A Study to Assess the Potential for Airway Sensitivity Reactions With Propellants HFA-152a (Test) and HFA-134a (Reference) Administered Via Pressurized Inhalers in Adults With Mild Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Potential for Airway Sensitivity Reactions With Propellants HFA-152a (Test) and HFA-134a (Reference) Administered Via Pressurized Inhalers in Adults With Mild Asthma (NCT06702462), a randomized phase 1 study. The primary outcome is Percentage Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at 15 Minutes Post-dose.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, controlled, single-dose, 2-way crossover Phase 1 study. It compared HFA-152a, the test propellant, with HFA-134a, the reference propellant, in pressurized metered dose inhalers. The study enrolled adults aged 18-45 with mild asthma and had a reported enrollment of 20.

A crossover design means participants receive the study conditions in a sequence, so each participant can contribute observations under more than one condition. The registry record lists the sequences as HFA-152a followed by HFA-134a, and HFA-134a followed by HFA-152a. In principle, this design allows a comparison that accounts for within-participant responses. The interval between doses, any washout procedures, and the precise timing and conduct of sequence allocation are not reported in the registry record.

Double-blind masking means the study was recorded as masking participants and relevant study personnel to treatment assignment. The registry record does not specify which personnel were masked or how masking was maintained. The sponsor was GlaxoSmithKline. The study start date was 2025-03-11, primary completion was 2025-06-04, and status is completed.

The arm summaries list Salbutamol HFA-152a (Test) and Salbutamol HFA-134a (Reference). Each listed arm has 19 participants for the primary outcome. In a crossover study, arm counts should not be read as independent participant groups: the registry record describes treatment sequences, and the participant-level overlap is not presented in the arm summaries.

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.

Period 1

Reasons for not completing this period:

Period 2

Analysis population for the primary outcome, as defined in the registry: Fully complaint analysis set (FCAS) population included all participants who were able to adhere to the dose of study intervention as prescribed and completed the 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 Percentage Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at 15 Minutes Post-dose, measured over Baseline (Day 1, pre-dose) and at 15 minutes post-dose.

The primary endpoint was percentage change from baseline in forced expiratory volume in 1 second (FEV1) at 15 minutes after dosing. FEV1 is the volume of air that can be forcibly exhaled in one second after a deep breath, measured by spirometry. The baseline was defined as the latest pre-dose assessment with a non-missing value, including assessments from unscheduled visits.

FEV1 is used in this study as a measurable indicator of airway function. Because the study question concerns the potential for airways to tighten after inhalation, a short-term change in FEV1 provides a physiological measure relevant to that question. The endpoint is a percentage change from each participant’s baseline rather than an absolute volume, allowing the result to be expressed relative to the participant’s own pre-dose measurement.

The registry record reports least-squares means and 95% confidence intervals for the two treatment conditions. The primary endpoint is specifically the assessment at 15 minutes; it should not be confused with secondary FEV1 outcomes at other times or with the secondary area-under-the-curve measure. The primary analysis population was the FCAS, comprising participants who adhered to the prescribed dose and completed the study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: percentage change in FEV1 at 15 minutes. A continuous measure can take a range of values, so the analysis describes the average response and its uncertainty rather than counting participants only as having or not having an event. The registry reports least-squares means for each condition and a net mean difference from a mixed models analysis.

What does the least-squares mean represent?

A least-squares mean is a model-based estimate of an average. It can account for terms included in the fitted model, rather than being only the arithmetic average of observed values. The registry record identifies the analysis as a mixed models analysis, but does not report the model formula, the included terms, the covariance structure, or the estimation details. Consequently, the exact adjustment represented by these least-squares means cannot be reconstructed from the registry record.

The posted treatment-specific estimates are -0.37 for the test condition and -0.6 for the reference condition. Their respective 95% confidence intervals are -3.42 to 2.68 and -3.65 to 2.44. The model-based net mean difference is 0.233. These estimates answer related but distinct questions: each treatment-specific estimate describes a modeled mean percentage change, while the net difference summarizes the modeled contrast between conditions.

Why use a mixed model in a crossover study?

General statistical explanation: observations from the same participant tend to be related. A mixed model can represent that dependence and can include participant-level structure, alongside treatment and other model terms. Accounting for within-participant correlation can make the uncertainty estimate more appropriate than treating every measurement as independent. The registry record names a mixed models analysis, but does not state its exact structure, so the particular way this analysis handled participant, sequence, period, or other effects is not reported in the registry record.

In a crossover design, the comparison can benefit from each participant serving as their own reference. That benefit depends on the design and analysis being suitable, including how potential period or carryover effects are handled. The registry record does not report the washout interval, the model terms for sequence or period, or whether carryover was assessed. Those details should not be inferred from the study’s crossover label alone.

How should the confidence interval be read?

A confidence interval describes the uncertainty around an estimate under the statistical model and its assumptions. The reported 95% confidence interval for the net mean difference extends from -3.605 to 4.070. The values at its limits mark a range of estimates reasonably compatible with the observed data under that model. It is not a guarantee that the true effect lies within that particular interval, and it does not show that all values in the interval are equally plausible.

