Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients (NCT01577082), a randomized phase 3 study. The primary outcome is Change From Baseline to the Average of the Entire Treatment Period Reported, in the Average Pre-dose Morning Peak Expiratory Flow (PEF).

2. Clinical Question

The question concerns a measured lung-function outcome during treatment, rather than a direct comparison of every possible asthma outcome. The record also lists secondary measures involving symptoms, rescue medication, peak-flow variability, symptom-free days and asthma exacerbations. Those measures can add context, but they do not replace the prespecified primary question.

3. Trial Design

The registry record describes a phase 3, randomized, quadruple-masked, parallel-group study. Its official title identifies it as multinational, multicentre, double-blind and double-dummy. The trial compared CHF 1535 200/6µg pMDI with beclomethasone dipropionate HFA pMDI over a 12-week treatment period. The record lists an enrollment of 542 and a status of completed.

Eligible participants were adults with asthma not adequately controlled on high-dose inhaled corticosteroids or medium-dose inhaled corticosteroids plus long-acting β2 agonists. The record identifies asthma as the condition under study and Chiesi Farmaceutici S.p.A. as sponsor. The study start is listed as 2012-04-20, and primary completion as 2012-11-29.

The intervention was a fixed-dose combination of beclomethasone dipropionate and formoterol fumarate, while the comparator was beclomethasone dipropionate HFA. The stated daily doses were 800 µg of beclomethasone dipropionate and 24 µg of formoterol fumarate for the combination, and 800 µg of beclomethasone dipropionate for the comparator. The registry record does not report the complete administration schedule for the combination arm.

For the primary outcome, the intent-to-treat population was defined as randomized participants who received at least one administration of study drug and had at least one post-baseline efficacy evaluation. The record states that a maximum of 182 participants in the CHF 1535 group and 170 in the BDP group were analyzed for that outcome. These analysis-population counts are not the same as the overall enrollment figure. The original sample-size justification and the trial’s design assumptions are not reported in the registry record.

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: After enrollment, participants entered a 2-week open-label run-in phase with beclomethasone dipropionate (BDP) pMDI at 800 µg/day (4 puffs morning/evening). During this phase, compliance, lung function, and asthma control were monitored. At Visit 2 (Week 0), eligible patients were randomized into two treatment groups for the 12-week double-blind phase.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population: all randomised patients who received at least one administration of the study drug and with at least one available evaluation of efficacy after the baseline. A maximum of 182 patients for CHF1535 and 170 for BPD were analyzed.

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.

Population: The Intention-to-treat (ITT) population included all randomized patients who received at least one dose of the study medication and had at least one post-baseline efficacy assessment

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to the Average of the Entire Treatment Period Reported, in the Average Pre-dose Morning Peak Expiratory Flow (PEF), measured over Baseline and Throughout the 12-week treatment period.

The primary endpoint was change from baseline in average pre-dose morning peak expiratory flow, or PEF, across the entire treatment period. PEF measures the maximum speed of air exhaled during a forceful breath and is used as an indicator of lung function. The endpoint was reported in L/min. The registry record states that higher PEF values indicate better lung function, while a decline suggests worsening obstruction.

Participants recorded morning pre-dose PEF each day using an electronic peak flow meter, with results transmitted to an e-diary. Baseline was measured during a 2-week run-in period. Measurements were taken before study medication, using a standardized procedure in which the highest value from three maneuvers was recorded. The device gave feedback when it detected specified errors or inconsistent readings.

Using the average across the treatment period summarizes repeated daily measurements rather than relying on a single reading. A change-from-baseline outcome compares each participant’s follow-up experience with their own baseline value, and the between-group contrast addresses whether those changes differed between randomized groups. This is a lung-function endpoint; it does not by itself describe symptoms, exacerbations, rescue medication use or every other aspect of asthma control.

