A Study to Understand the Effect of a Study Medicine Called ARV-471 on Rosuvastatin in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Understand the Effect of a Study Medicine Called ARV-471 on Rosuvastatin in Healthy Adults (NCT05652660), a na phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) of Rosuvastatin.

2. Clinical Question

The study was designed to examine a pharmacokinetic interaction in healthy adults, not to compare clinical outcomes or assess treatment of a disease. Rosuvastatin is described in the study summary as a BCRP substrate. The central question is whether exposure to rosuvastatin, as represented by its maximum measured plasma concentration, changes under the two dosing conditions. The record does not report an estimate of the size or precision of any change, so the direction and magnitude of the pharmacokinetic result cannot be established from the registry information.

3. Trial Design

This was a Phase 1, interventional, open-label, fixed-sequence study with a crossover model. The registry record lists 12 participants, a healthy population, and a completed status. All participants received rosuvastatin alone in Period 1 and ARV-471 followed by rosuvastatin in Period 2. ARV-471 was given 90 minutes before rosuvastatin in Period 2. The study summary says participants stayed at the clinic for 10 days and 9 nights.

The crossover structure means each participant contributed observations under both dosing conditions. Such a design can make a within-person comparison informative because each participant serves as their own comparator. However, this study did not randomize the treatment order: the rosuvastatin-alone period always came first, followed by the combination period. The registry lists allocation as not applicable and masking as none. Consequently, treatment condition is linked to period, and the record does not describe a randomized or blinded comparison.

The registry record does not report dose amounts, a washout interval, or further details about the timing between periods. Those details should not be inferred from the fixed-sequence description or the clinic stay. The primary outcome was rosuvastatin Cmax, with blood sampling planned at predose and at specified post-dose times through 72 hours on Day 1 of each period. The study also lists safety outcomes involving adverse events, laboratory results, electrocardiograms, and vital signs. The registry record does not report a statistical analysis plan or explain how the different outcome measures were handled analytically.

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 study consisted of 2 Periods in a single fixed sequence. A total of 12 participants were enrolled in the study and received study intervention.

Period 1 (5 Days)

Period 2 (4 Days)

Analysis population for the primary outcome, as defined in the registry: All participants enrolled and who took at least 1 dose of study intervention and had at least 1 PK parameter of interest.

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 baseline analysis population defined as all participants enrolled and who took at least 1 dose of study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) of Rosuvastatin, measured over 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72 hours post dose on Day 1 in Periods 1 and 2.

The primary endpoint was the maximum plasma concentration of rosuvastatin, abbreviated Cmax and measured in nanograms per milliliter. Cmax is the highest concentration observed in plasma over the sampling period. The record says it was observed directly from the data, rather than calculated from a fitted concentration curve. Samples were scheduled at predose and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours after dosing on Day 1 in each period.

In pharmacokinetic studies, Cmax is used to describe the peak concentration reached after a dose. Comparing Cmax under different dosing conditions can help characterize whether one medicine is associated with a change in the measured peak concentration of another. This is a pharmacokinetic measure, not by itself a measure of clinical benefit or harm.

The registry record specifies that the endpoint is summarized as a geometric mean, with geometric coefficient of variation as the dispersion measure. These summaries describe concentration data on a multiplicative scale and their relative variability. However, the record does not report the Cmax summaries, the comparison estimate, or its uncertainty. Therefore, the endpoint definition is available, but the numerical primary result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the study as open-label, fixed-sequence, and crossover. These design terms shape how a treatment comparison should be read. They do not, by themselves, specify the statistical model used to analyze the observations. The registry record does not report that model, the treatment-effect estimate, or an uncertainty interval for the primary outcome.

What does a crossover comparison mean?

In a crossover study, participants receive more than one treatment condition, so outcomes can be compared within the same participant. A within-person comparison can account for characteristics that remain relatively stable for that person during the study. The design assigns rosuvastatin alone to Period 1 and ARV-471 followed by rosuvastatin to Period 2 for every participant. The record therefore describes a fixed sequence, not a randomized sequence.

Because the treatment condition changes at the same time as the study period, a difference between periods cannot automatically be attributed only to the medicines. General methodological concerns in a fixed-sequence design include period effects, such as changes over time, and possible carryover from an earlier condition. Whether these concerns were relevant, and how they were addressed, is not reported in the registry record. The record also does not report a washout interval, so none should be assumed.

Why report a geometric mean?

