A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Participants.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Participants. (NCT06385119), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs)..

2. Clinical Question

3. Trial Design

This completed phase 1 study was randomized, open-label and crossover, with two parts and single-dose treatment conditions. The registry lists enrollment of 28 participants. Its brief summary describes healthy male and female participants aged 18 to 55. The sponsor was Fore Biotherapeutics. The recorded start date was 2024-04-24 and primary completion date was 2024-12-22.

Part A examined food effects on plixorafenib administered with cobicistat, the effect of cobicistat on plixorafenib, and safety when plixorafenib was taken alone or with cobicistat. The treatment descriptions include fasted plixorafenib alone, fasted plixorafenib with cobicistat, and plixorafenib with cobicistat after a high-fat, high-caloric meal.

Part B examined high-fat and low-fat meals versus fasting for plixorafenib alone, and a low-fat meal versus fasting for plixorafenib with cobicistat. Its treatment descriptions include plixorafenib alone in fasted, high-fat meal and low-fat meal conditions, as well as plixorafenib with cobicistat following a low-fat meal. Each listed plixorafenib treatment used 900 mg; cobicistat was listed at 150 mg.

A crossover design means participants receive more than one treatment condition, allowing comparisons that can account for differences between participants. The treatment order, period structure beyond the references in the registry, washout interval, and the number of participants assigned to each sequence are not reported in the registry record. Open-label means the study was not masked, as the registry lists masking as none.

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.

Only the first 6 of 10 groups are shown.

Overall Study

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs)., measured over First dose of Plixorafenib to day 19 (Treatment Period 3)..

The primary endpoint is the number of participants with at least one reported treatment-emergent adverse event (TEAE). The registry defines the timeframe as first dose of plixorafenib to day 19 (Treatment Period 3). This is a participant-level count: it concerns whether a participant experienced at least one qualifying event during the stated period, rather than the total number of events experienced by each participant.

Safety endpoints of this kind are used to describe adverse events arising during treatment and the observation period. They can show how many participants had reported events under the listed treatment conditions. A count alone does not convey the event’s severity, duration, clinical importance, or relationship to treatment; those details require additional event-level information.

The registry’s primary endpoint is a safety measure, while the stated central study objectives concern plixorafenib pharmacokinetics under different food and cobicistat conditions. The secondary outcomes listed concern cumulative plixorafenib excreted in urine and the percent of dose excreted in urine in 48 hours. Numerical results for pharmacokinetic measures and those secondary outcomes are not reported in the registry record. Therefore, the available counts do not answer the pharmacokinetic questions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design contribute?

In general, a crossover design exposes participants to multiple treatment conditions, so a comparison can use measurements from the same participant under different conditions. This can reduce the influence of stable differences between participants. It does not remove the need to account for treatment order, period effects, carryover from an earlier condition, or missing measurements. Which of these factors was addressed, and how, is not reported in the registry record. The registry identifies randomization and crossover, but does not give the sequence allocation or the statistical model.

What does the primary endpoint count?

The primary endpoint is the number of participants with at least one TEAE during the recorded period, from the first plixorafenib dose to day 19 (Treatment Period 3). This is a binary status for each participant: event reported or no event reported during the period. When summarized as counts, the measure describes how many participants met that definition. It does not count all recurrent events as separate participants, and it does not on its own describe event severity or duration. The registry does not report an inferential analysis for this endpoint.

Why distinguish descriptive counts from comparisons?

A count for each treatment condition is descriptive. To make a comparative statistical claim, an analysis would need to define the contrast and account appropriately for the design. For a crossover study, paired comparisons may be relevant in general, but the registry does not report whether such methods were used. It also does not report a treatment-effect estimate, uncertainty interval, or p-value for the safety endpoint. Consequently, the recorded counts should not be treated as a tested difference between conditions.

How should precision be understood?

Precision concerns how much uncertainty surrounds an estimate. In general, confidence intervals communicate that uncertainty, while a point estimate alone does not. No confidence intervals for the listed safety counts are reported in the registry record. The number at risk is 12 for each listed condition, but the registry does not provide an interval or a statistical model from which to assess uncertainty. No additional calculation is made from the counts.

What can sample-size planning illustrations say?

