A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease (NCT03384966), a randomized phase 2 study. The primary outcome is Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation.

2. Clinical Question

The question is about platelet reactivity measured with VerifyNow®, not directly about heart attacks, strokes, or other clinical events. The registry description says the test reports P2Y12 reaction units and that 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation. The results therefore address a measured pharmacodynamic response to a single injection. They do not, by themselves, answer whether treatment changes longer-term cardiovascular outcomes.

3. Trial Design

The registry describes a phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled, multi-center study. It evaluated a single subcutaneous injection of selatogrel in adults with stable coronary artery disease. The listed treatment arms were selatogrel 8 mg, selatogrel 16 mg, and placebo. The study status is completed. The record gives a start date of 2018-01-24, a primary completion date of 2018-08-18, and an enrollment of 346.

Randomization means treatment assignment was determined by an allocation process rather than being selected solely by participants or study staff. Masking is intended to limit the influence of treatment knowledge on study conduct or assessment. The record labels masking as quadruple, but does not identify the four roles covered by that label. The parallel design means the listed arms were compared as groups; the record does not describe a crossover design.

The primary outcome was a count of participants meeting a platelet-response definition. The outcome timeframe extended from 15 minutes after injection up to 24 hours. Separate secondary outcomes listed maximum selatogrel plasma concentration, time to maximum concentration, and area under the plasma concentration-time curve from time zero to 24 hours. The registry record lists nine outcome measures and five analyses in total, but the definitions and results for all of them are not included in the information.

The analysis population for the primary endpoint is defined as randomized participants who received study treatment. The record does not report the method used to generate the randomization sequence, allocation concealment details, the roles masked, or the planned sample-size justification. Those design details should not be inferred from the labels alone.

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: Of the 16 participants not randomized: 9 were ineligible; 4 withdrew consent; 1 was lost to follow-up, 1 was not randomized based on the physician's decision and 1 didn't complete screening within the protocol-defined window.

Randomized at end of screening period

Reasons for not completing this period:

Treatment period

Follow-up period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set - all participants that were randomized and who had study treatment administered.

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: Full Analysis Set - all participants that were randomized and who had study treatment administered.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation, measured over From 15 minutes after administration of the subcutaneous injection up to 24 hours.

The primary endpoint counts participants who met a prespecified pharmacodynamic responder definition. Platelet reactivity was assessed using VerifyNow®, a point-of-care test that expresses results as P2Y12 reaction units (PRU). In the registry description, 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation. A participant counted as a responder if PRU was less than 100 starting from 30 minutes after study treatment and remained below that threshold for at least 3 hours. The endpoint timeframe is stated as from 15 minutes after injection up to 24 hours.

A responder count converts repeated measurements into a participant-level outcome: each participant either met the stated response definition or did not. This can make group comparisons easier to interpret than a series of measurements at multiple time points, while retaining a clinically interpretable threshold for the measured platelet response. It also discards some detail: participants just above and far above the threshold are both nonresponders under this definition, and the count does not describe the full pattern of PRU measurements.

This is a pharmacodynamic endpoint. It measures a biological response to study treatment, rather than a clinical event or a direct measure of how participants feel or function. Its interpretation should remain tied to the assay, threshold, and duration rule recorded for the endpoint. The registry record does not report a clinical-outcome endpoint in the results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports chi-squared analyses of the primary count outcome. In general, a chi-squared test compares observed group counts with the counts expected under a specified null hypothesis, such as equal response proportions between groups. It is commonly used for categorical outcomes when its assumptions are suitable. The record does not report additional details about the test implementation, such as whether a continuity correction or another variant was used.

What the odds ratio describes

An odds ratio compares the odds of an outcome in one group with the odds in another. Odds are distinct from probabilities: they compare the number with the outcome to the number without it. An odds ratio of 1 corresponds to equal odds under the comparison. Values greater than 1 indicate higher odds in the first group as ordered for the comparison; values less than 1 indicate lower odds. The reported odds ratios of 58.9 and 61.2 are the sponsor’s estimates for the respective dose-versus-placebo comparisons. They should not be read as the same numerical increase in probability or as a direct ratio of the responder counts.

How to read the confidence intervals

The reported intervals are 97.5% confidence intervals: 22.4 to 154.8 for the 8 mg comparison and 23.1 to 162.3 for the 16 mg comparison. In general, a confidence interval conveys uncertainty in an estimate under the statistical procedure used. A wide interval means the data are compatible with a broader range of effect sizes than a narrow interval. The intervals remain above the equal-odds value, but their breadth signals that the precise magnitude is not pinned down as closely as the direction of the comparison.

The registry reports p < 0.001 for each comparison. In general, a p-value measures how unusual data at least as incompatible with the null hypothesis as the observed data would be, if that null hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A small p-value also does not address possible bias, missing data, or whether the endpoint captures outcomes important to patients.

Why the endpoint definition matters

The outcome is a count based on a binary responder classification. The threshold and duration rule define what is counted; changing either rule could change the classification. A count outcome does not retain the full distribution of measured PRU values or show each participant’s time course. General statistical interpretation should therefore keep the analysis tied to the recorded definition: PRU less than 100 starting from 30 minutes and lasting for at least 3 hours, within the stated endpoint timeframe.

