This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Adult and Adolescent Subjects With Perennial Allergic Rhinitis (PAR) (NCT01133626), a randomized phase 3 study. The primary outcome is The 24-hour Serum Cortisol Weighted Mean After 42 Days of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01133626 |
| Phase | Phase 3 |
| Condition | Perennial Allergic Rhinitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 107 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Teva Branded Pharmaceutical Products R&D, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled adolescent and adult subjects aged 12 to 45 years with perennial allergic rhinitis (PAR). The primary outcome is described for the per-protocol population, which is not necessarily identical to the overall enrolled population. The registry does not report the eligibility criteria beyond the condition and age range in the study title.
Intervention
The intervention of interest was BDP HFA nasal aerosol at 320 µg/day. Participants self-administered four actuations, two per nostril, once each morning for 6 weeks (42 days). The study focused on whether this treatment was associated with a change in the 24-hour serum cortisol weighted mean, a measure related to HPA-axis function.
Comparator
The primary comparison was BDP HFA versus placebo nasal aerosol. The registry also lists a Placebo/Prednisone group as an active control for the cortisol outcome. That group received placebo HFA and prednisone capsules during week 6; it was not the comparator in the reported primary ANCOVA analysis.
Primary question
For the per-protocol population, what was the ratio of the 24-hour serum cortisol weighted mean at week 6 to its baseline value, and how did the BDP HFA group compare with placebo? The registry reports a geometric mean ratio for the week 6-to-baseline measure and an ANCOVA estimate comparing BDP HFA with placebo. The outcome was intended to evaluate effects on HPA-axis function, not clinical symptoms of rhinitis.
3. Trial Design
This was a randomized, triple-masked, parallel-group, phase 3 study with placebo and active control. The official title describes a 6-week study in adolescent and adult subjects aged 12 to 45 years with perennial allergic rhinitis. The registry lists enrollment as 107 and status as completed. It records a start in 2010-06 and primary completion in 2010-09.
The primary outcome compared BDP HFA 320 µg/day with placebo in the per-protocol population. Participants in the BDP HFA group self-administered four actuations of 80 µg once each morning for 6 weeks (42 days). Participants in the placebo group used four placebo actuations on the same schedule. During week 6, both groups also received placebo prednisone capsules as double-blind therapy for prednisone.
The active-control group used placebo HFA throughout treatment and took prednisone capsules during week 6 (days 36-42). This group is named Placebo/Prednisone in the outcome results. The registry lists it as an other pre-specified comparison, separate from the primary BDP HFA-versus-placebo comparison.
The registry lists arm-level primary outcome summaries for 48 participants in the BDP HFA group, 41 in the placebo group, and 9 in the Placebo/Prednisone group. These are outcome-analysis counts, not a replacement for the overall enrollment figure. The adverse-event record gives different at-risk counts for its groups, so the analyzed populations should be understood in relation to the particular outcome. The registry does not report details about who was masked, the randomization procedure, or allocation concealment.
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: During the 7 to 14 day Run-in Period (prior to randomization), participants self-administered a single-blind placebo nasal aerosol once daily in the morning.
Overall Study
| Stage | BDP HFA 320 µg/Day | Placebo | Placebo/Prednisone |
|---|---|---|---|
| STARTED | 50 | 46 | 11 |
| Safety Population | 50 | 46 | 11 |
| Per Protocol Population | 48 | 41 | 9 |
| COMPLETED | 49 | 41 | 9 |
| NOT COMPLETED | 1 | 5 | 2 |
Reasons for not completing this period:
| Reason | BDP HFA 320 µg/Day | Placebo | Placebo/Prednisone |
|---|---|---|---|
| Adverse Event | 0 | 1 | 0 |
| Withdrawal by Subject | 1 | 2 | 2 |
| Other | 0 | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Per protocol population
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.
