Efficacy and Safety of SPARC1310 in Seasonal Allergic Rhinitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of SPARC1310 in Seasonal Allergic Rhinitis (NCT01940146), a randomized phase 2 study. The primary outcome is Change in Total Nasal Symptom Score From Baseline to Day 14..

2. Clinical Question

The clinical question is framed around a short-term change in a symptom score. It is not a question about long-term outcomes, individual symptoms considered separately, or comparisons between each active group and an active control. The registry record reports one primary outcome measure and no posted secondary outcomes.

The reported group values are least-squares mean changes. The placebo group’s value is -2.7 units, while the S0597 Low Dose, Mid Dose, and High Dose values are -4.05, -4.72, and -4.05 units, respectively. Because higher TNSS scores indicate greater severity, a negative change represents a decrease in the score. The posted contrasts quantify how the reported changes in the three S0597-labeled groups compare with the placebo change.

The registry record does not report details needed to fully reconstruct the clinical comparison, including the precise intervention doses, the active control identity, eligibility criteria, or the definition of the analysis population. The arm-label discrepancy should therefore remain visible when interpreting which interventions the numerical results describe.

3. Trial Design

This was a randomized, double-masked, parallel phase 2 trial marked completed in the registry record. Enrollment is reported as 222. The record lists a start of 2014-10 and primary completion of 2014-12. Those dates place the stated primary endpoint in a short-term study period, but the record does not give a more detailed schedule of visits or follow-up.

Four arms appear in the outcome data: placebo and three S0597-labeled dose groups. The reported arm sizes are 56 for placebo, 55 for S0597 Low Dose, 56 for S0597 Mid Dose, and 55 for S0597 High Dose. The record separately names the interventions SPARC Placebo and SPARC1310 I, II, and III. It does not state explicitly how those intervention names map to the S0597 outcome labels. The registry’s brief summary says the study assesses SPARC1310 against placebo and active control, but an active-control arm is not identified among the posted outcome groups.

Randomization means allocation was intended to be governed by chance rather than by participant or investigator choice. Double masking generally means that treatment assignment is concealed from participants and specified study personnel; the registry record does not say who was masked or describe how masking was maintained. A parallel design means groups receive their assigned interventions during the same study period rather than switching through a sequence of treatments. These are general explanations of the design terms, not additional protocol details.

The registry record does not report the randomization method, allocation ratio, dose levels, treatment duration, sample-size justification, or original statistical analysis plan. It also does not provide a detailed account of recruitment, discontinuations, adherence, or the handling of participants with missing Day 14 measurements. The design description can therefore establish the broad comparison structure, but not all the operational features needed to judge conduct or reproduce the analysis.

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

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 Change in Total Nasal Symptom Score From Baseline to Day 14., measured over Baseline to Day 14.

The primary endpoint is change in Total Nasal Symptom Score (TNSS) from baseline to Day 14. The score adds ratings for nasal congestion, rhinorrhea, nasal itching, and sneezing. Each symptom is rated on a four-point intensity scale: 0 for none, 1 for mild, 2 for moderate, and 3 for severe. The resulting total ranges from 0 to 12, with higher scores indicating greater symptom severity.

A change score expresses how much the measured outcome moved from its baseline value over the stated interval. In this trial, the reported arm values are negative, indicating decreases in TNSS between baseline and Day 14. The endpoint is used to represent the combined intensity of several nasal symptoms rather than an isolated symptom or a broader measure of health.

The record reports least-squares mean change and standard error for each group. A least-squares mean is generally a model-based estimate of a group mean; the registry record does not describe the model, covariates, or adjustments used to obtain these values. The standard error describes the statistical precision of an estimated mean, not the spread of individual participants’ scores.

The endpoint provides a defined, score-based way to compare short-term symptom changes. Its interpretation depends on the scale and the reported time point. The record does not report a threshold for a clinically meaningful change, nor does it provide separate results for each symptom in the score. The posted endpoint therefore addresses average change in the combined score, not whether a particular individual experienced a meaningful improvement.

