Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants (NCT05045638), a non-randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin.

2. Clinical Question

The study focuses on whether rosuvastatin’s measured concentration in plasma differs when it is given alone versus with sotorasib. Its stated purpose also includes assessing rosuvastatin pharmacokinetics when administered alone. The registry identifies rosuvastatin as a breast cancer resistance protein substrate in the official study title, but the record does not report a mechanistic analysis or a clinical consequence of any pharmacokinetic change.

This question is addressed in healthy participants rather than in a patient population. The registry lists 13 participants enrolled, and describes measurements after rosuvastatin administration on Days 1 and 6. It does not report the primary endpoint estimates, the magnitude or direction of a difference, or a confidence interval. Accordingly, the record establishes the study question and how the endpoint was defined, but not the numerical answer to that question.

3. Trial Design

This was a Phase I, open-label, fixed-sequence crossover study, with non-randomized allocation. The registry lists the study as completed and gives an enrollment of 13. The study dates recorded are 2021-08-20 for the start and 2021-10-10 for primary completion. The sponsor was Amgen.

A crossover design measures participants under more than one treatment condition, so a participant can contribute data under rosuvastatin alone and under rosuvastatin coadministered with sotorasib. The registry lists those two conditions and describes rosuvastatin pharmacokinetic sampling on Days 1 and 6. It does not report the treatment sequence in enough detail to establish which condition came first, how long any interval between conditions lasted, or whether participants completed both conditions. Those details are not reported in the registry record.

Fixed sequence means the treatment order was not randomized, and the registry explicitly identifies allocation as non-randomized. The record also specifies no masking. Thus, this was not a blinded randomized comparison. Its crossover structure is relevant to interpretation because measurements from the same participant may be related, but the statistical model used to account for that relationship is not reported in the registry record.

The registry identifies the study population as healthy participants. Its primary pharmacokinetic population included participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable pharmacokinetic data. The record does not describe how many enrolled participants contributed evaluable primary endpoint data or whether anyone withdrew or was excluded. The protocol’s sample-size justification is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The participants received 10 mg rosuvastatin on Day 1 and 960 mg sotorasib coadministered with 10 mg rosuvastatin on Day 6.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.

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 1 dose of sotorasib or rosuvastatin and had at least 1 postdose safety assessment.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin, measured over Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6.

The primary endpoint is the maximum observed plasma concentration of rosuvastatin, abbreviated Cmax, measured in ng/mL. It represents the highest measured plasma concentration in the sampling period and is one way to describe the peak of a drug’s concentration profile. The registry states that the primary parameter is a geometric mean, with geometric coefficient of variation as the measure of dispersion.

In general, pharmacokinetic endpoints describe how drug concentrations change over time after administration. Cmax is useful when the question concerns peak exposure, while other pharmacokinetic measures can characterize exposure across a longer interval. In this study, Cmax was used to assess rosuvastatin after administration alone and after coadministration with sotorasib. The study also lists other pharmacokinetic outcomes, including measures for sotorasib, but the primary question centers on rosuvastatin Cmax.

The recorded sampling schedule spans predose (Hour 0) and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose, following rosuvastatin administration on Days 1 and 6. The registry says pharmacokinetic parameters were determined using standard non-compartmental methods. It does not report the numerical Cmax estimates, a comparison estimate, or its uncertainty, so the endpoint definition alone cannot indicate the size or direction of any difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a pharmacokinetic analysis based on standard non-compartmental methods. It identifies Cmax as the primary endpoint, with geometric mean as the summary parameter and geometric coefficient of variation as the dispersion measure. It does not report the detailed statistical model, transformations, comparison estimate, confidence interval method, or hypothesis test used for the primary comparison. Those analysis details are not reported in the registry record.

What does Cmax measure?

Cmax is the largest observed concentration in a series of plasma measurements after a dose. It is called an observed maximum because it is selected from measurements taken at specified sampling times. In general, the observed maximum can depend on the timing and density of those samples: a true peak occurring between collection times may not be captured exactly. The registry lists sampling from predose through 120 hours postdose and describes the same schedule following rosuvastatin administration on Days 1 and 6.

Cmax is different from an area-under-the-curve measure, which summarizes concentration over time. The study lists Cmax as the primary measure for rosuvastatin, while the secondary outcomes include pharmacokinetic measures for sotorasib. The record does not report the values of these outcomes.

Why report a geometric mean?