| Characteristic | Unit | BDP HFA 320 µg/Day | Placebo | Placebo/Prednisone | Total |
|---|---|---|---|---|---|
| Participants analysed | 48 | 41 | 9 | 98 | |
| Age Continuous | years | 28.3 (SD 10.0) | 26.6 (SD 10.6) | 26.2 (SD 11.9) | 27.4 (SD 10.4) |
| Sex: Female, Male: Female | Participants | 25 | 22 | 7 | 54 |
| Sex: Female, Male: Male | Participants | 23 | 19 | 2 | 44 |
| Race/Ethnicity, Customized: Hispanic or Latino | participants | 18 | 17 | 2 | 37 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | participants | 30 | 24 | 7 | 61 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Asian | participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | participants | 7 | 2 | 1 | 10 |
| Race/Ethnicity, Customized: White | participants | 42 | 38 | 7 | 87 |
| Race/Ethnicity, Customized: Unknown or Not Reported | participants | 0 | 1 | 0 | 1 |
| Body Mass Index | kg/m^2 | 27.9 (SD 7.9) | 27.0 (SD 6.2) | 28.4 (SD 7.9) | 27.6 (SD 7.2) |
6. Primary Endpoint
The registry lists the primary outcome as The 24-hour Serum Cortisol Weighted Mean After 42 Days of Treatment, measured over Day 0 (Baseline), Day 42.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Standard Error |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the 24-hour serum cortisol weighted mean after 42 days of treatment. The registry describes measurements at Day 0 (Baseline) and Day 42, then reports the geometric mean ratio of week 6 to baseline. The primary comparison was between BDP HFA and placebo in the per-protocol population.
Cortisol is a hormone involved in HPA-axis function. In general, measuring cortisol over a 24-hour period can characterize hormone output across the collection period rather than relying on a single measurement. A baseline-to-follow-up ratio expresses the follow-up value relative to the participant's starting value on a multiplicative scale. This can be useful when an outcome is analyzed as a ratio and when proportional changes are of interest.
The endpoint is a laboratory measure related to the study's stated HPA-axis question. It is not a symptom score, a measure of allergic-rhinitis control, or a direct summary of every possible effect of treatment. The registry does not report the collection procedures, assay details, or the specific way individual measurements were combined into the weighted mean. Those details therefore cannot be used to interpret the result beyond the endpoint description in the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports arm-level geometric mean ratios of week 6 to baseline of 0.9 for BDP HFA, 0.95 for placebo, and 0.31 for Placebo/Prednisone. The corresponding recorded spreads are 1.04, 1.03, and 1.14; the outcome metadata labels the dispersion as standard error. These summaries describe the recorded arm results, but they are not the adjusted treatment comparison.
For the primary BDP HFA-versus-placebo comparison, the reported ANCOVA geometric mean ratio is 0.96, with a 95% confidence interval from 0.87 to 1.06. The ratio is the reported comparison estimate; the confidence interval expresses the uncertainty around that estimate under the analysis. It includes the value 1, which represents equal values on a ratio scale. The interval therefore does not isolate a difference in one direction from equality. The registry does not report a p-value for this analysis.
The analysis is classified in the registry as non-inferiority or equivalence. That classification alone does not establish that a non-inferiority or equivalence criterion was met. To assess such a conclusion, readers need the prespecified margin and the rule for interpreting the confidence interval. Neither is reported in the registry record. The estimate and interval can be described, but they do not support a complete independent judgment about whether a formal criterion was satisfied.
The Placebo/Prednisone arm has a lower reported geometric mean ratio than either primary-comparison arm. It is identified as an active control and an other pre-specified outcome, but the registry does not report an inferential comparison for it in the primary analysis. The arm-level result should not be treated as evidence about the primary contrast or as a formal test against placebo. Its reported analysis count is also smaller than those for the primary comparison.
The summaries concern the per-protocol population. They do not by themselves establish how the result would compare under other analysis populations or how departures from the protocol were handled. The record does not describe missing-data methods, model covariates, or the detailed analysis plan. The results are most precisely read as the posted arm summaries and ANCOVA estimate for the specified cortisol endpoint, with the limits on interpretation noted above.
9. Statistical Methods Explained
What does the geometric mean ratio represent?
