Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS (NCT03852459), a randomized phase 2 study. The primary outcome is Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, double-blind, vehicle-controlled, parallel-group study of S-Ibuprofen Topical Gel 5% (AP0302) for delayed onset muscle soreness. The registry lists quadruple masking. Participants were assigned to an active arm or a placebo arm receiving vehicle topical gel. The record states enrollment of 251. The posted primary outcome summaries use 126 participants in the active arm and 125 in the placebo arm.

The study status is completed. The recorded study start date is 2018-01-12, and the primary completion date is 2019-04-04. Aponia Laboratories, Inc. is listed as the sponsor. The study description identifies analgesic efficacy and safety as its aims. Further details of the original protocol, including the planned allocation procedure, treatment duration, and the reasons for the selected enrollment, are not reported in the registry record.

The primary outcome was a continuous measure of movement-related pain over 0-24 hours after time zero. The Full Analysis Set was defined as randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment. This population definition is narrower than simply all randomized participants, because it requires both treatment exposure and an efficacy assessment. The record does not report how many participants were excluded from that set or why.

The registry also lists secondary outcomes addressing pain relief with movement, stiffness with movement, global assessment, pain differences at other time intervals, and treatment-emergent adverse events. The listed secondary time intervals extend through 48 hours for some measures. Their presence indicates that the study considered outcomes beyond the primary 24-hour measure, but the record does not report a full statistical analysis plan or enough information to reconstruct how all secondary outcomes were analyzed.

Randomization and masking are important design features because they can reduce systematic differences between groups and influence in outcome assessment. They do not remove uncertainty due to sampling variation, missing outcomes, or limitations in the analysis. The registry record does not report the details needed to assess implementation of masking, concealment of allocation, or procedures for handling departures from the intended treatment assignment.

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: A total of 434 subjects were screened in the study of which 251 subjects were randomized.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero, measured over 0-24 hours..

The primary endpoint was the sum of the time-weighted differences from baseline in pain intensity with movement over 0-24 hours after time zero, called SPIDMOVE. Pain intensity was assessed with the Pain Intensity Numerical Rating Scale, where 0 means no pain and 10 means the worst possible pain. The outcome description defines the endpoint as the area under the curve of changes from baseline. Differences between successive assessment times were combined using the trapezoid rule, a standard way to approximate the area under a curve from measurements collected at separate times.

Repeated pain ratings capture how symptoms change over time rather than relying on a single measurement. Combining them into a time-weighted score can reflect both the size and persistence of changes during the stated interval. According to the registry description, positive and higher scores indicate greater reduction in pain. The endpoint is expressed in score-hours, so its magnitude depends on both the pain-score scale and the time interval summarized.

This type of endpoint is useful when the research question concerns symptom change across a defined period. It also compresses repeated observations into one summary measure for a group comparison. That summary does not show every participant’s pain trajectory, and group means do not describe the full distribution of individual experiences. The record reports means and standard deviations, but it does not report the distributional shape or individual trajectories. Interpretation therefore relies on the defined score, the group summaries, and the uncertainty around the comparison rather than on the means alone.

7. Results Posted in the Registry

• Active Arm: mean -33.09 versus -29.09 on control; difference -4.00 (95% CI -11.56 to 3.56), standardized effect d = -0.13; z-test p = 0.300.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Active Arm: mean 4.06 versus 3.61 on control; difference 0.45 (95% CI -0.47 to 1.37), standardized effect d = 0.12; z-test p = 0.338.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Active Arm and the control. The interval gives the range of effects that remain compatible with the data.

The registry includes secondary measures addressing pain relief, pain-intensity differences over additional time intervals, stiffness with movement, global assessment, and treatment-emergent adverse events. The numerical comparison available for total relief with movement over 0-6 hours has a mean difference of 0.45, a 95% confidence interval from -0.470 to 1.37, and an unadjusted p-value of 0.338. Its interval includes zero, so this comparison does not provide a sharply determined direction of difference.

Considered alongside the primary outcome, the available numerical secondary comparison does not establish a clear contrast that changes the interpretation of the primary analysis. Secondary measures can capture different dimensions of symptoms or different time windows, so they may offer useful descriptive context. They should not be treated as interchangeable with the primary endpoint: total relief and time-weighted change in pain intensity are distinct summaries, and a result on one does not automatically confirm or refute a result on another.