7. Results Posted in the Registry

• S0597 Low Dose: mean -4.05 versus -2.70 on control; difference -1.35 (95% CI -2.40 to -0.30), standardized effect d = -0.48; z-test p = 0.012.
• S0597 Mid Dose: mean -4.72 versus -2.70 on control; difference -2.02 (95% CI -3.07 to -0.97), standardized effect d = -0.71; z-test p = <0.001.
• S0597 High Dose: mean -4.05 versus -2.70 on control; difference -1.35 (95% CI -2.41 to -0.29), standardized effect d = -0.47; z-test p = 0.013.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: it is a numerical score that can take values across a scale. The registry reports a least-squares mean change for each arm and a standard error. In general, a mean describes the average outcome in a group, while a standard error describes uncertainty in the estimated mean. It is not the same as the standard deviation, which describes variation among individual observations. The registry record does not identify the model used for the least-squares means or whether particular baseline variables were included.

What does the mean difference represent?

A mean difference compares the average change in one group with the average change in another. Here, the posted contrasts use placebo as the comparator. The Low Dose contrast is -1.35, the Mid Dose contrast is -2.02, and the High Dose contrast is -1.35. The direction follows the signed scale: because a decrease in TNSS is negative, a more negative change in a treatment-labeled group produces a negative difference relative to the placebo change. The contrast is expressed in TNSS units, not as a percentage or a ratio.

The posted means and contrasts are unadjusted group comparisons in the sense that the listed estimates do not show adjustment for multiple comparisons. The record does not state whether the original sponsor analysis used a more complex adjustment or another model. The posted comparison values should therefore be interpreted according to what is recorded, not as a complete description of the trial’s original analysis procedure.

How should the confidence intervals be read?

A confidence interval gives a range of values compatible with the observed data under a specified statistical procedure. Its width conveys precision: narrower intervals indicate more precise estimates, while wider intervals indicate more uncertainty. The Low Dose interval is -2.402 to -0.298; the Mid Dose interval is -3.072 to -0.968; and the High Dose interval is -2.412 to -0.288. Each interval is entirely negative, consistent with a negative estimated contrast. A confidence interval is not a guarantee that the true value falls inside its endpoints, nor does it describe the range of individual participant outcomes.

The record reports p-values as unadjusted: 0.012 for Low Dose, <0.001 for Mid Dose, and 0.013 for High Dose. A p-value measures how compatible the data are with a specified null hypothesis under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not describe the test statistic, degrees of freedom, or whether these p-values reproduce the sponsor’s planned analysis.

What does the standardized effect add?

The posted contrasts also include standardized effect estimates, d, of -0.477 for Low Dose, -0.711 for Mid Dose, and -0.473 for High Dose. Standardization expresses a mean difference relative to a measure of variability, placing the result on a scale that is not tied to TNSS units. It can help describe magnitude across measures, but it does not replace the original-unit contrast or establish clinical importance. The pooled standard deviations are marked approximate because they were inferred from the reported standard errors and group sizes; the record does not supply participant-level variability directly.

That approximation matters because summary statistics do not preserve all the information available in individual observations. A recalculation from arm means, standard errors, and sizes can be useful as a transparent, unadjusted comparison, but it may not reproduce a model-based analysis that uses participant-level data, covariate adjustment, or a different missing-data procedure. The registry record does not describe whether such features were used in the trial’s own analysis.

Why does multiplicity matter?

When several hypotheses are tested, the chance of obtaining at least one apparently small p-value can increase if each test is judged separately. Statistical procedures can control this issue by adjusting significance thresholds or p-values, or by defining a hierarchy of tests. The record contains three posted contrasts against placebo, but does not report a multiplicity procedure. The unadjusted results should consequently not be treated as evidence that any family-wise error control was applied. The trial’s prespecified approach is not reported in the registry record.