A geometric mean summarizes positive measurements by taking their multiplicative rather than additive center. In general, this can be appropriate for pharmacokinetic measurements when proportional differences are more meaningful than fixed absolute differences, and when values have a right-skewed distribution. The geometric coefficient of variation describes relative variability around that geometric mean. Neither summary should be mistaken for a comparison between treatment conditions: the geometric mean describes a group’s concentration distribution, while a treatment comparison requires an estimate contrasting conditions.

The registry specifies these summary measures but does not report whether the primary comparison was expressed as a ratio, how any estimate was calculated, or what uncertainty interval accompanied it. A confidence interval, in general, gives a range of values compatible with the data and analysis under its assumptions. Its width indicates precision; it does not by itself establish clinical importance. No confidence interval for the primary endpoint is reported in the registry record.

What does non-compartmental analysis mean?

Non-compartmental pharmacokinetic methods summarize observed concentration-time data without requiring the data to be represented by a specified number of model compartments. In general, these methods use the observed concentration profile and time points to derive pharmacokinetic parameters. The registry states that standard non-compartmental methods were used, but does not specify software, calculation details, handling of concentrations below quantification limits, or derivation rules for each parameter.

How does the crossover structure affect analysis?

In a crossover study, participants may contribute measurements under multiple conditions. In general, comparisons can account for the fact that repeated measurements from the same person are related. A fixed sequence is not randomized, however, so the treatment condition is linked to the order in which it is received. Period effects, sequence effects, or carryover can matter in crossover settings. These are general design considerations, not evidence that any such effect occurred in this trial. The registry does not report a model for within-participant data, a period or sequence analysis, or an assessment of carryover.

The study is marked non-randomized and unmasked, and the registry warns that the arms are not a like-for-like control comparison. The crossover format should therefore not be described as a randomized trial. The record does not report whether treatment-period differences were adjusted for or how the fixed sequence was accounted for statistically.

What can planning calculations tell a reader?

A planning illustration based on an observed effect is not the same as the trial’s original design justification, and it is not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% power or other stated power levels; time-to-event illustrations use a total event count. These calculations are conditional on their assumptions and are not evidence that the trial had a particular probability of detecting an effect. The protocol’s own sample-size justification is not reported in the registry record.

The registry records seven outcome measures and three analyses. Their existence does not establish how the primary endpoint was tested, whether estimates were adjusted, or how uncertainty was calculated. Those procedures are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and three analyses. It identifies rosuvastatin Cmax as the primary outcome and lists secondary outcomes that include the number of participants reporting any treatment-emergent adverse events and Cmax, AUClast, and AUCinf of sotorasib. The registry record does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for multiple statistical tests. It is therefore not possible to determine from the record whether any reported statistical tests were intended to control the chance of false-positive findings across multiple outcomes.

Missing-data procedures are also not reported in the registry record. The pharmacokinetic population is defined as participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable pharmacokinetic data. This definition describes who could be included in that population, but does not say how many participants had evaluable primary endpoint data, why any data might have been unavailable, or how incomplete concentration profiles were handled. Rules for exclusions, imputation, or sensitivity analyses are not reported.

The record does not describe the statistical analysis population for every outcome. It does not state whether every enrolled participant was included in the safety summaries, although the safety counts list 13 at risk in each of the two conditions. The analysis plan, including any interim analyses, is not reported in the registry record. Without those details, the number of planned tests, the treatment of missing values, and the relationship between analysis populations cannot be fully assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The safety figures list 13 participants at risk in the rosuvastatin condition and 13 at risk in the sotorasib plus rosuvastatin condition. The recorded number affected is zero for serious adverse events in each condition and zero for the other adverse-event category in each condition. The death count is also zero in both groups.

These are counts from the registry’s posted safety summaries. The record also lists the number of participants reporting any treatment-emergent adverse events as a secondary outcome, but does not provide a numerical result for that outcome in the information available. The terms used in the safety summary should not be taken to provide a complete description of every event, its timing, severity, duration, or relationship to study treatment. Those details are not reported in the registry record.

In general, a zero count means no affected participants are recorded in that category for the listed group; it does not establish that the event is impossible or that the same pattern would occur in a larger or different population. The study enrolled healthy participants, and the safety counts alone do not answer the pharmacokinetic question about rosuvastatin Cmax.

12. What the Result Does, and Does Not, Mean

The study was designed to measure rosuvastatin pharmacokinetics when rosuvastatin was given alone and when coadministered with sotorasib. The primary endpoint, maximum observed plasma concentration, is relevant to the stated pharmacokinetic question. The registry identifies the measurement schedule, the geometric-mean summary, and the use of non-compartmental methods. It does not report the numerical primary endpoint results or the estimated contrast between conditions.