The record lists several outcomes and intervals, but it does not report a multiplicity strategy. When many outcomes are examined, some may appear more notable by chance, particularly if each is assessed separately without adjustment. For that reason, unadjusted secondary results carry less confirmatory weight than a prespecified primary analysis. Their value is chiefly in describing the broader pattern and identifying questions that warrant planned testing, not in selecting an isolated favorable result.

The registry record does not report enough detail to judge the complete pattern of results across every listed secondary measure, including all model estimates and uncertainty. The secondary outcomes should therefore be interpreted within the limits of the numerical information posted and the absence of a reported analysis hierarchy.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• SPIDMOVE Over the Following Intervals: 0-6, 6-12, 0-12, 12-24, 24-36, 24-48, 0-36, 36-48 and 0-48 Hours Post-T0.
• Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval
• Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero
• Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero
• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

9. Statistical Interpretation

10. Statistical Methods Explained

SPIDMOVE is a continuous outcome: it can take a range of numerical values rather than representing a simple event count. The registry reports an arm mean and standard deviation for each group. A mean describes the group’s average score; a standard deviation describes how dispersed individual scores are around that average. Neither statistic alone captures the full distribution, and an average can conceal variation in individual responses.

What does the unadjusted mean difference represent?

The recalculated contrast compares the active-arm mean with the placebo-arm mean by subtracting the latter from the former. It is an unadjusted summary based on the posted group means and standard deviations, rather than the sponsor’s reported ANCOVA model. The estimated mean difference is -4.0. A negative estimate means the active-arm mean is lower on the numerical scale used for the endpoint; it does not establish that this direction is favorable. The endpoint’s stated interpretation is that positive and higher values indicate greater reduction in pain, so direction must be read using that definition.

An unadjusted comparison does not account for baseline or other covariates. In a randomized study, adjustment can be used to account for specified variables and may change the estimate or its precision. The record reports ANCOVA for the sponsor’s analysis, but the covariates and model details are not reported in the registry record. The recalculated estimate should therefore be kept distinct from the sponsor’s analysis rather than presented as a reconstruction of it.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimate. In general, a 95% confidence interval is produced by a procedure that, under its assumptions, would cover the target quantity in 95% of repeated samples. It is not a statement that there is a 95% probability that the particular fixed treatment contrast lies inside this specific interval. For the primary unadjusted comparison, the interval ranges from -11.56 to 3.557. Because it includes zero, the posted summary does not rule out no difference under the unadjusted analysis. It also spans values on either side of zero, so the direction is not pinned down by this interval.

The interval’s width reflects the amount of information and variability in the data, as well as the calculation’s assumptions. A narrow interval can indicate greater precision than a wide one, but precision is not the same as clinical importance. Without a reported threshold for a meaningful difference, the interval cannot by itself determine whether any values it contains would matter in practice.

What does the reported ANCOVA tell readers?

The registry identifies ANCOVA as the method used for the sponsor’s reported superiority analysis and gives p = 0.427. ANCOVA is a regression-based method that compares group outcomes while adjusting for covariates included in the model. In general, adjustment for prognostic baseline measures can improve precision when the model is appropriate. The p-value describes how unusual data at least as incompatible with a null hypothesis would be under the model’s assumptions; it does not give the probability that the null hypothesis is true, or the probability that a treatment works.

The record does not report an adjusted effect estimate, its confidence interval, the covariates included, model diagnostics, or details of missing-data handling. As a result, the reported p-value can be quoted, but readers cannot use the registry entry to independently assess the adjusted contrast or reproduce the analysis. The unadjusted recalculation and the ANCOVA result answer related, but not identical, statistical questions.

Why can over-dispersion matter?

For a continuous outcome, substantial variability relative to the average difference can make an estimate less precise. More generally, over-dispersion describes data variability that exceeds what a chosen statistical model expects. When a model underestimates variability, standard errors may be too small and confidence intervals or tests may be misleading. This is a general statistical consideration, not a reported finding about this trial: the registry record does not report evidence of over-dispersion, a model check, or an analysis correcting for it. The posted standard deviations describe spread in each arm, but do not alone establish whether a model’s assumptions were met.

How should multiple outcomes be treated?

