is reported for these endpoint summaries.
The PK-evaluable population excludes participants who did not meet the stated dosing, concomitant-medication, or concentration-time-data criteria. Such criteria can make pharmacokinetic estimates interpretable for participants with usable sampling, but the record does not state how many participants were excluded from each arm or why. The full analysis plan, rules for missing concentration measurements, and handling of concentrations below assay limits are not reported in the registry record.
Why do the arms need separate interpretation?
The five arms concern different questions and do not share one comparator. Some listed conditions form a within-arm contrast, such as Capsule A versus Capsule B or fasted versus fed administration. Other conditions include concomitant drugs. The record does not provide a single common comparison across all five arms, nor does it report inferential contrasts for every condition. Comparing the numerical summaries across arms as if they came from one randomized comparison could be misleading, especially when participant composition and sampling schedules can differ.
General statistical context: randomization can reduce systematic differences between groups when the allocation process is properly implemented. A registry entry that identifies a trial as randomized does not, on its own, describe the sequence-generation method, concealment, stratification, or how randomization was used for each within-arm condition. Those details are not reported in the registry record.
What do the sample-size illustrations mean?
General statistical context: a planning illustration estimates the number of participants that might be required under specified assumptions to detect a chosen effect. The stated assumptions for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. These are planning assumptions, not the original trial’s design justification. The registry record does not report the trial’s own sample-size justification.
Any such planning estimate is conditional on its assumed effect and statistical model. It is not observed power and does not describe the probability that the completed trial detected an effect. In particular, the registry does not report inferential results for the primary endpoint, and no planning number can replace an interval estimate or hypothesis test from the actual analysis. No numerical planning estimates are reported in the registry record.
What does over-dispersion mean in general?
General statistical context: over-dispersion occurs when observed variation is greater than a statistical model assumes. If an analysis ignores excess variation, standard errors can be too small and confidence intervals too narrow. This matters particularly for count outcomes such as adverse-event counts. The posted primary endpoint is a concentration measure, and the registry provides standard deviations, but it does not report a model-based analysis that assesses over-dispersion. No claim about over-dispersion in this study can be made from the posted summaries alone.
The record identifies zero posted inferential analyses for the primary outcome. It does not state a statistical testing framework, adjustment method, confidence-interval procedure, or model specification. Accordingly, the most defensible statistical reading is descriptive: the reported geometric means and standard deviations summarize the eligible participants’ observed Cmax measurements under each listed condition.
10. Multiplicity, Missing Data and Analysis Populations
The study has multiple pharmacokinetic questions across five arms, as well as several safety and response outcomes. When many outcomes or comparisons are tested, the chance of a false-positive finding can increase unless the analysis plan addresses multiplicity. General statistical context: multiplicity procedures can control the overall error rate or organize which comparisons are confirmatory. The registry record does not report whether any multiplicity adjustment was planned or used, or which comparisons, if any, were considered primary beyond the stated Cmax endpoint.
No inferential analyses are posted for the primary endpoint, and numerical results for the listed secondary outcome topics are not reported in the registry record. Consequently, there are no reported p-values or confidence intervals with which to assess statistical uncertainty or the handling of multiple comparisons. The record also does not report whether interim analyses occurred.
Missing-data handling is not reported in the registry record. The primary endpoint’s PK-evaluable definition specifies sufficient concentration-time data and other eligibility criteria, but there is no arm-by-arm account of participants omitted from the endpoint summaries, missing sampling times, or reasons for missingness. General statistical context: excluding participants with incomplete measurements may be reasonable for some pharmacokinetic summaries, but the implications depend on why measurements are absent and whether exclusions are related to the outcome.
The population used for the Cmax summaries is explicitly the PK-evaluable population. The record does not report a separate intention-to-treat analysis or other analysis populations for the safety and response outcomes. The absence of these details limits assessment of selection, missingness, and the comparability of analysis populations across endpoints.