The interval crosses zero, which is the value corresponding to no mean difference on the contrast scale. This is consistent with the reported p-value of 0.905 for testing a null of zero difference, but that test is not the same as a non-inferiority test. Non-inferiority requires a prespecified margin. Because the margin is not reported in the registry record, neither the interval nor the p-value establishes whether the non-inferiority criterion was satisfied.

What does the p-value add?

General statistical explanation: a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that null model and its assumptions were correct. It is not a measure of clinical importance, does not quantify the probability of no effect, and cannot replace the estimated difference and confidence interval. In this record, the p-value is reported as 0.905 alongside the model-based difference and its interval.

The registry record reports one analysis for the primary comparison. It does not report the testing hierarchy, whether the analysis was prespecified in the protocol, or whether any adjustment for multiple testing was planned. The study also lists several secondary outcomes, so the interpretation of any secondary p-values would depend on the multiplicity plan, which is not reported in the registry record.

What information is needed to evaluate the analysis fully?

Evaluation of the model depends on details beyond the estimate and interval. The registry record does not report the non-inferiority margin, the full model specification, treatment sequence and period terms, assumptions and diagnostics, or a detailed account of missing outcome data. The primary analysis population is described as participants who adhered to the prescribed dose and completed the study, but the record does not give the reasons for exclusions or a separate analysis of all randomized participants. These gaps limit independent assessment of the analysis choices and of how robust the result is to alternative assumptions.

10. Analyses Reported by the Sponsor

The registry record reports the sponsor’s mixed-model estimate as a net mean difference of 0.233, with a 95% confidence interval from -3.605 to 4.070 and p = 0.905. This model-based comparison is the primary inferential result available for the endpoint. The treatment-specific least-squares means and their confidence intervals provide useful context, but they do not contain all the information needed to reproduce the mixed-model contrast.

In particular, a crossover comparison depends on the paired participant-level data and their covariance, as well as the model specification. Those details are not reported in the registry record. The posted arm summaries alone therefore do not permit an independent reconstruction of the sponsor’s mixed-model calculation. The registry record does not identify a discrepancy between the reported arm summaries and the sponsor’s analysis. Where a recalculation and sponsor analysis conflict, the sponsor’s own analysis takes precedence; no conflicting recalculation is identified in this record.

The sponsor’s result should be read with the uncertainty interval and the unreported non-inferiority margin in mind. It is not possible to verify the non-inferiority decision from the estimate and p-value alone. The margin and the full statistical plan are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is clearly identified as percentage change from baseline in FEV1 at 15 minutes after dosing. The registry record also lists secondary outcomes: FEV1 area under the curve from time zero to 15 minutes; percentage change from baseline in FEV1 at 5, 60, and 180 minutes; the number of participants with a percentage decrease in FEV1 of <-15% at specified timepoints; and adverse events and serious adverse events. The number of secondary outcomes posted is 4.

When a study evaluates multiple outcomes or timepoints, the chance of at least one apparently notable finding can increase if each is tested separately without a plan to account for multiplicity. General statistical explanation: a prespecified testing hierarchy or multiplicity adjustment can help control the interpretation of a family of tests. The registry record does not report whether such a plan was used, which outcomes were included in any testing family, or whether secondary analyses were confirmatory or exploratory. The primary analysis result should therefore remain distinct from any conclusions based on secondary outcomes.

The primary population is described as the FCAS, defined as participants able to adhere to the prescribed dose and complete the study. The record does not report the number excluded from that population or the reasons for exclusion. Although the enrollment is 20 and the primary outcome arm summaries each list 19, the registry record does not explain the relationship between these counts. The per-arm summaries in a crossover trial should not be interpreted as separate randomized groups without participant-level information.

The registry record does not report how missing primary outcome measurements were handled, whether imputation was used, or whether sensitivity analyses assessed alternative missing-data assumptions. It also does not report a detailed participant flow for the primary analysis population. These omissions make it difficult to judge how exclusions or missing measurements may have influenced the estimate.

The non-inferiority margin, sample-size justification, interim analyses, and full statistical analysis plan are not reported in the registry record. In particular, the absence of the margin prevents assessment of the formal non-inferiority criterion. These are separate uncertainties from the reported confidence interval, which describes sampling uncertainty under the fitted model.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The posted safety figures report zero serious adverse events among 20 participants at risk for Salbutamol HFA-152a (Test), and zero among 19 at risk for Salbutamol HFA-134a (Reference). The record also reports one other adverse event in each condition. No deaths are reported in either condition.

These counts describe the events recorded during this study; they should not be treated as proof that serious adverse events cannot occur. A study of this size and single-dose design provides limited information about uncommon events or safety with longer exposure. The registry record does not identify the terms for the other adverse events, and no top serious-event terms are listed. It also does not provide a detailed account of event severity, timing, relationship to treatment, or the method used to attribute events to a condition.

Because the design is crossover, participants may contribute safety observations under more than one condition. The at-risk counts are presented separately by condition, and should not be added to infer the number of distinct participants. The zero serious-event counts are descriptive observations for the recorded follow-up, not a statistical demonstration of equal safety between propellants.