In general, sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions. The registry record does not report the trial’s own sample-size justification. The planning illustrations associated with the posted results are described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is framed as a stated fraction of the observed effect. Such illustrations are planning exercises, not observed power and not evidence that the study was designed around those assumptions. No numerical planning estimates are reported in the registry record.

For binary outcomes, planning also depends on event rates and the contrast being targeted. A small number of events can make estimates imprecise, but the exact precision depends on the method and comparison. The registry does not report a planning calculation for this primary endpoint, nor an analysis linking the event counts to a prespecified effect. The treatment-specific counts should therefore remain descriptive.

Why can multiplicity matter?

In general, evaluating several endpoints or treatment comparisons increases the chance that at least one result may appear unusual by chance if each is tested separately. Statistical plans may address this through a hierarchy, adjustment, or a clearly exploratory interpretation. The registry lists multiple objectives, treatment conditions and outcome measures, but a multiplicity strategy or prespecified testing hierarchy is not reported in the registry record. The absence of that information prevents determining whether any reported comparison was intended as confirmatory. No comparative tests are reported in the posted results described by this record.

Pharmacokinetic analyses often summarize measures such as exposure or concentration over time, but the particular measures, transformations, models and decision criteria for this study are not specified in the posted results. General descriptions of pharmacokinetic methods cannot substitute for the missing analysis details. The record supports explaining the design and endpoints, but not reconstructing unreported estimates or statistical tests.

10. Multiplicity, Missing Data and Analysis Populations

The study includes several related questions: food effects on plixorafenib alone and with cobicistat, the effect of cobicistat, safety, and urine excretion outcomes. Multiple treatment conditions and outcomes can create multiplicity: in general, the more comparisons tested, the more opportunity there is for chance findings. Trials may address this through a prespecified hierarchy, adjustment of significance thresholds, or by labeling analyses exploratory. A multiplicity strategy and a testing hierarchy are not reported in the registry record.

The record does not report the statistical analysis plan, the inferential tests for the primary endpoint, or any comparative analyses. It lists 12 outcome measures and 0 analyses. Therefore, there is no basis in the record to determine which comparisons were planned as primary, whether secondary outcomes were tested formally, or how multiplicity may have been handled.

Missing-data rules and analysis populations are also not reported in the registry record. It is not stated how participants with missing pharmacokinetic samples, incomplete treatment periods, or unavailable safety follow-up would be handled, nor whether analyses used all randomized participants or a defined subset. In general, these choices can affect interpretation, especially in crossover studies where incomplete periods may affect within-participant comparisons. The number enrolled does not by itself establish the analysis population for any outcome.

The registry does not report a sample-size justification or assumptions for the trial’s original design. Any planning illustrations based on observed effects should be treated as planning information rather than as evidence of observed power. Without the analysis plan, missing-data rules and population definitions, the posted counts are most appropriately read as descriptive registry results.

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.

Most frequent non-serious adverse event terms

The serious adverse event figures are 0 for each of the seven listed treatment conditions. The registry gives 12 participants at risk for each condition, and records 0 deaths for every condition. These figures are counts, not evidence that the risk is zero beyond the observed study data. The registry lists no serious adverse event terms.

The figures for other adverse events are separate from the serious-event counts. The registry reports 1 participant for Treatment 1, 1 for Treatment 2, 1 for Treatment 3, 2 for Treatment A, 3 for Treatment B, 4 for Treatment C and 1 for Treatment D. They should not be read as severity rankings or as proof of a treatment effect. Event descriptions, grades, duration and attribution are not reported in the registry record.

Because this is a crossover study, the same participant may have received more than one treatment condition. The condition-specific counts therefore should not be added to infer a number of unique participants across the study. The treatment sequence and participant-level overlap are not reported in the registry record. These safety counts are descriptive and do not provide a formal comparative assessment.

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

The record documents a phase 1 crossover study of single-dose plixorafenib under food and cobicistat conditions in healthy participants. The safety results list no serious adverse events and no deaths for the treatment conditions, alongside the reported counts of other adverse events. Those data describe the safety observations recorded in this study and timeframe.

