Efficacy and Safety of GSP 301 Nasal Spray in Children (Aged 6 to Under 12 Years) With Seasonal Allergic Rhinitis (SAR): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of GSP 301 Nasal Spray in Children (Aged 6 to Under 12 Years) With Seasonal Allergic Rhinitis (SAR) (NCT03463031), a randomized phase 3 study. The primary outcome is Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period.

2. Clinical Question

The study was designed to evaluate efficacy, safety, and tolerability in children with SAR. The primary question concerns change in a symptom score rather than a diagnosis or a count of clinical events. The score captures the reported severity of nasal symptoms, so the intended comparison is between average changes in that measure across the randomized groups.

The registry record identifies the outcome definition, the treatment period, and the population used for the primary efficacy analysis. It does not report group-specific baseline and follow-up means, change estimates, measures of uncertainty, or a test of the treatment-group contrast. The registry record therefore does not permit a quantitative answer to the primary question. The registered objective and outcome should be distinguished from the evidence available in the posted results: the objective describes what the study set out to evaluate, while the posted results do not report the primary efficacy comparison.

3. Trial Design

This was a phase 3, randomized, quadruple-masked, parallel-group study. It compared GSP 301 nasal spray with GSP 301 placebo nasal spray in pediatric subjects aged 6 to under 12 years with seasonal allergic rhinitis. The registry lists enrollment of 446 and identifies Glenmark Specialty S.A. as sponsor. Study start was recorded as 2018-03-16, primary completion as 2018-11-14, and status as completed.

Random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics at the point of assignment. Masking is intended to limit influences on treatment delivery, outcome assessment, and reporting when participants or study personnel do not know the assigned group. The registry identifies quadruple masking but does not specify in the record which roles were masked. The parallel-group model means participants were assigned to a treatment group rather than described as crossing between treatments.

The active nasal spray is described as a fixed-dose combination of olopatadine hydrochloride 665 μg and mometasone furoate 25 μg; the comparator is placebo nasal spray. The primary outcome is the average morning and evening subject-reported 12-hour reflective rTNSS change from baseline over the 14-day treatment period. The listed analysis population is the Full Analysis Set, defined by randomization, receipt of at least 1 dose of investigational product, and at least 1 post-baseline primary efficacy assessment.

The record also lists three secondary outcomes: change in average morning and evening subject-reported 12-hour instantaneous Total Nasal Symptom Score over the 14-day treatment period, change in the overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire score on Day 15, and change in average morning and evening subject-reported 12-hour reflective Total Ocular Symptom Score over the 14-day treatment period. The record lists 4 outcome measures and 4 analyses, but does not report the methods or results for the primary group comparison.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all subjects who are randomized and received at least 1 dose of IP and had at least 1 post-baseline primary 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 Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period, measured over Baseline and day 14.

The primary endpoint is change from baseline in the average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over the 14-day treatment period. It summarizes reported severity across four nasal symptoms: rhinorrhea, sneezing, nasal congestion, and nasal itching. Each symptom is rated from 0, meaning none, to 3, meaning severe; the symptom ratings are summed to give a total score ranging from 0 to 12. The unit is units on a scale, and the outcome is described as a mean with standard deviation.

A symptom score is used to represent symptom burden in a form that can be compared across treatment groups and over time. Reflective scoring asks subjects to report symptom severity over the preceding 12-hour period, and the endpoint combines morning and evening assessments. Change from baseline focuses the comparison on how scores shifted during treatment rather than on follow-up scores alone. The score's direction is interpretable: lower scores represent less reported symptom severity, while higher scores represent more severe symptoms.

The endpoint is subject-reported, so it records participants' assessments rather than an objective measurement of nasal physiology. Its interpretation depends on the reporting process and the definition of the scoring scale. Although the registry record describes the measure and timeframe, it does not report baseline or day 14 group means, the mean change in either group, or an estimated difference between groups. The clinical magnitude and statistical precision of the primary comparison are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and outcome definitions provide the framework for understanding what a statistical comparison would address. They do not, by themselves, give the comparison result. Statistical interpretation requires estimates from the groups, an estimate of the contrast, and information about uncertainty. Those primary outcome quantities are not reported in the registry record.