In general, a geometric mean summarizes values on a multiplicative scale. A ratio compares a follow-up value with a reference value; in this study, the registry defines the reported arm measure as week 6 divided by baseline. A ratio of 1 represents no change on that ratio scale, a value below 1 represents a lower follow-up value relative to baseline, and a value above 1 represents a higher follow-up value relative to baseline. This interpretation concerns the scale of the measure, not the clinical importance of a change.
The posted arm values are 0.9 for BDP HFA, 0.95 for placebo, and 0.31 for Placebo/Prednisone. The arm-level display is not the same estimand as the reported ANCOVA comparison. An arm summary describes the group measure, whereas a between-group model estimates a contrast between treatment groups under the model used. The registry does not report enough model detail to reproduce or fully specify that contrast independently.
What does ANCOVA contribute?
In general, analysis of covariance (ANCOVA) estimates a group comparison while accounting for covariates specified in the model. Covariate adjustment can make the comparison conditional on measured characteristics and can affect the estimate and its precision. The registry names ANCOVA for the comparison of BDP HFA and placebo, but does not identify the covariates, their coding, or the model scale. It is therefore not possible to say from this record which adjustments were made, or to reconstruct the model from the arm-level summaries.
The reported ANCOVA estimate is a geometric mean ratio of 0.96. It is accompanied by a 95% confidence interval from 0.87 to 1.06. In general, a confidence interval represents a range of estimates compatible with the data and the statistical model at the stated confidence level. It describes uncertainty; it does not assign a probability that the true value lies in the particular interval after the data have been observed. Its interpretation also relies on the model and analysis assumptions.
Because this estimate is a ratio, the value 1 is the reference for equality between the compared quantities. The reported interval extends across that reference. The record gives no p-value, so one should not substitute an unreported significance test for the interval or infer a specific p-value from it.
How should the non-inferiority or equivalence label be read?
The registry categorizes the reported comparison as non-inferiority or equivalence. In general, a non-inferiority analysis asks whether an intervention is not worse than a comparator by more than a prespecified margin; an equivalence analysis asks whether the comparison lies within prespecified bounds. Those conclusions depend on the margin or bounds and the prespecified decision rule, not merely on whether a confidence interval includes 1. The registry does not report the margin, bounds, or decision rule. The classification is useful context for the intended analysis, but it is insufficient to determine the formal result.
More generally, non-inferiority and equivalence conclusions can depend on the analysis population and protocol deviations as well as the statistical model. The primary outcome is explicitly described for the per-protocol population. The registry does not provide a complementary intention-to-treat result or a sensitivity analysis, so the robustness of the conclusion across analysis populations cannot be assessed from this record.
What do the arm-level spreads tell the reader?
The outcome metadata labels the dispersion as standard error, and the arm summaries give spreads of 1.04, 1.03, and 1.14. A standard error generally describes the estimated precision of a statistic, rather than the spread of individual participant measurements. The record does not give arm-level confidence intervals or a fuller description of how these spread values were calculated. They should therefore be read as the displayed dispersion statistics, not as a substitute for the confidence interval for the adjusted comparison.
For data that vary more than a simple model assumes, general methods may need to account for over-dispersion to avoid understating uncertainty. The endpoint is a continuous cortisol measure summarized as a geometric mean ratio, and the registry does not identify an over-dispersion model. No claim about over-dispersion or the need for a particular model can be made from the posted information.
What can planning illustrations tell us?
General sample-size planning illustrations translate an assumed effect and statistical design into a planning requirement. The illustrations associated with this analysis are described as based on the observed effect, a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence of the trial's original design or justification.
Such planning calculations are not observed power. Observed power is not a substitute for interpreting the confidence interval and estimate from the completed study. The registry does not report the original sample-size justification, and no particular planning count should be treated as the enrollment target or as a feature of the trial protocol. For time-to-event outcomes, planning calculations can be framed in terms of events; this cortisol outcome is not identified as a time-to-event endpoint.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANCOVA | geometric mean ratio 0.96 | 0.87 to 1.06 | not reported |
The sponsor-reported primary analysis is the ANCOVA estimate: a geometric mean ratio of 0.96 for BDP HFA compared with placebo, with a 95% confidence interval from 0.87 to 1.06. The registry does not report a p-value for this comparison. The arm-level summaries are not themselves a recalculation of the adjusted ANCOVA result, because they do not supply the model specification or covariates.