7. Results Posted in the Registry

• BDP 100µg - ITT: mean -3.63 versus 16.45 on control; difference -20.08 (95% CI -28.20 to -11.96), standardized effect d = -0.51; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline to Week 12 (Visit 8) in ACQ Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • BDP 100µg - ITT: mean -0.64 versus -0.63 on control; difference -0.01 (95% CI -0.15 to 0.13), standardized effect d = -0.02; z-test p = 0.888.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BDP 100µg - ITT and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients With Asthma Exacerbations

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • BDP 100µg - ITT: 3.4% (6/175) versus 2.2% (4/184) on control; risk difference 1.3 percentage points (95% CI -2.2 to 4.7), risk ratio 1.58 (0.45–5.49); unadjusted two-proportion z-test p = 0.470.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BDP 100µg - ITT and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a broad set of secondary outcomes covering lung function, rescue medication use, symptom scores, symptom-free days and asthma exacerbations. The secondary results are not all the same type of measure: some are continuous changes, while the exacerbation outcome is a participant count. These outcomes offer complementary views of asthma control and activity, but they do not measure the same construct as average morning PEF.

The available numerical secondary results do not provide a uniform pattern of clear differences between groups. The ACQ analysis does not show a statistically clear between-group contrast, and the recalculated exacerbation comparison is uncertain. These findings do not negate the primary PEF result; they address different outcomes with different scales and information. Nor should the primary result be taken to imply that every secondary measure changed in the same direction or to the same degree.

Unadjusted secondary findings generally carry less weight than the primary result when many outcomes are examined. The more outcomes tested, the greater the chance that some results may appear noteworthy by chance, unless the analysis accounts for multiplicity. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. That uncertainty is relevant when assessing isolated secondary findings, particularly where the number of analyses recorded is 78.

The registry record states that 14 secondary outcomes were posted, but it does not provide numerical results for every outcome in the summaries available for interpretation. Consequently, the overall secondary pattern can only be described at a broad level. No conclusion about an unreported secondary outcome should be inferred from the primary endpoint or from the subset of secondary results with numerical summaries.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline to Each Inter-visit Period in Average Pre-dose Morning Peak Expiratory Flow (PEF)
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Pre-dose Evening PEF
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Daily PEF Variability
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Use of Rescue Medication
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Percentage of Rescue Use-free Days
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Day-time Asthma Symptom Score
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Total Night-time Asthma Symptom Score
• Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Percentage of Asthma Symptom-free Days

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it measures change in average PEF in L/min. For each group, the registry reports a mean and standard deviation. The mean describes the group’s average change, while the standard deviation describes how spread out individual measurements are around that mean. A standard deviation is not a confidence interval for the group mean and does not, by itself, quantify uncertainty in the between-group comparison.

What does the between-group estimate represent?

The unadjusted recalculation compares the two posted group means. Its contrast is stated as BDP minus CHF 1535, so its negative sign indicates a lower mean change in the BDP group under that ordering. The registry-reported ANCOVA estimate uses the opposite ordering, as indicated by the positive result for the CHF 1535 versus BDP comparison. A change in contrast order changes the sign, not the underlying direction of the group difference.

These estimates also differ in adjustment. The recalculation is an unadjusted comparison based on the posted summaries. ANCOVA is a method for comparing group outcomes while accounting for covariates in a statistical model. The registry record identifies the method and the adjusted estimate, but the covariates and model details are not reported in the registry record. The adjusted and unadjusted estimates should therefore be described according to their respective methods rather than treated as identical calculations.

How should the p-value be read?

A p-value describes how compatible the observed data are with a statistical null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary registry analysis reports p < 0.001; the unadjusted recalculation also reports p < 0.001. These results indicate strong statistical evidence against a zero between-group contrast under the respective analyses and assumptions. They do not establish that every participant experienced a benefit or that the result applies to populations not represented by the trial.

The registry also reports 95% confidence intervals for the adjusted comparison, and the recalculation gives a 95% confidence interval for its unadjusted contrast. A confidence interval conveys uncertainty about the estimated contrast under the statistical method used. Its endpoints describe values compatible with the data and model at the stated confidence level; they are not a range containing a specified proportion of individual participant outcomes.

Why use an average over repeated readings?

Daily PEF measurements can vary. Averaging measurements over the treatment period is a way to characterize the overall measured response rather than putting all emphasis on an isolated reading. The record says that the endpoint was based on daily morning pre-dose recordings, with baseline measured during the run-in period. The analysis population required at least one available post-baseline efficacy evaluation. The registry record does not report the detailed missing-data method or how incomplete daily records contributed to each participant’s average.

