Safety and Efficacy of Bepotastine Besilate Nasal Spray in the Treatment of Seasonal Allergic Rhinitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Bepotastine Besilate Nasal Spray in the Treatment of Seasonal Allergic Rhinitis (NCT01277341), a randomized phase 2 study. The primary outcome is Mean Change From Baseline (Pre-Dose) in Subject-rated Reflective TNSS.

2. Clinical Question

The posted arm means show a decrease from baseline in every group. The recalculated unadjusted mean differences versus placebo are negative for all three concentrations. These estimates describe the posted results; they do not establish the trial’s prespecified statistical conclusions, which are not reported in the registry record.

3. Trial Design

This was a completed phase 2 randomized, double-masked, parallel-group trial of bepotastine besilate nasal spray for seasonal allergic rhinitis. The registry lists 601 participants enrolled and four groups: 2%, 3%, and 4% spray taken twice a day, and placebo nasal spray. The registry record does not report the allocation ratio or additional details about how randomization and masking were implemented.

The trial began in 2010-12, and primary completion was recorded in 2011-02. The primary outcome timeframe compares baseline with 14 days. The posted analysis population included all randomized participants, with no imputation of missing data at 14 days. Outcome counts vary across the four groups; the registry record does not report further reasons for this or details about missing outcome values.

The primary measure was a continuous score, summarized by a mean and standard deviation in each group. One outcome measure is posted, and no analyses are listed in the registry record. The three comparisons with placebo discussed in the results are recalculated, unadjusted comparisons from the posted summary statistics; they should not be mistaken for the trial’s prespecified analysis. The registry record does not report the original sample-size justification or a detailed statistical analysis plan.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All randomized participants were included in the analysis population, with no imputation of missing data at 14 days.

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 Mean Change From Baseline (Pre-Dose) in Subject-rated Reflective TNSS, measured over Baseline, 14 days.

The primary endpoint is mean change from baseline in subject-rated reflective total nasal symptom score (TNSS) over 14 days. TNSS combines ratings for nasal itching, runny nose, nasal congestion, and sneezing. Each symptom is rated from 0 to 3, with 0 meaning absent and 3 meaning severe; half-unit assessments are not used. The four ratings are summed to produce a score from 0 to 12, and higher scores correspond to more nasal allergy symptoms. Morning and evening scores were averaged.

A change score describes how the measured symptom score differs from the participant’s baseline score. A negative mean change therefore represents a lower score at follow-up than at baseline. Comparing mean change between a spray group and placebo gives an estimate of the difference in average change between those groups.

A subject-rated symptom measure captures participants’ own reports of symptoms, which are central to the outcome being assessed. It also compresses several symptoms into one overall score. That summary is useful for comparing average changes, but it does not show the separate pattern for each symptom. The registry record does not report secondary outcome measures.

7. Results Posted in the Registry

• 2% Twice a Day: mean -1.84 versus -0.99 on control; difference -0.85 (95% CI -1.27 to -0.43), standardized effect d = -0.49; z-test p = <0.001.
• 3% Twice a Day: mean -1.71 versus -0.99 on control; difference -0.72 (95% CI -1.16 to -0.28), standardized effect d = -0.39; z-test p = 0.001.
• 4% Twice a Day: mean -1.47 versus -0.99 on control; difference -0.48 (95% CI -0.92 to -0.04), standardized effect d = -0.27; z-test p = 0.031.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is continuous: it is a score that can take values across a numerical scale. The registry summarizes each group with a mean and standard deviation. The mean describes the group’s average change from baseline; the standard deviation describes how spread out participant scores are around that average. A mean is a useful summary, but it does not imply that every participant had a change close to that value.

What does the mean difference represent?

A mean difference compares the average change in one spray group with the average change in the placebo group. The recalculated contrasts use the posted group means. Because lower TNSS corresponds to fewer reported nasal symptoms, a negative contrast indicates a more negative average change in the spray group than in placebo. For example, the recalculated contrast for 2% spray is -0.85. This is a difference between group averages, not a statement about an individual participant’s outcome.