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

The posted results describe a small, single-dose crossover comparison of two propellants in adults with mild asthma. For the primary outcome, the model-based net mean difference was 0.233, with a 95% confidence interval from -3.605 to 4.070. The interval includes zero and extends in both directions, so the estimate is uncertain about the direction and magnitude of the difference. The reported p-value was 0.905.

These results do not, on their own, establish equivalence or non-inferiority. Non-inferiority is assessed against a prespecified margin, and that margin is not reported in the registry record. A non-significant test of zero difference is not a substitute for a non-inferiority analysis. The reported estimate also should not be interpreted as evidence that the conditions have identical effects.

The endpoint measures short-term change in FEV1 at 15 minutes after dosing. It does not directly establish what happens with repeated use, over longer periods, or for outcomes beyond the measured spirometric and adverse-event assessments. The study’s adult mild-asthma population also defines the population directly represented by this result; the record does not establish how well it applies to other populations.

The safety record reports zero serious adverse events for each condition and one other adverse event for each. These observations are descriptive and do not settle comparative safety, particularly for uncommon events. Overall, the registry result is a model-based estimate with a confidence interval, rather than a definitive statement of equality, non-inferiority, or broader clinical outcomes.

14. Why This Trial Matters Statistically

This trial raises a statistical question that is easy to misread: a non-inferiority study is not judged by whether a conventional test finds a difference. The decision depends on whether the confidence interval excludes an unacceptable loss, as defined by a prespecified margin. The registry record reports the treatment contrast and its 95% confidence interval, but not the margin. This illustrates why an estimate and p-value alone may be insufficient to interpret the stated trial objective.

The crossover design is also central to understanding the comparison. Repeated conditions within participants can allow a direct paired comparison, but valid interpretation depends on the model representing the within-participant structure and relevant effects. The registry record names a mixed models analysis, while leaving its exact specification unreported. This distinction matters: knowing the model family is useful, but does not reveal all the assumptions behind the estimate or its uncertainty.

The primary outcome is a continuous physiological measure, with treatment-specific least-squares means and a model-based contrast. Keeping those quantities separate helps avoid treating arm summaries as if they alone determine the crossover comparison. The reported interval conveys more about precision than the p-value alone, and its span should be considered alongside the point estimate.

Finally, the safety counts and primary outcome address different questions. Zero recorded serious adverse events is a descriptive finding, while the primary analysis concerns short-term FEV1 change. Neither alone answers every question about airway sensitivity, repeated exposure, or less common harms. The registry record supports a focused statistical reading of this trial, while its unreported design and analysis details limit broader interpretation.

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 most important limitation for interpreting the stated non-inferiority objective is that the non-inferiority margin is not reported in the registry record. Without it, the formal decision rule cannot be checked against the reported confidence interval. The full statistical plan, including the rationale for the margin and the sample-size justification, is also not reported in the registry record.

Although the primary analysis is identified as a mixed models analysis, the model specification is not reported. The record does not describe the terms included, covariance assumptions, treatment of sequence or period, or assessment of carryover. The crossover structure makes these details relevant to understanding how the comparison and its uncertainty were obtained. The washout interval is also not reported in the registry record.

The primary analysis population is described as participants who adhered to the prescribed dose and completed the study. The record does not explain how many participants were excluded from this population, why exclusions occurred, or how missing endpoint observations were handled. It does not report sensitivity analyses or a separate analysis using a different population definition. The relationship between the enrollment of 20 and the arm summaries of 19 is not explained.

The endpoint is a short-term spirometric measurement after a single dose. The record does not establish longer-term outcomes or effects of repeated exposure. The reported safety counts are descriptive, and event terms and detailed attribution information for the other adverse events are not reported in the registry record. These limits restrict conclusions about uncommon or longer-term safety outcomes.

The study concerns adults aged 18-45 with mild asthma. The result should be interpreted in that study context; broader applicability is not established by the registry record. Secondary outcome results and details of any multiplicity strategy are also not reported in the posted results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess the Potential for Airway Sensitivity Reactions With Propellants HFA-152a (Test) and HFA-134a (Reference) Administered Via Pressurized Inhalers in Adults With Mild Asthma — NCT06702462.
• Registry record last updated 2026-08-21; status last verified 2026-06.
• Results first posted 2026-08-21.
• 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.

19. Record Summary

This completed Phase 1 study compared Salbutamol HFA-152a (Test) with Salbutamol HFA-134a (Reference) in a randomized, double-blind, controlled, single-dose, 2-way crossover design. It enrolled adults aged 18-45 with mild asthma. The primary endpoint was percentage change from baseline in FEV1 at 15 minutes after dosing.

The sponsor’s mixed-model analysis reported a net mean difference of 0.233, with a 95% confidence interval from -3.605 to 4.070 and p = 0.905. The non-inferiority margin is not reported in the registry record, so the formal non-inferiority criterion cannot be assessed from these results alone.

The record reports zero serious adverse events in each condition and one other adverse event in each. The start date was 2025-03-11, primary completion was 2025-06-04, and the sponsor was GlaxoSmithKline.