What can the design tell us about inference?

Random allocation is generally intended to make groups comparable on average at the start of a study, while masking can reduce some influences of knowledge about assignment. Those design features support interpretation of between-group comparisons, but they do not remove uncertainty or guarantee that all biases are absent. The record does not specify how the random sequence was generated, who was masked, or whether masking remained intact. It also does not report an analysis population or missing-data method.

For the same reason, the reported arm means and contrasts should be read with their documented limits. They describe the recorded outcome values for the identified groups and time point. They do not establish the performance of unreported analyses, and they do not resolve the difference between the SPARC1310 intervention names and the S0597 outcome labels.

10. Confidence Intervals and Precision

The posted confidence intervals quantify uncertainty around each mean-difference estimate. For S0597 Low Dose, the estimate is -1.35, with an interval from -2.402 to -0.298. For S0597 Mid Dose, the estimate is -2.02, with an interval from -3.072 to -0.968. For S0597 High Dose, the estimate is -1.35, with an interval from -2.412 to -0.288. Each interval lies on the negative side of zero, so the reported interval estimates are consistent with a greater average TNSS decrease in the named group than in placebo.

The intervals also show that the precise contrast is uncertain. For example, the Mid Dose interval includes values ranging from a more pronounced negative contrast to a contrast closer to zero. The Low Dose and High Dose intervals have similar spans, and both include estimates close to zero as well as more negative differences. The interval endpoints should be considered alongside the point estimates rather than treating the point estimate as exact.

Precision is distinct from clinical importance. The registry record does not provide a threshold for a meaningful change in TNSS, so the intervals cannot be used to decide whether the estimated differences cross such a threshold. Nor do they describe individual responses: an interval around a group contrast is not a range containing most participants’ outcomes.

The arm-level standard errors are reported as 0.381 for placebo, 0.378 for Low Dose, 0.378 for Mid Dose, and 0.385 for High Dose. These quantify precision of the reported arm means under the analysis that produced them. The registry record does not provide the model details or participant-level data needed to independently verify that precision. The posted interval estimates are therefore best read as the uncertainty attached to the reported comparisons, with the analysis assumptions and population definition not reported in the registry record.

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 sample-size figures are planning illustrations expressed as participants per arm, not total event counts. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses the stated fraction of the observed effect as the effect to detect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The column for 80% power gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is present. The 90% power column gives the corresponding per-arm planning number for a design with a 90% chance under those assumptions. Power is a property of a planned design for a chosen effect size and analysis; it is not a measure of what the completed trial demonstrated.

The rows describe planning for 100%, 75%, and 50% of the observed effect. Smaller effects require more participants per arm to reach the same target power under the same assumptions. For example, planning for 50% of the observed effect requires more participants per arm than planning for the full observed effect in each displayed comparison. The displayed values differ by contrast because the observed effect estimates differ.

These figures are not observed power. They are illustrations based on the observed estimates, not evidence that the trial was designed with those assumptions or that it had a particular chance of success after completion. They should be used as conditional planning references rather than as a retrospective score for the trial.

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 = -1.350; pooled standard deviation σ = 2.828.
2. n = 2 × (1.96 + 0.842)² × 2.828² / -1.350² = 68.9, rounded up to 69 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 <- -1.35                      # observed difference in means
sigma <- 2.82755342100266                     # 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(1940146)
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 = 69 (80% power), 93 (90% power)
 75% of observed effect: n per arm = 123 (80% power), 164 (90% power)
 50% of observed effect: n per arm = 276 (80% power), 369 (90% power)
power.t.test: 69.8 
Simulated power at n = 69 per arm: 0.791 (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 record posts three comparisons with placebo, each with an unadjusted p-value. It does not report whether the trial prespecified a multiplicity strategy, such as adjustment across the three comparisons or a testing hierarchy. Without that information, the posted p-values cannot be interpreted as evidence that the family of comparisons was protected against an increased chance of false-positive findings. Their unadjusted status is important when considering the apparent evidence across several groups.