Without those estimates, the record cannot establish whether Cmax was higher, lower, or similar across the two conditions, or how precisely any difference was measured. It also cannot establish the statistical significance of a comparison. The absence of reported estimates is not evidence that the conditions had identical concentrations; it means the numerical comparison is not reported in the registry record.

Even with a reported pharmacokinetic contrast, interpretation would need to distinguish statistical evidence from clinical importance. In general, an estimate describes the size and direction of a difference, while its uncertainty describes how precisely it is known. The clinical implications of a concentration difference require additional context and evidence. This study enrolled healthy participants and measured a pharmacokinetic endpoint, rather than a patient-centered clinical outcome.

The design was non-randomized, open-label, and fixed sequence. These features are important when considering the strength of any comparison; the registry itself cautions that the arms are not a like-for-like control comparison. The record does not describe how treatment order or other period-related considerations were handled analytically.

The safety counts record zero affected participants in the serious and other adverse-event categories for both listed conditions, with zero deaths. They do not establish safety beyond the participants and categories recorded. The results should therefore be read as a description of the study’s registered design and posted counts, not as a broad conclusion about treatment effects or clinical outcomes.

13. Why This Trial Matters Statistically

This study is statistically useful as an example of a focused pharmacokinetic question addressed with a crossover design. The same participants may contribute measurements under rosuvastatin alone and in combination with sotorasib, which can support within-participant comparisons. The study’s fixed sequence and non-randomized allocation also illustrate why a crossover design should not automatically be treated as randomized: treatment condition and period order may be linked.

The endpoint clarifies what the study set out to measure. Cmax captures the maximum observed plasma concentration, while geometric means and geometric coefficients of variation summarize concentration data on a multiplicative scale. These choices are common statistical concepts in pharmacokinetic analysis, but a reader still needs the contrast estimate and its uncertainty to judge the data’s implications. Those results are not reported in the registry record.

The record also makes clear that study design and outcome reporting are separate kinds of information. It describes the population, treatment conditions, sampling schedule, and pharmacokinetic population definition. It does not report the primary estimate, a confidence interval, the detailed analysis model, or missing-data procedures. As a result, the design can be described more fully than the statistical evidence for the primary comparison.

Finally, the safety counts provide a compact view of recorded affected-participant counts, but do not substitute for detailed event reporting or the pharmacokinetic analysis. The trial’s healthy-participant setting, modest enrollment of 13, and non-randomized fixed sequence all help define the scope of what the record can establish. Clear reporting of estimates, uncertainty, and analysis methods would be needed to assess the primary comparison more completely.

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 central limitation for interpreting the primary question is that the registry record does not report the Cmax estimates or a comparison between rosuvastatin alone and rosuvastatin with sotorasib. It also does not report an uncertainty interval or statistical test. Consequently, the size, direction, and precision of the primary comparison cannot be assessed from the record.

The study enrolled 13 participants and involved healthy participants. This defines a small, specific study population; the record does not report how many of those enrolled had evaluable primary endpoint data. The registered pharmacokinetic population requires dose receipt and evaluable pharmacokinetic data, but the number meeting that definition is not reported.

The design was open-label, non-randomized, and fixed sequence. The registry cautions that the arms are not a like-for-like control comparison. It does not report details of treatment order, the interval between conditions, or statistical handling of period, sequence, or carryover considerations. These are relevant features of a crossover design, but the record does not establish that any particular bias occurred.

The registry states that standard non-compartmental methods were used, but does not describe the statistical model, data transformations, treatment of incomplete data, or multiplicity approach. Missing-data rules and interim analyses are not reported. The protocol’s sample-size justification is also not reported in the registry record.

These limitations concern what can be concluded from the registry record. They do not establish that the study lacked methods or results outside that record; they mean those details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants — NCT05045638.
• Registry record last updated 2023-08-14; status last verified 2022-10.
• Results first posted 2023-08-14.
• 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.

18. Record Summary

NCT05045638 is a completed Phase I, open-label, fixed-sequence crossover study sponsored by Amgen. It enrolled 13 healthy participants and examined rosuvastatin administered alone and with sotorasib. Allocation was non-randomized.

The primary endpoint was rosuvastatin maximum observed plasma concentration, summarized as a geometric mean with geometric coefficient of variation. Sampling was scheduled from predose through 120 hours following rosuvastatin administration on Days 1 and 6; pharmacokinetic parameters were determined using standard non-compartmental methods.

The registry record does not report the primary endpoint estimates, their uncertainty, detailed statistical analysis methods, missing-data procedures, or multiplicity strategy. Safety summaries list zero affected participants for serious and other adverse-event categories in each condition, and zero deaths.