A separate recalculated estimate is not reported in the registry record. Without a reported recalculation and the details needed to reproduce the ANCOVA, there is no independent numerical estimate to set beside the sponsor's analysis. The arm summaries provide context for the outcome, but should not be used to invent an adjusted comparison or infer the sponsor's model. The appropriate interpretation of the primary comparison therefore rests on the sponsor-reported estimate and confidence interval, alongside the limitations of the registry entries.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and one reported analysis, and it lists zero secondary outcomes posted. This describes what is posted in the record; it does not establish that no additional outcomes were measured or considered. The record does not report a multiplicity plan, such as whether or how testing across outcomes or comparisons was controlled. Because the primary analysis is classified as non-inferiority or equivalence, the missing margin and decision rule are also important omissions for interpretation.
The primary outcome population is the per-protocol population. The registry does not report how protocol deviations were defined, how participants were assigned to analysis populations, or whether another population was used for a sensitivity analysis. It also does not describe how missing cortisol measurements were handled, whether imputation was used, or how participants with incomplete measurements contributed to the analysis. Those procedures are not reported in the registry record.
The record gives the primary outcome timeframe as Day 0 (Baseline) and Day 42. The available description does not provide the timing or completeness of individual measurements, or reasons for missing data. A record note states that values are missing or not estimable for a two-arm comparison for another endpoint; it does not specify a missing-data method for the primary cortisol result. That note should not be taken as an explanation of the primary analysis.
The available population and analysis information is therefore limited to the per-protocol description, the posted arm summaries, and the reported ANCOVA contrast. Details about the statistical analysis plan, covariate selection, interim analyses, and multiplicity handling are not reported in the registry record.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BDP HFA 320 µg/Day | 0 | 50 | 0.0% |
| Placebo | 0 | 46 | 0.0% |
| Placebo/Prednisone | 0 | 11 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BDP HFA 320 µg/Day | 3 of 50 |
| Placebo | 3 of 46 |
| Placebo/Prednisone | 5 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BDP HFA 320 µg/Day | Placebo | Placebo/Prednisone |
|---|---|---|---|---|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 2 of 50 | 1 of 46 | 1 of 11 |
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | 1 of 50 | 2 of 46 | 1 of 11 |
| Gastroenteritis | Infections and infestations | 0 of 50 | 0 of 46 | 1 of 11 |
| Blood oestrogen increased | Investigations | 0 of 50 | 0 of 46 | 1 of 11 |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 0 of 50 | 0 of 46 | 1 of 11 |
The serious adverse-event summaries report zero events in the BDP HFA group among 50 participants at risk, zero in the placebo group among 46 participants at risk, and zero in the Placebo/Prednisone group among 11 participants at risk. These are the counts recorded for the listed groups. The registry does not provide serious adverse-event terms, and the list of top serious terms is empty.
Zero recorded serious adverse events in these groups means that none are listed for the reported at-risk populations during the study record's safety reporting. It does not establish that the risk is zero or rule out uncommon events. The record does not give confidence intervals for these safety counts, detailed exposure information, or a description of how adverse events were collected.
The registry also lists other adverse events affecting 3 participants in the BDP HFA group, 3 in the placebo group, and 5 in the Placebo/Prednisone group. These are separate from serious adverse events and should not be combined with them. Death counts are recorded as null, not as zero; deaths are therefore not reported in the registry record. Safety summaries are descriptive and do not provide a formal between-group comparison.
13. What the Result Does, and Does Not, Mean
The result addresses a specific statistical and physiological question: the week 6-to-baseline geometric mean ratio for the 24-hour serum cortisol weighted mean, with a primary comparison of BDP HFA and placebo in the per-protocol population. The sponsor-reported ANCOVA estimate is 0.96, and its 95% confidence interval is 0.87 to 1.06. The interval gives a sense of precision around the reported comparison and includes the ratio reference value of 1.