The record reports one primary outcome measure and no posted secondary outcomes. It does not provide the full statistical analysis plan, identify all planned outcomes or analyses, or say whether additional analyses were conducted but not posted. The number of analyses listed is zero, but the posted comparison results still give estimates and p-values; the record does not explain this difference in reporting. The statistical plan and any interim analyses are not reported in the registry record.

Missing-data handling is also not reported in the registry record. There is no description of how participants without a Day 14 score were treated, whether imputation was used, or how adherence and discontinuation affected analysis. The arm sizes listed with the outcome are available, but the record does not identify whether they represent all randomized participants, participants with measured outcomes, or another analysis set. It does not name an intention-to-treat, per-protocol, or safety population.

These omissions limit assessment of whether the posted estimates include all randomized participants and whether missing outcomes could have affected the comparisons. Randomization supports an unbiased comparison when the analysis and outcome data preserve the intended group comparison, but missingness and analysis choices can change that interpretation. The record does not provide enough information to determine those details.

The registry record does not report the original sample-size justification, any planned interim monitoring, or the criteria used to select analyses. Those details should not be inferred from the planning illustrations, which are based on observed effects and stated assumptions for illustrative future planning rather than the trial’s own design.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 report zero affected participants in each listed group: placebo, SPARC1310 I, SPARC1310 II, and SPARC1310 III. The corresponding groups at risk are reported as 56, 55, 56, and 55. These are counts in the registry record, not a comparative statistical analysis. The record lists no serious adverse-event terms.

Other adverse events are recorded for 2 participants in the placebo group, 3 in SPARC1310 I, 4 in SPARC1310 II, and 4 in SPARC1310 III. The record does not give event types, severity, timing, attribution, or whether the entries refer to participants with at least one event or to event occurrences. The counts therefore should not be interpreted as a complete characterization of the safety profile.

Deaths are not reported in the registry record. The absence of a reported serious event in these groups does not establish that no other safety concerns occurred, and the posted counts do not by themselves support a statistical comparison of risk. The short-term endpoint period and limited detail in the registry record should be kept in mind when reading these safety results.

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

The posted outcome data describe average TNSS change from baseline to Day 14 in placebo and three S0597-labeled groups. All reported group means are negative, and each posted contrast against placebo is negative. The contrast intervals do not include zero, and the listed p-values are unadjusted. These observations describe the recorded score comparisons; they do not by themselves answer every question about treatment effect, clinical relevance, or safety.

The results do not establish the size of benefit for a particular participant. Group means can conceal variation in individual outcomes, and the registry record does not provide distributions or responder counts. It also does not report a threshold for a clinically meaningful change, so statistical separation from zero cannot be translated into a judgment about importance to patients.

The record does not identify the active control referred to in the brief summary or provide its numerical outcome. Nor does it clarify the mapping between the SPARC1310 intervention labels and S0597 outcome labels. The numerical comparisons can be described as placebo comparisons for the posted S0597-labeled groups, but should not be attributed more specifically than the record allows.

The findings are limited to the primary symptom-score endpoint and stated follow-up time. No secondary outcome results are posted, and longer-term outcomes are not described. Missing-data methods, analysis populations, dose amounts, and multiplicity handling are not reported in the registry record. The listed adverse-event counts offer limited safety information and lack event descriptions and statistical comparisons.

Accordingly, the posted results are evidence about the recorded mean symptom-score changes and their estimated contrasts under the analyses represented in the registry. They do not establish the original analysis strategy, settle the clinical significance of the differences, or support conclusions about outcomes not recorded.

16. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation needs both an effect estimate and a measure of uncertainty. The mean-difference estimates convey the direction and scale of the TNSS contrasts in score units, while the confidence intervals show a range of values compatible with the data under the interval procedure. Reading the point estimates without their intervals would hide uncertainty; reading p-values alone would hide the size and direction of the contrasts.

It also highlights the difference between statistical evidence and clinical meaning. The posted confidence intervals lie below zero, but the registry record does not define a threshold for a clinically meaningful TNSS change. Statistical separation from zero is not, on its own, evidence that the differences matter to patients or that every participant experienced a similar change.

The three comparisons against placebo make multiplicity a relevant issue. The p-values are explicitly unadjusted, and the registry does not report a correction or testing hierarchy. This matters because evidence across several comparisons is not interpreted in the same way as the result of a single prespecified test. The missing analysis-plan details limit certainty about how the posted results relate to the trial’s intended inferential framework.

The sample-size illustrations are another useful statistical distinction: planning calculations based on observed effects are not a record of the trial’s design assumptions or a measure of observed power. They show how the required per-arm size changes when the target effect is smaller, conditional on the stated planning assumptions.

Finally, the labels used for interventions and outcomes do not match transparently, while the summary refers to an active control that is not numerically represented in the listed outcomes. Clear correspondence between protocol arms and reported results is important for interpreting comparisons. The registry record supports careful description of the posted estimates, but leaves several aspects of their intended analysis and clinical context unresolved.

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 trial-specific limitations follow from the registry record. It reports the intervention names SPARC1310 I, II, and III, whereas the outcome groups are labeled S0597 Low Dose, Mid Dose, and High Dose. The record does not state explicitly that these pairs refer to the same groups. Dose amounts are not reported, so the dose labels cannot be linked to a quantitative regimen from this record alone.

The brief summary describes comparison with placebo and active control, but the posted outcome arms include placebo and three S0597-labeled groups without a separately identified active-control result. The identity and results of any active control are not reported in the registry record. This limits interpretation of the stated comparison objective.

The outcome reporting is narrow: one primary measure is listed and no secondary outcomes are posted. The primary measure is a combined symptom score, and separate results for congestion, rhinorrhea, nasal itching, or sneezing are not given. The record also does not state a clinically meaningful-change threshold. This constrains interpretation of both component symptoms and the practical importance of the average score differences.

Key analysis details are not reported, including the analysis population, missing-data handling, covariate adjustment, multiplicity procedure, and original sample-size rationale. The registry record also does not provide participant-level data or enough model detail to verify the reported least-squares means and contrasts independently. Consequently, the posted values support a description of the recorded comparisons, but not a complete reconstruction of the trial analysis.

Safety reporting is limited to affected counts and at-risk group sizes, without event terms or further characterization of other adverse events. Deaths are not reported in the registry record. These omissions should be distinguished from evidence that an event did not occur.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of SPARC1310 in Seasonal Allergic Rhinitis — NCT01940146.
• Registry record last updated 2019-05-03; status last verified 2019-05.
• Results first posted 2016-04-11.
• 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, randomized, double-masked, parallel phase 2 trial of SPARC1310 in seasonal allergic rhinitis, with enrollment reported as 222. The listed start is 2014-10 and primary completion is 2014-12.

The primary outcome is change in TNSS from baseline to Day 14. The posted arm means are -2.7 for placebo, -4.05 for S0597 Low Dose, -4.72 for S0597 Mid Dose, and -4.05 for S0597 High Dose. The posted placebo contrasts are negative, with confidence intervals entirely below zero and unadjusted p-values of 0.012, <0.001, and 0.013, respectively.

Serious adverse-event counts are zero in each listed group. Other adverse-event affected counts are 2, 3, 4, and 4 across placebo and the three SPARC1310-labeled groups. Deaths are not reported in the registry record. Intervention-to-outcome label mapping, active-control results, multiplicity handling, missing-data methods, analysis populations, and the original sample-size rationale are not reported in the registry record.