What does randomization contribute?

Randomization assigns participants to treatment groups using a chance-based process. Its statistical purpose is to reduce systematic differences between groups at assignment, supporting a fair comparison of outcomes. It does not guarantee that every characteristic will be identical between groups, and it does not prevent differences arising by chance. Masking can reduce the risk that knowledge of assignment influences care, assessment, or reporting. The registry describes the study as quadruple-masked but does not identify the masked roles in the record.

A parallel-group comparison assesses outcomes in groups assigned to different interventions. For the primary question, the relevant contrast would compare change in rTNSS in the GSP 301 group with change in rTNSS in the placebo group. A treatment contrast is not the same as a within-group change: improvement within a group could reflect the intervention, the passage of time, other influences, or measurement variation. The comparator provides the reference needed to interpret the relative change, but the estimated contrast is not reported in the registry record.

What does the endpoint measure?

The outcome is continuous and described as a mean with standard deviation. A continuous score can take values along a defined scale; here the rTNSS is constructed by summing ratings for four nasal symptoms. Each symptom receives a severity rating from 0 to 3, and the total score ranges from 0 to 12. The registry states that the primary outcome is the average morning and evening subject-reported 12-hour reflective score and that the timeframe is baseline and day 14, over the 14-day treatment period.

A mean describes the average score in a group, while a standard deviation describes the spread of scores around that mean. These answer different questions: the mean characterizes the group's central value, and the standard deviation describes participant-to-participant variability. Neither alone is the treatment effect. For an efficacy comparison based on change, the central estimate of interest is the between-group difference in change, with uncertainty around that estimate.

How should uncertainty be read?

In general, a confidence interval describes a range of values compatible with the data and the analysis under the method's assumptions. A narrow interval indicates greater precision than a wide interval, while an interval spanning effects in different directions may leave the comparative result uncertain. A p-value, when reported, describes how incompatible the observed data are with a specified null hypothesis under the statistical model; it does not measure the probability that a treatment works, nor does it show the clinical importance of an effect. The registry record does not report a confidence interval or p-value for the primary outcome.

Statistical significance and clinical importance are also distinct. A numerical difference can be estimated precisely yet be small in practical terms, or be potentially important but too imprecise to distinguish from no difference. Judging clinical importance would require a defensible interpretation threshold or other clinical context, neither of which is reported in the registry record. The score's defined range helps explain what is measured, but it does not by itself establish what change patients or clinicians would regard as important.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. When a model understates variability, standard errors may be too small and confidence intervals too narrow, making evidence appear more precise than it is. This issue is relevant to outcomes whose variability does not fit the assumptions of a chosen model. The primary outcome is a bounded symptom score, but the registry record does not report the analysis model or any assessment of its assumptions. It is therefore not possible to determine from the record whether over-dispersion was assessed or whether it affected inference.

What do sample-size illustrations mean?

In general, sample-size planning asks how many participants would be needed under chosen assumptions to detect a target effect with a stated error rate and power. The registry's planning illustration assumptions refer to the observed effect, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The listed convention is participants per arm for non-time-to-event outcomes. Such illustrations are not the study's observed result and must never be interpreted as observed power. The registry record does not report the trial's own sample-size justification. Since the primary effect estimate itself is not reported, a reader cannot use the record to assess how well a planning target corresponded to the observed comparative result.