Repeated observations can raise questions about within-participant correlation, measurement quality and missing readings. The registry describes use of an electronic device and specified procedures for collecting PEF, but the statistical handling of repeated daily values beyond the endpoint definition is not reported in the registry record. No further model assumptions should be inferred from the endpoint description alone.

What do the other analysis measures add?

The ACQ score is a continuous outcome, so its group changes and mean contrast describe averages on a score scale. The asthma-exacerbation outcome is a participant count, so it describes how many participants had an exacerbation during the stated treatment period. These outcomes have different scales and interpretations from PEF. A mean difference for a continuous measure should not be interpreted as a difference in event counts, and an event comparison should not be read as a change in lung function.

For event outcomes, estimates can be uncertain when event counts are limited. General statistical principle: fewer observed events usually leave less information for distinguishing plausible differences between groups, and a confidence interval can communicate that uncertainty. The exacerbation comparison has a reported recalculated risk-difference interval that includes zero, so it does not establish a clear between-group difference on that outcome. The registry record does not report a sponsor analysis for this endpoint.

What does over-dispersion mean in general?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It matters because a model that underestimates variability can produce uncertainty estimates that are too narrow and tests that are too optimistic. The registry record does not report an over-dispersion assessment for these outcomes, so no conclusion about whether it occurred in this trial can be drawn.

11. Confidence Intervals and Precision

The unadjusted recalculation for the primary endpoint estimates a BDP-minus-CHF mean difference of -20.08 L/min, with a 95% confidence interval from -28.2 to -11.96. The interval lies below zero, matching the negative direction of the contrast as expressed. Reversing the group order would reverse the signs; it would not change the underlying comparison.

The registry-reported adjusted estimate is 18.53 L/min, with a 95% confidence interval from 10.33 to 26.73. This interval lies above zero and is consistent with the adjusted comparison expressed in the CHF 1535 versus BDP direction. The reported p-value is p < 0.001. The adjusted result and the recalculation have different contrast orientations and adjustment, so their interval endpoints should not be compared as if they came from the same analysis.

In general, a confidence interval communicates uncertainty about an estimated group contrast under the analysis assumptions. A narrower interval indicates greater precision than a wider one on the same scale and for the same estimand. An interval that excludes zero is evidence of a nonzero contrast under the stated method, but it does not determine whether the difference is clinically important. The registry record does not report a clinical-importance threshold for PEF.

The posted standard deviations describe variation among participant measurements, not the precision of the treatment contrast. Precision also depends on the analysis population and the method used to estimate uncertainty. The registry record does not report all model details or the handling of missing repeated readings, so those aspects cannot be independently assessed from the posted summary alone.

12. 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 based on the observed effect, not the original trial design. They assume a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. Each planning scenario uses the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

These entries are participants per arm, not total event counts. For the primary continuous outcome, the rows illustrate planning for 100%, 75% or 50% of the observed effect. The columns for 80% and 90% power give the number of participants per arm estimated to be needed under the stated assumptions to detect that effect at the corresponding power level. Power is the probability, under the planning assumptions and a specified effect, that a statistical test would reject its null hypothesis.

The 90% power column requires more participants per arm than the 80% column for each stated effect scenario. Planning for a smaller effect also requires more participants per arm than planning for a larger effect. This is because smaller group differences are harder to distinguish from random variation without more information. The illustrations are not observed power and do not describe a post-trial probability that the study result is correct.

The sample-size illustrations should be read as conditional planning scenarios rather than recommendations. They use the observed effect as their starting point, and the effect anticipated for a future study could differ. The registry record does not report the assumptions used when the trial was originally designed.

13. 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 = -20.080; pooled standard deviation σ = 39.433.
2. n = 2 × (1.96 + 0.842)² × 39.433² / -20.080² = 60.5, rounded up to 61 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 <- -20.08                      # observed difference in means
sigma <- 39.4328919848103                     # 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(1577082)
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 = 61 (80% power), 82 (90% power)
 75% of observed effect: n per arm = 108 (80% power), 145 (90% power)
 50% of observed effect: n per arm = 243 (80% power), 325 (90% power)
power.t.test: 61.5 
Simulated power at n = 61 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry-reported primary analysis is an ANCOVA adjusted mean difference of 18.53 L/min, with a 95% confidence interval from 10.33 to 26.73 and p < 0.001. This is the sponsor-reported analysis recorded for the primary comparison. The registry record identifies the method but does not report the covariates included in the model.

