EMPIRE CF: A Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of CTX-4430 in Adult Cystic Fibrosis (CF) Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EMPIRE CF: A Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of CTX-4430 in Adult Cystic Fibrosis (CF) Patients (NCT02443688), a randomized phase 2 study. The primary outcome is Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1).

2. Clinical Question

The central statistical question is whether the observed difference between the pooled active-treatment group and placebo is sufficiently precise to distinguish a treatment-group difference from uncertainty in the trial estimate. The posted primary comparison is a mean difference of 0.16, with a 95% confidence interval from -2.20 to 2.50 and p = 0.45. That interval includes zero, so the posted analysis does not provide clear statistical evidence of a difference on this endpoint. It also spans values on both sides of zero, leaving uncertainty about the direction and size of any difference.

The trial also assessed pulmonary exacerbations and other measures, but these outcomes are secondary to the primary ppFEV1 question. Their results can add context, yet they do not replace the primary comparison or establish a separate confirmatory conclusion. The registry record does not report a multiplicity plan that would clarify how to interpret a collection of secondary tests.

3. Trial Design

EMPIRE CF was a randomized, parallel-group, placebo-controlled phase 2 study sponsored by Celtaxsys, Inc. The registry lists triple masking, while the brief summary describes the study as double-blind. It does not specify which parties were masked, so the masking roles are not reported in the registry record. The listed enrollment was 200, and the study status is completed.

Participants were assigned to 100 mg CTX-4430, 50 mg CTX-4430, or matching placebo. Each regimen was an oral capsule taken once daily for 48 weeks. For the primary analysis, the registry states that the 50 mg and 100 mg groups were pooled and compared with placebo. The primary analysis population is described as all subjects randomized to and receiving at least 1 dose of assigned treatment; this is a treated randomized population rather than an explicitly stated intention-to-treat population including everyone randomized.

The primary endpoint was the difference from placebo in absolute change from baseline in ppFEV1, assessed at Week 48. The registry also lists pulmonary exacerbation outcomes, changes in other lung-function measures, biomarkers, and C-reactive protein among secondary outcomes. The available record does not provide a complete description of the study protocol, allocation procedures, dose-pooling rationale, or detailed statistical analysis plan. Those details are not reported in the registry record and cannot be inferred from the posted outcome summaries.

The arm summaries list 66 participants in the 100 mg group, 67 in the 50 mg group, 133 in the pooled group, and 66 in the placebo group for the primary outcome. Those are the reported outcome-group counts, not a replacement for the registry’s stated overall enrollment. The record does not explain any difference between enrollment and the counts contributing to particular outcomes.

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: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. The primary analysis was based upon the pooled results of the 100mg and 50mg doses.

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: One subject in the matching placebo cohort was randomized but did not take any study drug. Therefore, the matching placebo group has 66 subjects listed instead of 67 subjects making it a total of 199 subjects who received study drug.

6. Primary Endpoint

The registry lists the primary outcome as Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1), measured over Baseline, Week 48.

ppFEV1 expresses forced expiratory volume in 1 second relative to a predicted value. The primary endpoint is the absolute change in that measure from baseline to Week 48, compared between the pooled CTX-4430 groups and placebo. An absolute change is expressed in the endpoint’s units, rather than as a relative percent change from baseline.

FEV1 is a measure of airflow during a breathing test. Expressing it as a percent of a predicted value places an individual measurement in relation to a reference value. In a clinical trial, comparing change from baseline can account for the starting measurement when describing how the groups’ measurements shifted over follow-up. The registry identifies baseline and Week 48 as the measurement times, but the detailed rules for handling measurements not collected at Week 48 are not reported in the registry record.

The group mean change describes the average observed change in each group; the comparison between groups addresses whether the average change differed. The posted pooled CTX-4430 mean change was -2.53, with a 95% confidence interval from -3.88 to -1.18. The placebo mean change was -2.69, with a 95% confidence interval from -4.63 to -0.75. These within-group summaries are not themselves the randomized comparison. The inferential comparison is reported separately as a mean difference of 0.16, with a 95% confidence interval from -2.20 to 2.50.

Using a prespecified primary endpoint helps focus interpretation on the principal trial question. It does not, by itself, show that a particular difference is clinically important. A clinically meaningful threshold for ppFEV1 is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the confidence interval communicate?

General statistical explanation: a confidence interval describes the uncertainty around an estimate under the analysis model and its assumptions. A narrower interval indicates greater precision than a wider interval. For a difference in means, zero represents no difference between groups. An interval that includes zero is compatible with no difference and with values on either side of zero. The primary 95% confidence interval runs from -2.20 to 2.50, so the estimated difference is uncertain in both direction and magnitude.

A confidence interval is not a guarantee that the true effect lies inside its bounds, and it is not a direct statement about clinical importance. Clinical interpretation requires context, including a meaningful-difference threshold; such a threshold is not reported in the registry record. A p-value addresses compatibility between the data and a specified null model, conditional on assumptions. It does not express the probability that the null hypothesis is true, and a p-value above a conventional threshold does not demonstrate equivalence.

Why distinguish group changes from the between-group contrast?

The mean change in each arm is a descriptive summary of that arm. The primary question compares the arms. Separate confidence intervals for arm means are not the same as a confidence interval for their difference, and their overlap is not a formal test of that difference. The registry reports an ANOVA analysis for the pooled primary comparison, with a mean difference in final values of 0.16, a 95% confidence interval from -2.20 to 2.50, and p = 0.45. The record does not give sufficient detail to reconstruct the full model specification or identify covariates used.