Finally, the registry lists 4 outcome measures and 4 analyses, while the primary outcome is not reduced to a single reported comparison. The record does not explain the statistical model, covariate adjustment, handling of repeated observations, analysis hierarchy, or approach to multiple testing. These omissions constrain assessment of the assumptions and inferential procedures behind any unreported primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and three secondary outcomes, and reports 4 outcome measures and 4 analyses. Assessing several outcomes can raise a multiplicity question: if each is tested separately, the chance of at least one false-positive result can increase unless the analysis plan accounts for multiple comparisons. Common approaches include adjusting significance thresholds, defining a hierarchy of tests, or distinguishing confirmatory from exploratory analyses. These are general statistical options, not claims about the procedures used in this trial. The multiplicity strategy is not reported in the registry record.

The primary endpoint itself combines morning and evening assessments and is defined over the 14-day treatment period. The record does not report how the repeated assessments were incorporated into the analysis, whether any visits or time points were selected for inference, or whether there were planned subgroup analyses. It also does not report the treatment contrast, its uncertainty, or the test used for the primary outcome.

Missing-data handling is not described. The Full Analysis Set includes randomized subjects who received at least 1 dose of investigational product and had at least 1 post-baseline primary efficacy assessment. That definition does not state how partial observations, missing assessments, or discontinuations were treated in the analysis. The registry record does not report the number of participants contributing to the primary analysis or the reasons for missing outcome data. Because missingness can affect estimates when participants with missing observations differ from those with observed data, the analysis approach and its assumptions matter.

The record also does not describe sensitivity analyses intended to test whether conclusions depend on assumptions about missing values or model specification. Without those details, the robustness of any primary efficacy inference cannot be assessed from the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: meningitis viral (0.5%).

The registry lists serious adverse events for the GSP 301 and placebo groups. It reports 0 serious events among 225 participants at risk in the GSP 301 group and 1 serious event among 221 participants at risk in the placebo group. The listed serious-event term is meningitis viral, at 0.5%. The record reports 0 deaths in both groups. The other adverse-event category lists 0 events in both groups.

These figures are descriptive counts, not proof that a treatment caused or prevented an event. Serious adverse events are uncommon in the posted results, so the observed counts give limited information about comparative risk and cannot establish that no risk exists. The record does not report details about event timing, duration, outcome, relatedness to treatment, or the criteria used to classify events. It also does not provide a full account of non-serious adverse events in the registry record for this analysis.

The denominator described as at risk is the relevant group-specific count for interpreting each listed event figure. The reported 0.5% should be read as the registry's posted percentage for the serious-event term, not as an independently recalculated estimate. These safety findings are separate from the primary symptom endpoint and do not resolve the unreported efficacy comparison.

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

The record establishes that a completed, randomized, quadruple-masked, parallel-group phase 3 study compared GSP 301 nasal spray with placebo in children aged 6 to under 12 years with seasonal allergic rhinitis. It defines the primary endpoint as change in average morning and evening subject-reported 12-hour reflective rTNSS over the 14-day treatment period. It also identifies the Full Analysis Set and provides a limited set of serious adverse event figures.

What the record does not establish is the magnitude or direction of the primary treatment-group difference. The primary outcome results, including group changes and an estimated contrast, are not reported in the registry record. There is no reported confidence interval or significance test with which to assess precision or statistical compatibility with different possible effects. Therefore, the design and stated objective cannot be used as a substitute for the missing efficacy results.

The rTNSS is a symptom measure with a defined scoring range. Its scale gives a consistent way to record reported severity, but a change in score is not automatically a measure of clinical importance. Interpreting importance would require the observed treatment contrast and relevant clinical context. The record does not report a threshold for meaningful change or enough outcome data to characterize the observed change.

The safety counts likewise have a limited interpretation. They document the events recorded in the registry, including one serious event in the placebo group and none in the GSP 301 group, but they do not establish causality or exclude uncommon harms. The event counts are not a complete assessment of benefit and risk.