The recalculation is a simple unadjusted comparison of the posted group means and standard deviations. It reports -20.08 L/min for BDP relative to CHF 1535, with a 95% confidence interval from -28.2 to -11.96 and p < 0.001. Its sign differs because the groups are ordered in the opposite direction from the registry-reported adjusted contrast. The estimates also differ because one is unadjusted and the other is adjusted.

There is no flagged discrepancy between these analyses in the registry record. Their numerical values should not be expected to match exactly, but their directions are consistent after accounting for the contrast ordering. The sponsor analysis answers the trial’s reported adjusted comparison; the recalculation offers a transparent, unadjusted check based on the posted summaries. Neither result removes the need to consider the endpoint’s clinical meaning, missing-data handling or the limits of the registry’s reported model details.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 15 outcome measures and 78 analyses. Examining multiple outcomes or analyses creates a multiplicity issue: even when there is no true difference for any outcome, repeated testing can increase the chance of at least one apparently positive result. General statistical principle: a prespecified primary outcome helps focus the main confirmatory question, while secondary findings are usually interpreted with regard to the number of comparisons and any adjustment strategy.

The record identifies the primary outcome and reports its ANCOVA analysis. It does not report a multiplicity adjustment, a testing hierarchy for secondary outcomes or whether the secondary analyses were intended as confirmatory or exploratory. Therefore, the strength of isolated secondary p-values cannot be assessed in the context of an unreported multiplicity plan. The primary result remains the clearest reported test of the stated trial objective, but the registry record alone does not establish how the full family of analyses was controlled.

The primary intent-to-treat population included randomized participants who received at least one administration of study drug and had at least one available post-baseline efficacy evaluation. This definition is not identical to including every randomized participant regardless of post-baseline data availability. The record gives the maximum numbers analyzed for primary efficacy but does not report the detailed reasons for exclusions or missing observations.

The registry record does not report the missing-data method, assumptions about missing outcomes, sensitivity analyses, or how incomplete daily PEF records were handled. Those details matter because results can depend on whether missingness is related to participants’ outcomes or treatment experience. No claim about the robustness of the primary estimate to missing data can be made from the reported information alone.

The safety population is described separately through the adverse-event denominators. The record does not provide a complete account of how participants moved between randomized, efficacy and safety populations. These reporting gaps limit assessment of the analysis process, but they do not change the values that the registry reports for the primary comparison.

16. 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 0.0% reporting threshold.

Most frequent non-serious adverse event terms

The safety results list 189 participants at risk in the CHF 1535 safety group and 180 in the BDP safety group. The recorded count of participants affected by serious adverse events is 0 in each group. Deaths are also recorded as 0 in each group, and no top serious-event terms are listed.

These are counts within the safety populations, not estimates of comparative risk with a confidence interval. A recorded count of zero means that no serious adverse events were listed for those groups in this registry record; it does not prove that the risk is absent. The record also lists 29 participants with other adverse events in the CHF 1535 group and 30 in the BDP group. Those counts concern other adverse events and should not be conflated with the serious-event figures.

The registry record does not give detailed event descriptions for the other adverse events in the information summarized for this analysis. The reported counts alone do not establish whether a treatment is safe or unsafe, and they do not support conclusions about rare or longer-term events. The safety findings should be read within the recorded safety populations and the 12-week treatment period.

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

The primary comparison shows a statistically clear difference between groups in change from baseline in average pre-dose morning PEF over the 12-week treatment period. The group means and the reported adjusted analysis point in the direction of a higher average change for CHF 1535 than for BDP, once the different contrast orderings are taken into account. The registry-reported adjusted interval excludes zero, as does the unadjusted recalculation when interpreted in its own direction.

This result concerns a measured lung-function endpoint among the analyzed adult participants. It does not show that every participant had an improvement, nor does it establish the size of a benefit for an individual. It also does not establish whether the observed difference crosses a threshold that patients or clinicians would consider important; such a threshold is not reported in the registry record.