Counts are often compared using methods for categorical data, but the suitability of a particular test depends on the analysis details and data structure. The registry identifies chi-squared as the method. It does not report diagnostic checks, alternative tests, covariate adjustment, or a model accounting for factors beyond the treatment comparison. Such procedures should not be assumed.

Multiple comparisons and planning

Two dose-versus-placebo comparisons are reported for the primary endpoint. When several hypotheses are tested, the chance of at least one false-positive result can increase if no multiplicity procedure is used. The registry record does not report whether the primary comparisons were adjusted for multiplicity or how the stated confidence level relates to any planned testing strategy. The reported p-values and intervals should therefore be understood as posted, without assuming an unreported adjustment.

General sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These are planning illustrations, not observed power and not evidence of the trial’s original design justification. The registry record does not report the trial’s own sample-size justification. Planning estimates depend on their assumptions and do not change the uncertainty in the observed results.

Finally, the stated analysis population includes randomized participants who received study treatment. This definition does not, by itself, explain how missing endpoint measurements were handled or whether every randomized participant contributed to the comparison. Those analytic details are not reported in the registry record.

10. Analyses Reported by the Sponsor

The sponsor’s posted analyses compare each selatogrel dose with placebo using a chi-squared method and report odds ratios, confidence intervals, and p-values. For 8 mg, the reported odds ratio is 58.9 with a 97.5% confidence interval of 22.4 to 154.8 and p < 0.001. For 16 mg, the odds ratio is 61.2 with a 97.5% confidence interval of 23.1 to 162.3 and p < 0.001.

A simple unadjusted recalculation is not available for this count outcome in the posted comparison results: the registry record identifies the values as missing or not estimable for a two-arm comparison of this endpoint type. There is therefore no recalculated estimate to set alongside the sponsor’s estimates. The record does not flag a discrepancy between its analyses and any recalculation. The sponsor’s reported analyses are the available inferential results for these comparisons.

The distinction matters because an independently recalculated comparison, when available, would be a check based on posted summary statistics and would not replace the trial’s planned analysis. In this case, interpretation rests on the sponsor’s reported chi-squared comparisons and the displayed participant counts. The registry record does not provide enough detail to reconstruct additional adjusted or alternative analyses.

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome uses a defined responder count in three treatment arms, and the registry reports two dose-versus-placebo comparisons. Testing multiple hypotheses can raise the overall chance of a false-positive finding if the tests are treated as independent opportunities for significance without adjustment. Whether adjustment is necessary, and which procedure is appropriate, depends on the trial’s prespecified testing strategy. That strategy is not reported in the registry record. The reported p-values and confidence intervals should not be described as multiplicity-adjusted unless the record says so.

The record lists nine outcome measures and five analyses, but the information includes only three named secondary outcomes: maximum selatogrel plasma concentration, time to reach maximum concentration, and area under the plasma concentration-time curve from time zero to 24 hours. The complete set of analysis details, including the relationship between all outcomes and any testing hierarchy, is not reported in the registry record. The number of listed outcomes alone does not establish that every outcome was tested or that all tests had equal status.

The primary analysis population is defined as participants randomized and treated. That is a reported population definition, not a complete account of missing-data handling. The registry record does not report how missing PRU measurements, incomplete follow-up, or other unavailable endpoint data were treated, nor does it describe imputation or sensitivity analyses. It also does not report an interim-analysis plan, the randomization sequence-generation method, or a detailed statistical analysis plan.

These omissions limit assessment of how the analysis was planned and how robust the results are to alternative assumptions. They do not change the posted counts or the reported comparisons, but they mean readers should avoid assuming unreported procedures. In particular, the posted estimates should be interpreted as analyses of the defined treated population, with the handling of missing observations and multiplicity remaining unclear from the registry record.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (0.9%), syncope (0.9%), non-cardiac chest pain (0.9%), angina pectoris (0.9%), cardiac arrest (0.9%).

During the treatment period, the registry reports zero serious adverse events in each arm: selatogrel 8 mg, selatogrel 16 mg, and placebo. During follow-up, serious adverse events were reported for 5 participants in the 8 mg arm, 1 participant in the 16 mg arm, and 1 participant in the placebo arm. Deaths were reported for 1 participant in the 8 mg follow-up group and none in the other listed groups. These are counts in the registry record, not estimates of comparative risk or proof that treatment caused an event.

Other adverse events were reported for 36 participants during treatment with selatogrel 8 mg, 26 with selatogrel 16 mg, and 25 with placebo. During follow-up, the corresponding counts were 13, 10, and 13. These figures are separate from the serious adverse-event counts. The registry also lists serious-event terms with a reported frequency of 0.9% each: atrial fibrillation, syncope, non-cardiac chest pain, angina pectoris, cardiac arrest, and ventricular fibrillation.

Adverse-event counts depend on the recorded period, group, and event definition. The registry information does not provide event-level narratives, attribution to treatment, or a comparative statistical analysis of these safety counts. Small numbers of serious events make descriptive counts especially unsuitable as a stand-alone basis for precise comparisons. The figures describe what was reported; they do not determine causality or establish the relative safety of the treatments.