The three contrasts are unadjusted recalculations from posted summary statistics. The registry record does not report the formal method used for the trial’s own analysis, and it lists no analyses. Thus, these recalculated results should be distinguished from any sponsor analysis or prespecified result.

What does a standard deviation tell the reader?

Standard deviations describe variability among participant scores within a group. A larger standard deviation means scores are more dispersed around the group mean; it does not indicate whether the mean change is more or less favorable. The posted standard deviations range from 1.69 to 1.97 across the four groups. Variation matters because a mean difference must be interpreted in the context of how much scores vary and how many participants contribute to the estimate.

In general, when an outcome is continuous, comparing group means can be informative if the mean is an appropriate summary and the analysis accounts for the design and uncertainty. The registry record does not report diagnostic checks or the assumptions used in the original outcome analysis. No conclusion about those checks can be drawn from the posted summaries alone.

How should the p-values be read?

A p-value describes how compatible data are with a specified statistical null model, under the assumptions of the method used. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The recalculated unadjusted p-values are < 0.001 for 2% spray, 0.001 for 3% spray, and 0.031 for 4% spray. Their interpretation is limited because the registry record does not state the trial’s analysis method or whether these comparisons were planned in advance.

There are three spray-versus-placebo comparisons. When several hypotheses are tested, the chance of at least one apparently unusual result can change; statistical procedures can address this issue, depending on the analysis plan. The registry record does not report a multiplicity procedure. The posted p-values should consequently be read as unadjusted recalculations, not as evidence that multiplicity was handled in the trial’s formal analysis.

Why do confidence intervals matter?

A confidence interval gives a range of estimates compatible with the data and the method used to construct it. It communicates uncertainty around an estimated difference, rather than only whether a p-value is above or below a threshold. The recalculated intervals for all three contrasts lie below zero, while their widths show that the estimates are not exact. An interval’s interpretation depends on the statistical method and its assumptions; the registry record does not describe the trial’s own interval construction.

The intervals and p-values accompanying the contrasts are unadjusted recalculations from the posted summary statistics. They do not incorporate an unreported multiplicity adjustment. Differences in estimate size and interval width should be considered together: an estimate is not known exactly, and its precision is distinct from its magnitude.

What does the planning calculation add?

Planning calculations illustrate how sample size can depend on the effect a future study aims to detect and the chosen design assumptions. The registry record’s planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers targets based on 100%, 75%, and 50% of the observed effect. These are planning illustrations, not the trial’s original sample-size justification; that justification is not reported in the registry record. They are also not observed power.

For continuous outcomes, variability affects how much information each participant contributes to a group comparison. More variability generally makes a given difference harder to estimate precisely. The trial’s summary statistics allow unadjusted recalculations, but they do not reveal every detail of the original analysis, such as any covariate adjustment, handling of protocol deviations, or planned sensitivity analyses. Those details are not reported in the registry record.

10. Confidence Intervals and Precision

The recalculated intervals give a sense of uncertainty around each mean difference versus placebo. For 2% spray, the estimate is -0.85; for 3% spray, it is -0.72; and for 4% spray, it is -0.48. Each interval extends on both sides of its point estimate, so the estimate should not be treated as exact. All three intervals lie below zero, although the interval for 4% spray comes closer to zero than the other two.

Interval width is relevant to precision: a narrower interval represents a more precise estimate under the method used, while a wider interval leaves more uncertainty about the possible contrast. The intervals are unadjusted recalculations from the posted summary statistics. Their construction method and confidence level are not reported in the registry record, so they should not be attributed to the trial’s original analysis.

Precision is not the same as the size or importance of an effect. The 2% estimate is more negative than the 3% estimate, which is more negative than the 4% estimate, but the estimates alone do not establish a difference among the three concentrations. The posted results give comparisons with placebo, not direct comparisons between spray concentrations. The registry record does not report a formal dose-comparison analysis.

The group standard deviations indicate participant-to-participant variability, and the group outcome counts differ. Those features contribute to uncertainty in group comparisons. The posted summary statistics do not show individual outcomes or explain missing outcome values. No imputation was used at 14 days for the stated analysis population, so the reported summaries should be interpreted with that approach in mind.