The primary finding is not a complete account of treatment effects across symptoms, exacerbations, rescue medication or safety. The secondary outcomes address some of those domains, but the registry record does not report a multiplicity strategy, and numerical results are not available for every listed secondary measure in the information summarized. Their evidence should therefore be considered separately and with appropriate caution.

The comparison is limited to the trial’s population, interventions and treatment period. The registry describes adults whose asthma was not adequately controlled on specified inhaled corticosteroid regimens. It does not establish how the findings apply to people outside that population or to other treatment settings. The record’s short treatment period also does not answer questions about longer-term outcomes.

In short, the posted primary analysis supports a between-group difference in the specified PEF measure under the reported analysis. It does not, on its own, establish a comprehensive clinical advantage, long-term effects or the absence of important safety risks.

18. Why This Trial Matters Statistically

This trial illustrates why the estimand and the direction of a contrast matter when reading results. The recalculated mean difference is expressed as BDP relative to CHF 1535, while the registry-reported adjusted comparison is expressed in the opposite group order. Their signs therefore differ even though the direction of the group comparison is consistent. Reading a sign without checking which group is subtracted from which can reverse the apparent interpretation.

It also illustrates the distinction between an unadjusted re-calculation and a reported adjusted analysis. The posted group means allow a simple comparison, but ANCOVA reports an adjusted contrast. The values are not interchangeable, and the registry does not provide the model covariates needed to reproduce the adjusted analysis fully.

The primary endpoint is based on repeated daily measurements averaged over the treatment period. That design captures more than a single reading, while also making measurement procedures and missing-record handling relevant to interpretation. The registry describes the measurement procedure but does not report the full statistical handling of incomplete daily records.

Finally, the primary result and secondary outcomes answer different questions. A clear difference in PEF should not be assumed to imply a corresponding difference in symptoms, exacerbations or every other outcome. Considering the confidence interval, the adjustment status, the outcome definition and the unreported multiplicity and missing-data details gives a more complete statistical reading than relying on a p-value alone.

19. 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 primary endpoint is a physiological lung-function measure. While the registry describes PEF as an indicator of lung function, it does not report a threshold for interpreting the clinical importance of the observed between-group difference. The primary estimate therefore establishes a statistical contrast on the recorded scale, not its importance to patients.

The analysis population required at least one post-baseline efficacy evaluation. The registry record does not report detailed participant flow, reasons for missing observations, the method used to handle missing data or sensitivity analyses. It is not possible from the record to assess how alternative missing-data assumptions might affect the result.

The ANCOVA result is reported as adjusted, but the covariates and full model specification are not reported in the registry record. The unadjusted recalculation is consequently a useful check on the posted summaries, but it cannot reproduce the adjusted analysis. The two estimates also use opposite contrast orientations.

The trial lasted 12 weeks, so the reported results do not address longer-term outcomes. The study population was adults with asthma not adequately controlled on specified inhaled corticosteroid regimens; generalization beyond that population is not established by this record.

The registry lists many analyses and secondary measures, but the multiplicity approach is not reported. Numerical results are also not available for every listed secondary outcome in the summarized results. The record does not report the original sample-size justification, detailed repeated-measure modeling or complete safety-event descriptions for other adverse events. These limitations constrain how fully the results can be independently evaluated.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients — NCT01577082.
• Registry record last updated 2026-03-19; status last verified 2026-02.
• Results first posted 2026-03-19.
• 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.

23. Record Summary

NCT01577082 is a completed phase 3 randomized, quadruple-masked, parallel-group study sponsored by Chiesi Farmaceutici S.p.A. It compared CHF 1535 200/6µg pMDI with beclomethasone dipropionate HFA pMDI in adults with asthma not adequately controlled on specified inhaled corticosteroid regimens. The treatment period was 12 weeks, and the record lists enrollment of 542.

The primary endpoint was change from baseline in average pre-dose morning PEF over the treatment period. The registry-reported ANCOVA analysis gave an adjusted mean difference of 18.53 L/min (95% CI 10.33 to 26.73; p < 0.001). The unadjusted recalculation is expressed in the reverse group order and is consistent in direction.

The registry also lists secondary outcomes and safety counts. Details of multiplicity control, missing-data handling, the original sample-size justification and the adjusted model covariates are not reported in the registry record.