The record lists multiple secondary measures and time intervals. When many hypotheses are tested, the chance of obtaining at least one apparently unusual result by chance can increase. Multiplicity procedures, such as a prespecified testing hierarchy or adjustment of significance levels, can address that concern, but the registry record does not report such a plan. Accordingly, an unadjusted secondary p-value should generally be treated as exploratory rather than as a stand-alone confirmatory result. The secondary summaries can still describe patterns and inform questions for future research, while the primary outcome and the analysis plan remain central to confirmatory interpretation.

Finally, randomization supports comparisons between assigned groups, while masking can limit some sources of bias in treatment administration and outcome assessment. These design features do not eliminate random error, missing-data concerns, or model dependence. The registry record documents the broad design and the defined primary population, but does not provide enough detail to evaluate every assumption underlying the reported analyses.

11. Confidence Intervals and Precision

The primary unadjusted mean difference is -4.0, with a 95% confidence interval from -11.56 to 3.557. This interval crosses zero. It therefore includes no difference and also includes values indicating a difference in either direction on the numerical scale. The estimate alone gives one central value, while the interval shows that the data are compatible with a broader range of possible unadjusted contrasts.

The interval’s endpoints should not be read as guaranteed limits on the true effect. They describe uncertainty under the statistical procedure and its assumptions. The registry reports arm standard deviations of 31.31 for the active arm and 29.76 for the placebo arm, indicating substantial spread around the group means relative to the estimated contrast. These values help explain why an estimate can remain uncertain even when arm means are available, but they do not reveal the full score distribution or whether the outcome has unusual features.

The sponsor’s ANCOVA analysis reports p = 0.427, but the registry does not report its adjusted estimate or confidence interval. Consequently, the precision interval belongs to the unadjusted recalculation, not to the sponsor’s adjusted analysis. The unadjusted p-value is 0.3; it should not be used as a substitute for the interval, because the interval communicates a range and direction of compatible values while a p-value summarizes evidence relative to a null hypothesis under a particular test.

Statistical precision and clinical importance are separate. The registry record does not report a threshold for a clinically meaningful SPIDMOVE difference. Without such a threshold, the interval cannot be classified as excluding or including all clinically important effects. It does show that the posted unadjusted comparison does not tightly isolate a single value or direction.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants, because this is a two-arm continuous-outcome comparison. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to a stated fraction of the observed effect: 100%, 75%, or 50%. These are planning illustrations based on the observed effect, not the trial’s original design assumptions. The original design assumptions are not reported in the registry record.

For the primary outcome, planning for 100% of the observed effect gives 916 participants per arm for 80% power and 1,226 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,628 participants per arm for 80% power and 2,180 participants per arm for 90% power. Planning for 50% of the observed effect gives 3,663 participants per arm for 80% power and 4,904 participants per arm for 90% power.

In plain terms, the 80% power column describes a planning target at which the assumed design would have an 80% chance of detecting the specified effect at the stated significance level, if the model assumptions hold. The 90% column uses a higher chance of detection and therefore requires a larger planned group size under the same assumptions. Smaller effects are harder to distinguish from random variation, so detecting a smaller fraction of the observed effect requires more participants per arm.

The curve is read as a planning relationship between the effect size assumed and the number of participants required. It does not show what the completed study actually had power to detect. These calculations are not observed power: they are prospective illustrations using the observed effect as an input, and they do not establish the original rationale for enrollment or the likelihood that the trial would produce a particular result.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -4.000; pooled standard deviation σ = 30.550.
2. n = 2 × (1.96 + 0.842)² × 30.550² / -4.000² = 915.7, rounded up to 916 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -4                      # observed difference in means
sigma <- 30.5499147213528                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3852459)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 916 (80% power), 1,226 (90% power)
 75% of observed effect: n per arm = 1,628 (80% power), 2,180 (90% power)
 50% of observed effect: n per arm = 3,663 (80% power), 4,904 (90% power)
power.t.test: 916.6 
Simulated power at n = 916 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using ANCOVA for the primary superiority comparison, with p = 0.427. ANCOVA compares outcomes while adjusting for covariates included in the model. The registry record does not report the covariates, adjusted estimate, confidence interval, or further model details, so the adjusted result cannot be independently reconstructed from the entry.

The recalculated comparison is an unadjusted difference between the posted group means. It is -4.0, with a 95% confidence interval from -11.56 to 3.557 and an unadjusted p-value of 0.3. This calculation does not reproduce the ANCOVA analysis and does not account for any covariates the sponsor may have used. The different p-values are therefore not a direct contradiction: they arise from analyses that may differ in adjustment and calculation.