11. 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 for 80% power and participants per arm for 90% power. They do not represent total events: the registry’s planning assumptions specify participants per arm for these non-time-to-event comparisons. The 80% column illustrates a design targeting an 80% chance of detecting the stated effect under the calculation assumptions if that effect is present. The 90% column uses a higher target chance of detection. Neither column describes power observed in this completed trial.

The calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For each comparison, the effect used for planning is set at 100%, 75%, or 50% of the observed effect. A smaller target effect is harder to distinguish from random variation under the same assumptions, so it requires more participants per arm. The planning curve is read in the same spirit: it relates the effect targeted to the number of participants required under the calculation assumptions.

These figures are planning illustrations based on observed effects, not the trial’s original sample-size justification. The original design assumptions and justification are not reported in the registry record. They should not be used to infer the probability that this trial found a true effect or to replace the posted estimates and their uncertainty.

12. 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 = -0.850; pooled standard deviation σ = 1.747.
2. n = 2 × (1.96 + 0.842)² × 1.747² / -0.850² = 66.3, rounded up to 67 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 <- -0.85                      # observed difference in means
sigma <- 1.74691134278295                     # 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(1277341)
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 = 67 (80% power), 89 (90% power)
 75% of observed effect: n per arm = 118 (80% power), 158 (90% power)
 50% of observed effect: n per arm = 266 (80% power), 356 (90% power)
power.t.test: 67.3 
Simulated power at n = 67 per arm: 0.797 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a statistical analysis plan, the number of comparisons prespecified for formal testing, or any procedure for adjusting for multiple comparisons. The three spray-versus-placebo contrasts are unadjusted recalculations from the posted group summaries. Their p-values should not be interpreted as multiplicity-adjusted results, and the registry record does not establish whether the trial’s own analysis addressed multiplicity.

Multiplicity matters when several hypotheses are assessed because the interpretation of individual p-values can change when considered as a family of tests. General statistical methods can control this issue, but the record does not identify a method used in this trial. It also does not report an outcome hierarchy or a distinction between confirmatory and exploratory comparisons.

The stated analysis population included all randomized participants, with no imputation of missing data at 14 days. This clarifies how missing values were treated for the posted primary analysis: missing values were not filled in by imputation. The registry record does not report how many outcome values were missing, why they were missing, or any sensitivity analysis assessing the effect of missingness.

The number of participants in the outcome summaries differs across groups. The registry record does not report the reasons for these counts, whether any participants discontinued treatment, or how protocol deviations were handled. It also does not report whether the original analysis used additional adjustments or other analysis populations. These gaps limit reconstruction of the trial’s formal inferential analysis from the registry record.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (0.7%).

The posted serious adverse event counts are 0 among 150 participants in the 2% group, 1 among 150 in the 3% group, 0 among 149 in the 4% group, and 0 among 152 in the placebo group. The serious event term listed is Death, at 0.7%. The group-level death counts are 0, 1, 0, and 0, respectively. These are descriptive counts; they do not establish that an event was caused by the assigned spray.

Other adverse events are listed for 25 participants in the 2% group, 22 in the 3% group, 22 in the 4% group, and 10 in the placebo group. The registry record does not report the event-collection timeframe, event definitions, severity criteria, or a comparative statistical analysis of adverse events. The safety groups’ at-risk counts also differ from the outcome counts. These figures should therefore be read as posted counts within the listed safety groups, not as adjusted comparisons of risk.

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

The posted results describe average change in subject-rated TNSS from baseline to 14 days in four randomized groups. Scores fell on average in each group, including placebo. The recalculated unadjusted contrasts indicate more negative mean change for each spray concentration than for placebo. Their estimates and intervals describe group-average differences and uncertainty, not guaranteed outcomes for individual participants.