The counts do not establish that a treatment is safe or unsafe, nor do they establish that differences across conditions are caused by food or cobicistat. The record does not provide event details, comparative estimates, confidence intervals or statistical tests. The available safety figures therefore have limited ability to characterize uncertainty or distinguish among treatment conditions.

The pharmacokinetic objectives are central to the study, but the registry record does not report pharmacokinetic results. It consequently does not show the magnitude or precision of any food effect or cobicistat effect on plixorafenib. The listed urine excretion outcomes also lack numerical results in the record. No conclusion about those questions can be drawn from the safety counts.

These findings concern healthy participants receiving single doses, as described in the registry. They do not describe repeated dosing, other populations, or outcomes outside the recorded follow-up. The number enrolled was 28, but the registry lists 12 participants at risk for each treatment condition; the record does not explain the relationship between total enrollment and condition-specific safety denominators. Interpretation should stay with the populations and outcomes actually described rather than extending these counts to settings not reported.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a study’s scientific objectives and its registered primary endpoint. The stated objectives focus on plixorafenib pharmacokinetics under food and cobicistat conditions, while the listed primary endpoint counts participants with treatment-emergent adverse events. Both kinds of outcomes can be relevant, but they answer different questions. A safety count cannot stand in for a pharmacokinetic estimate.

The crossover structure is also statistically important. In general, comparisons within participants can control for stable differences between people, but the validity and precision of those comparisons depend on sequence, period and carryover considerations and on the analysis used. The registry identifies the crossover design without reporting those details. This limits the extent to which the statistical interpretation can be reconstructed from the record.

The posted safety figures show why denominators, endpoint definitions and uncertainty matter. Counts are useful for describing what was recorded, but they do not by themselves establish a difference between treatment conditions. The serious-event counts are zero across the listed conditions, while other adverse-event counts vary. Without event details or comparative analyses, neither pattern supports a formal ranking of conditions.

Finally, the record’s missing inferential results are consequential for the pharmacokinetic questions. Treatment conditions and objectives alone do not reveal effect size or precision. Transparent reporting of outcome estimates, analysis methods, missing-data handling and multiplicity decisions would allow readers to assess how strongly the data address the intended questions. In their absence, the defensible interpretation is descriptive and limited to the reported safety counts and design details.

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 main limitation of interpretation is that the registry record does not report pharmacokinetic estimates, comparative results, confidence intervals or p-values, despite the study’s stated pharmacokinetic objectives. Numerical results for the listed urine excretion outcomes are also not reported. The available safety counts therefore cannot answer the central questions about food and cobicistat effects on plixorafenib pharmacokinetics.

The primary endpoint is described as participants with at least one TEAE, but the record does not provide event-level descriptions, severity, duration or relationship to treatment. It lists serious adverse event counts and other adverse event counts, yet does not explain the relationship of the other-event counts to the primary TEAE definition in additional detail. No serious adverse event terms are listed.

Important design and analysis details are absent. The treatment sequence, washout interval, period-specific procedures, analysis model, analysis populations, missing-data rules, and treatment of incomplete crossover observations are not reported in the registry record. These details are relevant when interpreting crossover comparisons. Multiplicity handling and the sample-size justification are also not reported.

Enrollment was 28, while each listed condition has 12 participants at risk. The registry does not explain the relationship between these figures, so the condition-specific counts should not be used to infer participant flow or overlap. The study is described in healthy participants and uses single-dose treatments; the record does not support extending the observations to other populations or dosing contexts. These limitations restrict conclusions to the design and descriptive results actually recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Participants. — NCT06385119.
• Registry record last updated 2026-03-27; status last verified 2026-03.
• Results first posted 2026-03-27.
• 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

NCT06385119 is a completed phase 1, randomized, open-label crossover study sponsored by Fore Biotherapeutics. It enrolled 28 healthy participants and examined single-dose plixorafenib pharmacokinetics and safety under fasting and meal conditions, with and without cobicistat. The recorded start date was 2024-04-24 and primary completion date was 2024-12-22.

The primary endpoint was the number of participants with at least one TEAE from the first dose to day 19 (Treatment Period 3). The registry reports 0 serious adverse events and 0 deaths for each listed treatment condition, along with condition-specific counts for other adverse events. Pharmacokinetic results, comparative analyses, uncertainty estimates, and detailed statistical methods are not reported in the registry record.