In general, randomized design and masking can strengthen a comparative study, but methodological strengths do not reveal an unreported result. The most defensible reading is that the registry documents the trial's design, intended primary measure, analysis-population definition, and selected safety information, while leaving the main comparative efficacy finding and important analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a well-defined research question and a reportable result. The registry specifies the population, randomized treatment comparison, masking, primary symptom scale, and treatment period. That information allows readers to understand what the study was intended to estimate. However, without the observed changes and the between-group estimate, the primary question remains unanswered by the registry record.

The endpoint also illustrates how a patient-reported measure becomes a statistical outcome. Several symptom ratings are combined into a total score, and average morning and evening reports are used to characterize the treatment period. A defined scale supports consistent measurement, but interpretation still depends on variability, missing observations, the analysis model, and the precision of the estimated contrast. Those elements are essential to judging how informative a result would be.

The study's randomized and masked design is relevant because it can support a less biased comparison, yet design labels alone do not show whether groups remained comparable in the analyzed data or how the analysis addressed repeated measures and missingness. The Full Analysis Set definition gives some clarity about who could contribute, while the treatment of incomplete data and the details of the statistical plan are not reported in the registry record.

Safety reporting provides another statistical lesson: rare events are difficult to compare when the observed counts are sparse. The reported serious-event figures should be read as descriptive, rather than as precise estimates of comparative safety. Taken together, this record shows why transparent reporting must include not only objectives and definitions but also estimates, uncertainty, analysis details, and clear explanations of safety findings. Without those results, readers can evaluate the structure of the question, but not the strength or size of the primary comparative evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report the primary efficacy results. It provides no group-specific baseline or follow-up summaries, mean changes, treatment contrast, confidence interval, or significance test for rTNSS. Consequently, neither effect size nor statistical precision can be assessed from the posted record.

The registry describes the primary analysis population as the Full Analysis Set, but does not report the number included in that analysis, the amount of missing outcome data, or how missing observations were handled. The definition requires at least 1 post-baseline primary efficacy assessment, so it does not by itself indicate how participants with partial follow-up contributed. The record also does not report sensitivity analyses for missing-data assumptions.

Important analytical details are not reported in the registry record, including the statistical model, any covariate adjustment, how repeated observations were handled, and the multiplicity strategy across listed outcomes. The record does not state whether subgroup analyses or interim analyses were planned or conducted. It also does not provide the trial's sample-size justification. These details are necessary to evaluate the analysis plan and the scope of inference, rather than to infer a result from the design.

The rTNSS is subject-reported, and its score is bounded from 0 to 12. The record defines how symptoms contribute to the total but does not report distributional summaries or how the analysis addressed the scale's properties. The posted safety information is limited to the listed categories and serious-event term; it does not give event-level timing, treatment relatedness, or a comprehensive adverse-event account. These limitations mean the registry information is insufficient for a full benefit-risk assessment or a precise interpretation of comparative efficacy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of GSP 301 Nasal Spray in Children (Aged 6 to Under 12 Years) With Seasonal Allergic Rhinitis (SAR) — NCT03463031.
• Registry record last updated 2019-10-08; status last verified 2019-09.
• Results first posted 2019-10-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03463031 is a completed phase 3, randomized, quadruple-masked, parallel-group study sponsored by Glenmark Specialty S.A. It enrolled children aged 6 to under 12 years with seasonal allergic rhinitis and compared fixed-dose GSP 301 nasal spray with placebo nasal spray. The recorded study start was 2018-03-16 and primary completion was 2018-11-14.

The primary outcome was change from baseline in average morning and evening subject-reported 12-hour reflective rTNSS over the 14-day treatment period. The registry defines the score using four nasal symptoms, each rated from 0 to 3, with a total range from 0 to 12. The Full Analysis Set required randomization, receipt of at least 1 dose, and at least 1 post-baseline primary efficacy assessment.

Primary efficacy estimates and analysis details are not reported in the registry record. The posted safety figures include 0 serious adverse events in the GSP 301 group and 1 in the placebo group, with 0 deaths in both groups. These counts are descriptive and do not establish causality.