Concentration measurements often vary multiplicatively: a given proportional change can be more meaningful than a fixed absolute change across the range of observed values. A geometric mean is calculated using logarithms and then expressed back on the original scale. It can summarize a positively valued, right-skewed measure such as a plasma concentration. The registry record specifies geometric means for Cmax and geometric coefficient of variation for dispersion, but does not provide the numerical summaries.

Geometric coefficient of variation describes relative variability around a geometric mean. It is not the same as a standard deviation expressed in the original measurement units. Greater relative variability generally means less precision in estimating a group summary when other conditions are similar. The actual variability and precision in this study cannot be assessed from the endpoint definition alone.

What would an uncertainty interval tell the reader?

In general, a confidence interval describes the range of estimates compatible with the observed data under the statistical method used. Its width reflects statistical precision: a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. An interval for a pharmacokinetic comparison would help readers assess both the estimated change and the range of values consistent with the data. The registry record does not report such an interval for the primary endpoint. No interval or treatment comparison should therefore be inferred.

A p-value, when reported, addresses compatibility between the data and a specified null hypothesis under the analysis assumptions. It does not measure the size or clinical importance of an effect. No p-value for the primary comparison is reported in the registry record. The absence of a reported p-value does not establish that the conditions were equal or different.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when outcome variability exceeds what an assumed statistical model allows. If a model underestimates variability, its uncertainty estimates may be too small and its intervals may be too narrow. Model choice should account for the type and distribution of the endpoint. Cmax is a continuous pharmacokinetic measure, and the record specifies geometric summaries, but does not report the model or variance assumptions used for inference. Over-dispersion is not documented as a finding in this study.

The study description also lists safety outcomes as participant counts, which are different from the continuous Cmax endpoint. General methods for event counts depend on how events are defined, whether participants can contribute more than one event, and the analysis question. The registry record reports participant counts for selected safety categories, but does not provide a detailed inferential method for those outcomes.

What do the planning assumptions establish?

The registry record describes sample-size illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial was originally designed using those assumptions. The record does not report the trial’s own sample-size justification. Nor does it provide the numerical planning results in the registry record described for this analysis. Such illustrations cannot substitute for the observed treatment estimate and its uncertainty.

Overall, the design and endpoint details support an explanation of what the study set out to measure. They do not reveal which analysis was performed or what the primary estimate was. The statistical analysis plan, including any model adjustments or handling of period effects, is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists six outcome measures and two analyses, but does not report how the analyses correspond to those outcomes or whether any multiplicity adjustment was planned. When several outcomes or comparisons are examined, multiplicity can increase the chance of observing an apparently notable result by chance. General approaches include defining one primary comparison in advance, adjusting statistical thresholds, or interpreting secondary findings as exploratory. Which approach was used in this study is not reported in the registry record. The primary endpoint is identified as rosuvastatin Cmax, but that designation alone does not establish how other analyses were handled.

The record defines the primary endpoint population as all participants enrolled who took at least one dose of study intervention and had at least one pharmacokinetic parameter of interest. It does not report the number included in the primary analysis, whether any participants lacked usable measurements, or how missing samples or incomplete concentration profiles were handled. The record also does not report whether participants were excluded from any analysis or how deviations from the planned sampling schedule were treated.

Missing-data methods matter because the reason data are unavailable can affect interpretation. For example, missingness related to a participant’s condition or measured outcome may have different implications from a missed sample unrelated to the outcome. These are general considerations; the registry record does not describe the pattern or reasons for missing data. The analysis population for the safety counts is reflected by the 12 participants at risk in each period, but further analysis-population details are not reported. No assumptions about missingness or imputation should be inferred.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports serious adverse events for 12 participants at risk in each period. No serious adverse events were reported in Period 1 with rosuvastatin alone, and none were reported in Period 2 with ARV-471 plus rosuvastatin. The record also reports zero deaths in both periods. No serious-event terms are listed.

For other adverse events, one participant was reported as affected in Period 1 and three participants in Period 2. These are participant counts, not a measure of event severity, duration, or causal relationship. The record does not describe the specific other events in the information available, nor does it report whether events resolved or required action.

Because the same participants passed through both periods in a fixed order, the period counts are not results from independent, randomized groups. Counts should not be treated as a like-for-like randomized safety comparison. The registry record does not establish that any event was caused by ARV-471 or rosuvastatin, and the counts alone do not determine whether the safety profiles differ. They describe reported events in this small study cohort only.

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

This study’s statistical purpose was to characterize rosuvastatin pharmacokinetics under two dosing conditions: rosuvastatin alone and rosuvastatin after ARV-471. The primary measure was Cmax, the maximum observed plasma concentration. A crossover structure allowed each participant to undergo both conditions, but the order was fixed, with the rosuvastatin-alone period first. The registry record therefore describes a within-participant comparison whose treatment conditions are also linked to study period.