The discrepancy flag is false, so the record does not identify a discrepancy between the sponsor’s analysis and the recalculation. Still, the two results should be reported with their methods attached. The sponsor’s reported p-value is the registry’s stated result for its ANCOVA superiority analysis; the recalculation offers a transparent, unadjusted comparison of the posted summary statistics. Neither p-value alone indicates the size or practical importance of a treatment contrast, and the missing adjusted estimate limits interpretation of the sponsor model’s magnitude and precision.

15. Multiplicity, Missing Data and Analysis Populations

The record lists one primary endpoint and multiple secondary outcomes, including pain measures over several time intervals. Testing multiple outcomes or intervals creates a multiplicity concern: if each is tested separately, the chance of at least one apparently positive result due to random variation can increase. Statistical plans may address this with a hierarchy, adjusted significance thresholds, or other prespecified procedures. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

The registry identifies an ANCOVA superiority analysis for the primary outcome and gives its p-value, but it does not report the covariates or a fuller model specification. It also does not state whether there were interim analyses, how interim looks might have affected inference, or what statistical plan governed the secondary outcomes. These details are not reported in the registry record, so no assumptions should be made about them.

The Full Analysis Set includes randomized participants who received at least 1 dose and had at least 1 post-baseline efficacy assessment. This definition describes who qualified for the primary efficacy analysis, but it does not establish that every randomized participant was included. The record does not report the number excluded from that population, reasons for exclusion, or how missing measurements were handled. It also does not report whether a different analysis population was used for safety or other outcomes.

Missing-data methods matter because participants without post-baseline measurements may differ from those with observed outcomes. Complete-case analysis, imputation, and model-based approaches rely on different assumptions; those are general methods, not methods confirmed for this trial. The registry record does not report the assumptions used or sensitivity analyses assessing how missing observations could affect the result.

These omissions limit independent assessment of the analysis, but they do not show that the methods were inappropriate. They mean that readers cannot verify how multiplicity, missingness, analysis populations, or interim monitoring were addressed from the registry entry alone. The posted ANCOVA p-value and unadjusted recalculation should therefore be interpreted as results with distinct methods and with important analysis details unreported.

16. 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 posted serious adverse event figures report 0 affected participants among 126 at risk in the active arm and 0 among 125 at risk in the placebo arm. Deaths are reported as 0 in each arm. The registry record also gives no serious adverse event terms in its listed serious-event summary.

These counts describe what was recorded in the registry for the stated groups. Zero reported serious adverse events does not establish that the risk is absent, nor does it rule out uncommon events. Safety estimates depend on the size and follow-up of the study, how events were collected, and how they were classified. The record does not report enough detail to assess event surveillance or the duration of safety observation.

The record separately reports other adverse events affecting 123 of 126 participants in the active arm and 117 of 125 in the placebo arm. These are not serious adverse event counts and should not be conflated with the serious-event figures. The posted counts do not establish that an event was caused by study treatment. Interpretation of safety requires event types, timing, severity, and attribution details, which are not reported in the registry record in the information available for this analysis.

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

The registry results describe a randomized, masked comparison of S-Ibuprofen topical gel with vehicle gel for delayed onset muscle soreness. For the primary movement-related pain measure over 0-24 hours, the posted means were -33.09 and -29.09, and the unadjusted recalculated difference was -4.0. Its 95% confidence interval ranged from -11.56 to 3.557, and the unadjusted p-value was 0.3. The sponsor’s reported ANCOVA analysis gave p = 0.427.

These results do not provide clear statistical evidence of a difference in the primary outcome under the reported analyses. They also do not prove that the groups were equivalent or that the true difference was zero. The confidence interval includes zero and a range of values in both directions; the available information does not establish which values would be important to participants. The registry does not report a threshold for clinical importance.

A p-value is not the probability that a treatment works, nor is it the probability that the observed finding occurred by chance in a simple everyday sense. It is a measure of how compatible data are with a specified null model, conditional on the analysis assumptions. Similarly, a group mean difference is not a prediction for an individual participant. Individual outcomes can vary substantially around group averages.

The secondary outcome information may describe other aspects of pain or response, but multiple outcomes need cautious interpretation, especially without a reported multiplicity plan. Safety counts are also descriptive: zero reported serious adverse events in each arm does not prove an absence of risk. The record does not provide enough detail to make broader conclusions about all possible adverse effects, longer-term outcomes, or participant subgroups.