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 |
|---|---|---|---|
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 12 | 29 | 41.4% |
| Arm 2: Ixazomib 4 mg Capsule A or B | 5 | 20 | 25.0% |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 12 | 24 | 50.0% |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 3 | 18 | 16.7% |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 10 | 21 | 47.6% |
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 |
|---|---|
| Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | 28 of 29 |
| Arm 2: Ixazomib 4 mg Capsule A or B | 20 of 20 |
| Arm 3: Ixazomib 4 mg Fasted or Fed | 23 of 24 |
| Arm 4: Ixazomib 4 mg + Rifampin 600 mg | 18 of 18 |
| Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg | 20 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | Arm 2: Ixazomib 4 mg Capsule A or B | Arm 3: Ixazomib 4 mg Fasted or Fed | Arm 4: Ixazomib 4 mg + Rifampin 600 mg | Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg |
|---|---|---|---|---|---|---|
| Dehydration | Metabolism and nutrition disorders | 3 of 29 | 0 of 20 | 2 of 24 | 0 of 18 | 0 of 21 |
| Colitis | Gastrointestinal disorders | 1 of 29 | 1 of 20 | 0 of 24 | 0 of 18 | 0 of 21 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 29 | 2 of 20 | 0 of 24 | 0 of 18 | 0 of 21 |
| Abdominal pain | Gastrointestinal disorders | 1 of 29 | 0 of 20 | 1 of 24 | 0 of 18 | 0 of 21 |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 29 | 0 of 20 | 2 of 24 | 0 of 18 | 0 of 21 |
| Pyrexia | General disorders | 1 of 29 | 0 of 20 | 1 of 24 | 0 of 18 | 0 of 21 |
| Syncope | Nervous system disorders | 0 of 29 | 0 of 20 | 0 of 24 | 1 of 18 | 1 of 21 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 29 | 0 of 20 | 0 of 24 | 1 of 18 | 0 of 21 |
| Mental status changes | Psychiatric disorders | 0 of 29 | 0 of 20 | 1 of 24 | 0 of 18 | 1 of 21 |
| Acute kidney injury | Renal and urinary disorders | 1 of 29 | 0 of 20 | 1 of 24 | 0 of 18 | 0 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg | Arm 2: Ixazomib 4 mg Capsule A or B | Arm 3: Ixazomib 4 mg Fasted or Fed | Arm 4: Ixazomib 4 mg + Rifampin 600 mg | Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg |
|---|---|---|---|---|---|---|
| Fatigue | General disorders | 20 of 29 | 7 of 20 | 9 of 24 | 8 of 18 | 8 of 21 |
| Decreased appetite | Metabolism and nutrition disorders | 13 of 29 | 7 of 20 | 6 of 24 | 4 of 18 | 5 of 21 |
| Asthenia | General disorders | 11 of 29 | 4 of 20 | 5 of 24 | 1 of 18 | 2 of 21 |
| Anaemia | Blood and lymphatic system disorders | 7 of 29 | 4 of 20 | 6 of 24 | 0 of 18 | 1 of 21 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 29 | 3 of 20 | 4 of 24 | 2 of 18 | 5 of 21 |
| Weight decreased | Investigations | 2 of 29 | 2 of 20 | 6 of 24 | 2 of 18 | 3 of 21 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 29 | 2 of 20 | 5 of 24 | 2 of 18 | 4 of 21 |
| Chills | General disorders | 5 of 29 | 2 of 20 | 2 of 24 | 2 of 18 | 1 of 21 |
| Anxiety | Psychiatric disorders | 5 of 29 | 2 of 20 | 2 of 24 | 0 of 18 | 2 of 21 |
| Thrombocytopenia | Blood and lymphatic system disorders | 6 of 29 | 2 of 20 | 2 of 24 | 1 of 18 | 0 of 21 |
Serious events with the highest arm-level rate: dehydration (10.3%), small intestinal obstruction (10.0%), endometrial cancer (8.3%), non-cardiac chest pain (5.6%), syncope (5.6%).
The registry posts counts of participants with one or more serious adverse events and counts with other treatment-emergent adverse events across the five arms. In Arm 1, 12 of 29 participants had a serious adverse event and 28 of 29 had other treatment-emergent adverse events. The corresponding counts were 5 of 20 and 20 of 20 in Arm 2; 12 of 24 and 23 of 24 in Arm 3; 3 of 18 and 18 of 18 in Arm 4; and 10 of 21 and 20 of 21 in Arm 5.
These are participant counts, not event totals, and each arm has a different at-risk count. The arms also involve different conditions, so these numbers should not be read as a randomized comparison of safety between one treatment and a common control. The registry does not report deaths for these groups; death figures are not reported in the registry record.
The record lists serious-event terms with percentages, including dehydration at 10.3%, small intestinal obstruction at 10.0%, endometrial cancer at 8.3%, non-cardiac chest pain at 5.6%, syncope at 5.6%, and back pain at 5.6%. The denominator and exact tabulation basis for those percentages are not reported in the registry record. These terms do not establish causation by ixazomib or another study drug.
12. What the Result Does, and Does Not, Mean
The posted results describe pharmacokinetic measurements and selected safety counts in a phase 1 study of oral ixazomib. The primary endpoint, Cmax, concerns peak plasma concentration, and the summaries show the measured geometric means and standard deviations for each listed study condition. The study’s aims included investigating formulation, food, and coadministered-drug conditions.