The registry's non-inferiority or equivalence label describes the analysis category, but the necessary margin and decision rule are not reported. The numerical estimate and confidence interval therefore do not, on their own, settle whether the trial met a formal non-inferiority or equivalence criterion. The record also does not provide a p-value or enough model detail to independently reproduce the analysis.
This outcome is a measure related to HPA-axis function. It is not a direct measure of symptom relief, day-to-day functioning, or every possible effect of treatment. The study's stated purpose was to evaluate effects on HPA-axis function, and the posted primary result should be interpreted within that scope. It cannot by itself answer broader questions about rhinitis outcomes or longer-term effects.
The arm-level results and safety counts also have defined limits. The outcome summaries use the per-protocol population, while the adverse-event summaries list different at-risk counts. The record does not describe missing-data handling, a complementary analysis population, or the full statistical plan. These limitations do not erase the reported estimate; they define what can be concluded from the registry record and what remains uncertain.
14. Why This Trial Matters Statistically
This trial illustrates why an endpoint, an arm summary, and a treatment comparison are not interchangeable. The primary endpoint is a week 6-to-baseline geometric mean ratio for a cortisol measure. The arm-level summaries describe the groups, while the ANCOVA estimate is the reported between-group comparison. Distinguishing those quantities prevents readers from treating separate summaries as though they were an adjusted treatment effect.
The confidence interval is also central to interpretation. The point estimate alone gives no account of precision, while the interval makes uncertainty visible on the ratio scale. In this record, the interval includes the equality reference. At the same time, the non-inferiority or equivalence classification cannot be fully assessed without the margin and decision rule. The study is a useful example of why statistical labels and numerical results need the accompanying design criteria.
Finally, the record demonstrates the importance of matching conclusions to the analysis population and endpoint. The primary result is for the per-protocol population and concerns HPA-axis function, not a broad clinical outcome. A careful reading keeps those boundaries in view and distinguishes reported results from methods or details that are not available.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report the non-inferiority or equivalence margin, the decision rule, or a p-value for the primary comparison. It names ANCOVA but does not describe the covariates, model specification, or analysis scale in sufficient detail for an independent reconstruction. The arm-level summaries include dispersion values but do not supply arm-level confidence intervals.
The primary endpoint is reported for the per-protocol population. The record does not give details about protocol deviations, the intention-to-treat population, sensitivity analyses, or the method used to handle missing cortisol measurements. Although the listed group counts for the primary outcome and safety outcome are available, the record does not explain the differences in analysis populations or provide participant-level flow information.
The outcome description identifies the measurement period and ratio but does not give assay details, collection procedures, or the calculation steps for the 24-hour weighted mean. The record also does not report a multiplicity plan, interim-analysis information, or the original sample-size justification. Planning illustrations based on the observed effect are not the trial's original design justification and are not observed power.
Safety reporting is limited to the listed counts and at-risk groups. Death counts are null, and no serious adverse-event terms are listed. Detailed event definitions, follow-up exposure, and inferential safety comparisons are not reported. These omissions limit assessment of precision, reproducibility, and the scope of conclusions that can be drawn from the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Hypothalamic-Pituitary-Adrenal (HPA) Axis Study in Adult and Adolescent Subjects With Perennial Allergic Rhinitis (PAR) — NCT01133626.
- Registry record last updated 2012-07-04; status last verified 2012-05.
- Results first posted 2012-07-04.
- 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.
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19. Record Summary
NCT01133626 is a completed, randomized, triple-masked, parallel-group phase 3 study of BDP HFA nasal aerosol in adolescents and adults aged 12 to 45 years with perennial allergic rhinitis. The study examined the 24-hour serum cortisol weighted mean at baseline and Day 42, with the primary comparison between BDP HFA 320 µg/day and placebo in the per-protocol population.
The reported ANCOVA geometric mean ratio is 0.96, with a 95% confidence interval from 0.87 to 1.06. The registry classifies the analysis as non-inferiority or equivalence but does not report the margin or decision rule. Arm-level summaries are also posted for the Placebo/Prednisone active-control group. The record does not provide detailed model specifications, missing-data procedures, or a multiplicity plan, which limits independent assessment of the analysis.