The appropriate statistical reading is therefore bounded: the posted data characterize this trial’s group summaries and analyses, with uncertainty around the primary comparison and incomplete reporting of some methods. They do not by themselves settle whether the observed contrast is clinically meaningful, whether it generalizes to other populations, or what an individual should do. Those are not conclusions established by these registry results.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through the outcome definition, estimate, uncertainty, and analysis method together. The primary measure combines repeated pain assessments into a time-weighted summary. That approach uses more of the symptom trajectory than a single rating, but it also requires attention to the direction and scale of the composite score. Here, the outcome description says higher positive values indicate greater reduction in pain, so a lower group mean cannot automatically be described as favorable.

The numerical estimate and its confidence interval tell different but complementary parts of the story. The mean difference is a single summary of the observed contrast; the interval shows that the estimate is uncertain and compatible with values on either side of zero. A p-value alone would not convey that range. The sponsor’s ANCOVA p-value adds a model-based analysis, but the absent adjusted estimate and model details make it harder to assess its magnitude and precision independently.

The planning illustration also shows the distinction between observing a result and designing a future study around a target effect. The required number of participants rises as the target effect becomes smaller, and a higher power target requires more participants under the stated assumptions. Those planning values are not a retrospective measure of the completed trial’s power and do not explain the original enrollment choice.

Finally, the registry lists multiple secondary measures, while the multiplicity plan and missing-data methods are not reported. That makes careful separation of confirmatory and exploratory evidence important. These issues are common in clinical research: design labels alone do not establish the credibility of every inference, and a non-significant result does not establish equivalence. The record is most informative when its estimates are read with their stated endpoint definitions and reporting limits.

19. 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 registry entry does not report the adjusted ANCOVA estimate or confidence interval, or the covariates included in that analysis. The sponsor’s p-value can be identified, but the magnitude and precision of the adjusted comparison cannot be assessed from that result alone. The unadjusted recalculation is a separate analysis and does not fill in those missing model details.

The record does not report the original sample-size assumptions or a justification for the planned enrollment. The planning calculations based on the observed effect are illustrations and cannot be taken as the study’s prospective design rationale. The record also does not report a clinically meaningful threshold for the SPIDMOVE score, limiting interpretation of whether the interval includes differences that would matter in practice.

The Full Analysis Set definition is stated, but the number of participants excluded from it, reasons for exclusion, and missing-data procedures are not reported in the registry record. This limits assessment of how incomplete follow-up or absent post-baseline measurements could influence the primary comparison. Further details about adherence and departures from assigned treatment are also not reported in the information available for this analysis.

Multiple secondary outcomes are listed, but no multiplicity procedure or testing hierarchy is reported. The completeness of numerical results across all the listed secondary outcomes cannot be assessed from the information available for this analysis. The registry also does not report interim analysis details, model diagnostics, or a full statistical analysis plan.

For safety, the registry provides counts of serious and other adverse events, but event descriptions and detailed timing or attribution information are not reported in the information available for this analysis. These limitations concern what can be evaluated from the registry record; they do not establish that the underlying study lacked the methods or data in question.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS — NCT03852459.
• Registry record last updated 2022-01-25; status last verified 2021-05.
• Results first posted 2022-01-25.
• 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.

23. Record Summary

NCT03852459 is a completed phase 2 randomized, double-blind, quadruple-masked, parallel-group, vehicle-controlled study of S-Ibuprofen Topical Gel 5% (AP0302) for delayed onset muscle soreness. Aponia Laboratories, Inc. is listed as sponsor. The recorded study start date is 2018-01-12, and the primary completion date is 2019-04-04.

The primary endpoint was SPIDMOVE over 0-24 hours after time zero. The active-arm mean was -33.09 and the placebo-arm mean was -29.09. The unadjusted recalculated mean difference was -4.0, with a 95% confidence interval from -11.56 to 3.557 and an unadjusted p-value of 0.3. The registry reports an ANCOVA superiority analysis with p = 0.427.

The results do not establish a clear primary-outcome difference or equivalence. The interval reflects uncertainty, while several analysis details, including the adjusted estimate, missing-data methods, and multiplicity plan, are not reported in the registry record. Serious adverse events and deaths were reported as 0 in each arm; other adverse event counts were 123 of 126 in the active arm and 117 of 125 in the placebo arm.