These data do not answer a single clinical efficacy question. The endpoint is pharmacokinetic rather than a direct measure of tumor response, survival, or quality of life. Although best overall response is listed as a secondary outcome, numerical results for it are not reported in the registry record. The posted concentration summaries do not show whether any condition improves clinical outcomes.
The numerical summaries also do not establish that a difference between two conditions is statistically reliable or clinically important. No confidence intervals or inferential tests are reported. Some conditions occur in different arms, and the registry does not provide one shared comparator for the full set of questions. Cross-arm differences therefore should not automatically be attributed to the differing formulation, food condition, or coadministered drug.
The safety counts describe participants who experienced events, but do not by themselves establish that study treatment caused those events. The record does not provide complete numerical results for all listed safety outcomes, and the arm structures do not form a single common safety comparison. Serious-event terms and their percentages also require caution because their denominator is not reported.
In general, pharmacokinetic studies can help characterize how drug concentrations vary across conditions. They do not alone determine whether a treatment is appropriate for an individual or demonstrate a clinical benefit. The registry record is most informative as a descriptive account of Cmax and selected safety counts in its specified study populations.
13. Why This Trial Matters Statistically
This study illustrates why pharmacokinetic trial results need to be interpreted in relation to the question each arm addresses. Formulation, food, and coadministered-drug conditions are distinct sources of variation in drug concentration. A sequential multi-arm design can address several such questions within one study, but the resulting summaries do not necessarily form a single coherent treatment comparison.
Reporting a geometric mean alongside a standard deviation conveys both a typical concentration summary and observed variability. At the same time, readers need uncertainty estimates and clearly defined comparisons to assess how precisely condition-specific differences have been estimated. Those inferential details are not reported for the posted primary results. This makes the distinction between descriptive measurement and evidence from a formal comparison especially important.
The study also demonstrates the importance of analysis-population definitions. The primary endpoint uses a PK-evaluable population defined by dosing, medication restrictions, and availability of concentration-time data. That definition indicates that endpoint summaries depend on eligibility for pharmacokinetic assessment rather than simply overall enrollment.
Finally, the record places pharmacokinetic summaries alongside safety information, but these answer different questions. Cmax characterizes a peak concentration; adverse-event counts describe events among participants. Neither type of result should be mistaken for a comprehensive assessment of clinical efficacy or a causal safety comparison. The limits of the posted analyses are part of the interpretation, not a reason to overstate what descriptive results establish.
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 study has multiple arms addressing different pharmacokinetic conditions, with no single common comparator across all arms. This limits interpretation of broad cross-arm contrasts. The registry reports that the study was randomized and sequential, but does not describe the randomization procedure, sequence allocation, or how the design supports each specific comparison.
The primary endpoint summaries are limited to the PK-evaluable population. The registry defines this population but does not report the number or reasons for participants excluded from each summary. The observation windows differ across arms, and the full concentration sampling schedule and assay details are not reported in the registry record.
The registry posts geometric means and standard deviations, but no confidence intervals, hypothesis tests, or adjusted comparisons for Cmax. It does not report the statistical model, transformations, multiplicity approach, or the original sample-size justification. Therefore, the summaries cannot quantify uncertainty for between-condition effects or establish a statistically supported difference.
The four secondary outcomes are listed, but numerical results are not reported in the registry record. The safety counts provide information on participants with events, but the record does not provide death figures or the denominator for the listed serious-event percentages. These limitations leave important details about safety, response, missingness, and the relationship between posted summaries and the full enrolled population unresolved.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma — NCT01454076.
- Registry record last updated 2017-11-01; status last verified 2017-06.
- Results first posted 2017-11-01.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, open-label, multicenter, randomized, sequential phase 1 study of oral ixazomib in participants with advanced nonhematologic malignancies or lymphoma. Enrollment was 112. Five arms assessed ketoconazole, capsule formulation, food conditions, rifampin, and clarithromycin.
The primary endpoint was maximum observed plasma concentration of ixazomib, reported as a geometric mean with standard deviation in a PK-evaluable population. Condition-specific summaries and participant counts are posted. The record also lists four secondary outcome topics and provides selected adverse-event counts.
No inferential analyses are posted for the primary endpoint. Confidence intervals, statistical tests, multiplicity procedures, missing-data methods, and the trial’s sample-size justification are not reported in the registry record. The results therefore support descriptive interpretation of the posted concentrations and safety counts, rather than a single comparative conclusion.