The numbers do not by themselves establish the trial’s formal statistical conclusions. The registry record lists no analyses and does not report the original analysis plan, method, or any multiplicity adjustment. The p-values and intervals accompanying the three contrasts are unadjusted recalculations from posted summary statistics. The record does not report direct comparisons among the three concentrations, so the placebo comparisons cannot answer whether one concentration differs from another.

The results concern one subject-rated composite symptom score over 14 days. They do not describe each symptom separately, longer-term outcomes, or secondary endpoints. The registry record does not report the number or reasons for missing outcome values; the stated approach was to use no imputation at 14 days. The outcome counts differ among groups, and their causes are not reported.

Safety counts are also descriptive. A serious event and a death are listed in the 3% group, while no serious events or deaths are listed in the other groups. These entries alone do not determine causation or provide a complete comparative safety assessment. In general, interpretation of clinical trial results depends on design, measurement, uncertainty, missing data, and the analysis plan as well as point estimates. Several of those details are not reported in the registry record.

16. Why This Trial Matters Statistically

This trial offers a clear example of why a clinical result should be read through both its outcome definition and its statistical summaries. TNSS combines four participant-rated symptoms into a score, and its direction is important: higher scores represent more symptoms. Accordingly, negative changes describe lower scores relative to baseline, while negative between-group contrasts indicate a larger average decrease in the spray group than in placebo.

The three estimates differ in size, and their intervals convey uncertainty around those estimates. The registry record does not report a direct analysis comparing concentrations with one another, so the pattern of placebo comparisons should not be treated as proof of a concentration-response relationship. Nor do unadjusted p-values resolve the question of how multiple comparisons were handled.

The record also illustrates the distinction between a study’s original design and a later planning illustration. The posted planning calculations use stated assumptions and observed effects, whereas the original sample-size justification is not reported. Such illustrations can show how smaller target effects call for more participants, but they do not establish the design rationale for this completed trial or its observed power.

Finally, the posted results leave important context unspecified, including details of missing outcome values, the formal analysis plan, and safety-event definitions. Recognizing what the summaries can and cannot establish is essential to interpreting trial statistics without overstating their reach.

17. 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.

Several limitations are specific to the information recorded for this trial. The primary outcome is subject-rated and combines four symptoms into one score. The posted summary does not show symptom-specific results or individual participant outcomes, so it cannot describe whether the component symptoms changed in the same way for all participants.

The primary timeframe is 14 days. The registry record does not report longer-term outcomes. It also does not report the original sample-size justification, allocation ratio, detailed randomization and masking procedures, or formal statistical analysis plan. The listed sample-size calculation is a planning illustration based on observed effects, not a record of the trial’s own design assumptions.

The stated approach did not impute missing 14-day values. The registry record does not state the amount or pattern of missingness, reasons for missing values, or sensitivity analyses. Outcome counts differ across the four groups, but the record does not explain why. One outcome measure is posted and no analyses are listed, leaving the formal status of the recalculated contrasts and any planned adjustment for multiple comparisons unclear.

Safety information is limited to posted counts. Definitions, collection timeframe, severity criteria, and comparative analyses are not reported. The record also does not provide a direct comparison among the three concentrations. These limitations mean the registry summaries support a focused description of the recorded outcome and events, not a complete account of the trial’s conduct or analysis.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Efficacy of Bepotastine Besilate Nasal Spray in the Treatment of Seasonal Allergic Rhinitis — NCT01277341.
• Registry record last updated 2020-10-05; status last verified 2020-10.
• Results first posted 2020-09-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The registry record describes a completed phase 2 randomized, double-masked, parallel trial of bepotastine besilate nasal spray for seasonal allergic rhinitis. A total of 601 participants were enrolled across 2%, 3%, and 4% twice-daily spray groups and a placebo group. The primary outcome was mean change from baseline in subject-rated reflective TNSS at 14 days.

All four groups had negative mean changes. Recalculated unadjusted mean differences versus placebo were negative for each spray concentration. The registry lists one outcome measure and no analyses. It reports no imputation of missing 14-day outcome values, and its serious adverse event counts include one event, listed as Death, in the 3% group. Important details about the original analysis plan, missing values, and safety-event methods are not reported in the registry record.