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

The posted results show that more participants met the defined platelet-response criterion in each selatogrel arm than in the placebo arm. The sponsor’s analyses report large odds ratios for both dose-versus-placebo comparisons, with confidence intervals above the equal-odds value and p-values of less than < 0.001. This is evidence about the primary pharmacodynamic endpoint as defined in the registry.

The endpoint is not a direct measure of clinical benefit. It classifies participants according to a PRU threshold and duration rule after a single injection. A result on this measure does not establish whether treatment prevents heart attacks or other cardiovascular events, changes long-term outcomes, or improves symptoms. The record does not report such results in the information. Nor do the posted comparisons answer whether the thigh and belly injection sites differ, despite that being mentioned as a study objective.

The estimates also have uncertainty. Confidence intervals communicate a range of effect sizes compatible with the data and analysis, and the intervals are broad. The point estimates should not be treated as exact effects. The p-values provide evidence against the tested null hypothesis under the reported method; they do not measure the probability that the treatment effect is real or the importance of the effect.

Safety counts are descriptive and include serious events and deaths across treatment and follow-up periods. They do not establish whether events were caused by study treatment, and the registry record does not present a comparative safety analysis in the information. The results therefore support a narrow statistical conclusion about the measured response, while leaving clinical outcomes, longer-term effects, injection-site differences, and several aspects of analysis conduct unreported.

14. Why This Trial Matters Statistically

This trial illustrates how a clinical study can produce a clear statistical contrast on a biological measurement without directly answering a clinical-outcome question. The primary endpoint converts a test result into a responder count using both a threshold and a duration requirement. Understanding those rules is essential: the statistical comparison applies to participants who met that particular definition, not to every possible interpretation of platelet activity.

It also demonstrates why an effect estimate and its uncertainty should be read together. The odds ratios are far from the equal-odds value, and the reported p-values are small, but the confidence intervals remain wide. Statistical evidence for a difference and precision about its size are related but distinct considerations. A p-value alone cannot summarize the full evidence.

The three-arm design offers two dose-versus-placebo comparisons, while the registry’s analysis details leave multiplicity procedures unreported. This is a useful reminder that multiple comparisons require attention to the planned testing strategy, not just the individual results. Likewise, a stated analysis population does not reveal how missing measurements were managed.

Finally, the separate safety counts highlight the difference between describing observed events and estimating comparative risk. Sparse event counts, lack of attribution information, and absent comparative analyses constrain what can be concluded. The trial’s statistical contribution is therefore specific: it reports responder counts and sponsor analyses for a short-term pharmacodynamic endpoint, alongside descriptive adverse-event figures. That scope should guide interpretation.

15. 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 endpoint is a threshold-based pharmacodynamic measure. It does not capture the full distribution or time course of PRU values, and its interpretation depends on the registered cutoff and duration rule. The primary results do not establish effects on clinical cardiovascular outcomes or longer-term response.

The study objective includes exploring whether injection location matters, but the posted primary comparisons are dose-versus-placebo comparisons. The registry record does not report a site-specific comparison or identify the injection site for each arm. The available results therefore do not answer that objective.

The sponsor-reported odds ratios have wide confidence intervals, leaving uncertainty about the precise magnitude of the comparisons. The registry record does not report whether multiplicity adjustments were used, how missing endpoint data were handled, or whether sensitivity analyses were conducted. It also does not report the original sample-size justification, interim analyses, or a detailed statistical analysis plan. These gaps limit evaluation of the prespecification and robustness of the analyses.

The safety information is presented as counts by period and arm. The record does not provide event-level details, causal attribution, or inferential comparisons for the safety outcomes. Counts alone cannot establish whether treatment caused an event or support precise comparative risk estimates.

The registry record identifies the study as randomized, quadruple-masked, parallel, and multi-center, but the detailed randomization and masking procedures are not reported in the information. The listed design labels do not supply those operational details. These limitations do not invalidate the posted results, but they constrain how broadly and precisely those results can be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease — NCT03384966.
• Registry record last updated 2026-07-29; status last verified 2022-11.
• Results first posted 2021-05-17.
• 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.

19. Record Summary

NCT03384966 is a completed phase 2 randomized, quadruple-masked, parallel, placebo-controlled study in adults with stable coronary artery disease. It evaluated a single subcutaneous dose of selatogrel at 8 mg or 16 mg against placebo. The registry reports an enrollment of 346 and identifies the primary outcome as the number of participants meeting a platelet-response definition based on VerifyNow® PRU measurements.

Responder counts were 102 of 114 for selatogrel 8 mg, 103 of 115 for selatogrel 16 mg, and 18 of 116 for placebo. The sponsor reported chi-squared odds-ratio comparisons of 58.9 and 61.2, respectively, each with p < 0.001 and a 97.5% confidence interval. The record also lists pharmacokinetic secondary outcomes and adverse-event counts by treatment and follow-up period.

The posted statistical results concern a pharmacodynamic endpoint. Details about multiplicity, missing-data handling, and several design and analysis procedures are not reported in the registry record.