The registry record does not report the primary Cmax summaries or a numerical comparison between conditions. It therefore does not establish whether Cmax was higher, lower, or similar after ARV-471, nor how precisely any difference was estimated. The endpoint definition and sampling schedule explain what was measured, but they are not results. No conclusion about the size or statistical uncertainty of the pharmacokinetic effect can be drawn from the information reported.

The safety information is similarly limited. The record reports no serious adverse events or deaths in either period, and reports one participant with another adverse event in Period 1 and three in Period 2. These figures do not identify event types or establish causality. They are descriptive counts from a study of healthy adults, not a basis for conclusions about safety in other populations.

The study does not answer a clinical efficacy question. It evaluates a pharmacokinetic measure and reports selected safety counts. It should not be read as evidence that either medicine benefits or fails to benefit people with a medical condition. Generalizing beyond the healthy participants or the conditions tested would require evidence not contained in the registry record. The most accurate interpretation is that the study’s objective and design are documented, while the primary numerical result and key analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

Pharmacokinetic interaction studies ask whether exposure to one medicine changes when another is given. That question is distinct from whether a medicine improves a clinical outcome. By naming rosuvastatin Cmax as the primary endpoint and specifying repeated post-dose sampling in both periods, the registry record makes clear that the focus was measured drug concentration rather than a disease outcome.

The crossover design is statistically relevant because participants contribute observations under both conditions. In general, this can make comparisons less affected by stable between-person differences. At the same time, the fixed sequence ties treatment condition to period. That feature matters when considering whether a measured contrast could also reflect time or other period-related influences. The record’s description of a fixed order should therefore be kept in view when interpreting the design.

The reporting gap is also important for statistical interpretation. The endpoint is defined, but the record does not report its numerical results, the treatment comparison, or an uncertainty interval. Without those, readers cannot judge the magnitude or precision of a pharmacokinetic difference. A well-described outcome definition cannot replace the estimate itself.

Finally, the reported adverse-event counts illustrate why descriptive safety information should be separated from an inferential comparison. The two periods involve the same participants in a fixed order, and the record supplies limited detail about event types. The figures document reported counts, but do not establish cause or comparative risk. Together, these features make the study useful for understanding how a Phase 1 interaction question is structured, while also showing why design, analysis reporting, and outcome estimates are all needed for a complete statistical interpretation.

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 interpretation is that the registry record does not report the numerical Cmax results or a comparison estimate. No confidence interval or p-value for the primary outcome is reported either. As a result, the direction, magnitude, and precision of the main pharmacokinetic finding cannot be evaluated.

The study enrolled 12 healthy participants, limiting how much can be learned about variability across broader populations. The registry record does not provide participant characteristics beyond the healthy status, so the cohort cannot be described further. This Phase 1 study was designed around pharmacokinetics, and its findings should not be treated as clinical outcome evidence.

The fixed sequence is a design-specific limitation. All participants received rosuvastatin alone first and the combination condition second. Treatment condition is therefore confounded with period, unlike a randomized sequence that balances order. The record does not report how possible period effects were evaluated. It also does not report a washout interval, so the potential relevance of carryover cannot be assessed from the registry information.

The open-label design means masking was absent. The primary endpoint is a concentration measurement, but the registry record does not report laboratory procedures or other safeguards that might inform measurement interpretation. It also does not report the statistical model, handling of missing samples, analysis of period effects, multiplicity procedures, or the trial’s own sample-size justification. Safety reporting includes counts but not the types of other adverse events or detailed causal assessments. These omissions constrain interpretation; they do not show that any particular bias or problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Understand the Effect of a Study Medicine Called ARV-471 on Rosuvastatin in Healthy Adults — NCT05652660.
• Registry record last updated 2024-07-26; status last verified 2024-02.
• Results first posted 2024-07-26.
• 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

The registry record describes a completed Phase 1, interventional, open-label, fixed-sequence crossover study in healthy adults, with 12 participants enrolled. Participants received rosuvastatin alone in Period 1 and ARV-471 90 minutes before rosuvastatin in Period 2. The primary endpoint was rosuvastatin maximum plasma concentration, summarized as a geometric mean with geometric coefficient of variation.

The record reports no serious adverse events or deaths in either period. It reports one participant with another adverse event in Period 1 and three in Period 2. It does not report numerical primary pharmacokinetic results, a treatment comparison, or an uncertainty interval. Details of the statistical analysis plan, missing-data handling, and multiplicity procedures are not reported in the registry record.