The reported endpoint summaries describe absolute change from baseline. The sponsor analysis is labelled as a mean difference in final values. The registry does not explain the exact relationship between that analysis parameter and the change-score descriptions or provide enough model detail to treat the two as independently interchangeable calculations. For inferential interpretation, the posted sponsor analysis is the relevant reported comparison.

How should the exacerbation rates be read?

General statistical explanation: event rates account for the amount of observation time, rather than simply counting whether each person had an event. A rate ratio compares the event rates in two groups; a value of one represents equal rates under that measure. The 95% intervals for the posted rate-ratio recalculations include one for both dose comparisons. Their unadjusted p-values are 0.972 for 100 mg and 0.719 for 50 mg. These are recalculations from posted summary statistics, not the registry’s reported inferential analyses.

The recalculation is marked as Poisson-based. General explanation: a Poisson model is one approach to counts of events over time, with an assumption that the event-count variability is consistent with the modeled rate. Recurrent events among the same participants can be correlated, and event counts can vary more than a simple Poisson model allows. Such over-dispersion can make a simple model’s uncertainty estimates too small if it is not addressed. The registry does not report a detailed model for the sponsor’s exacerbation-rate estimates, nor does it report checks for over-dispersion or dependence among recurrent events. The recalculation should therefore be read as a simple, unadjusted illustration rather than a substitute for a prespecified analysis.

What do the binary outcome comparisons represent?

For participants without a pulmonary exacerbation while in the study, the posted recalculation uses a risk difference: the difference between the proportions in the two groups. A risk difference of zero represents equal proportions. The recalculated intervals for both doses include zero, and the unadjusted p-values are 0.359 and 0.303. These comparisons use the reported counts and group sizes and do not account for any adjustment or multiplicity that may have been part of a fuller analysis. The registry does not post sponsor inferential analyses for this outcome.

How should planning illustrations be understood?

General statistical explanation: sample-size planning asks how many participants might be needed to detect a specified effect under stated assumptions. The registry’s planning illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and fractions of the observed effect. They are not the trial’s original sample-size justification, because that justification is not reported in the registry record. They are also not observed power and cannot tell whether the study was adequately designed for its original question.

Planning values can change sharply when the assumed effect is made smaller, because a smaller difference is harder to distinguish from random variation. That is why the illustrations show planning for 100%, 75%, and 50% of the observed effect. They are hypothetical planning scenarios, not estimates of how many participants were needed after the study was completed. For the event-rate outcomes, the recalculation also depends on rate and follow-up assumptions; the registry describes the event planning output as a total number of events, while other planning outputs are participants per arm.

10. Analyses Reported by the Sponsor

The registry’s sponsor-reported primary analysis is an ANOVA comparison of pooled CTX-4430 with placebo. It reports a mean difference in final values of 0.16, a 95% confidence interval from -2.20 to 2.50, and p = 0.45. The interval includes zero, and the result does not show a statistically clear difference in the primary comparison. The registry record does not report enough detail about the ANOVA specification to reconstruct it fully.

The posted arm summaries give mean absolute changes from baseline, whereas the sponsor analysis is described as a mean difference in final values. Those descriptions are not identical, and the record does not provide the details needed to determine exactly how the analysis relates to the displayed change summaries. The sponsor’s inferential result should therefore be interpreted on its own terms rather than replaced by an independently constructed contrast.

There is no flagged discrepancy between the posted analysis and the recalculation status. The exacerbation-rate and no-exacerbation comparisons described as recalculated are simple unadjusted analyses of summary data; they do not reproduce a detailed sponsor model. For the primary endpoint, the sponsor’s own reported inferential analysis is the principal result available in the registry. Neither its p-value nor its confidence interval establishes equivalence or the absence of a potentially important difference.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, but it does not report a multiplicity plan. In particular, it does not describe a hierarchy of hypotheses, a family of tests, or an adjustment to control the chance of false-positive findings across multiple comparisons. Without those details, secondary p-values should be interpreted cautiously. An unadjusted p-value answers a single-test question under its assumptions; it does not account for the broader set of outcomes being examined.

The registry record also does not report whether interim analyses were planned or conducted, whether the analysis plan was finalized before unblinding, or how missing outcome measurements were handled. These omissions matter because repeated looks at accumulating data and outcome-dependent missingness can affect uncertainty and interpretation. The fact that the primary analysis population includes randomized participants who received at least 1 dose does not explain how participants with missing Week 48 measurements entered the analysis.

The record identifies the primary population as the Full Analysis Population and describes it as all subjects randomized to and receiving at least 1 dose of assigned treatment. It does not report the detailed analysis population for every secondary endpoint, the number with observed measurements at each time point, or imputation and sensitivity-analysis procedures. The registry record does not report a protocol-level sample-size justification, an assumed target effect, or the planned power for the primary endpoint. The sample-size illustrations based on observed effects are separate planning exercises and cannot fill those gaps.

These missing details do not invalidate the posted estimates, but they limit how completely the analysis can be evaluated. The confidence interval and p-value summarize the reported primary comparison; they do not reveal the impact of missing data, unreported model choices, or multiplicity procedures. Those aspects require a fuller protocol or statistical analysis plan, and are not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infective pulmonary exacerbation of cystic fibrosis (34.3%), haemoptysis (3.0%), antibiotic therapy (3.0%), haemolytic anaemia (1.5%), distal intestinal obstruction syndrome (1.5%).

The registry reports serious adverse event counts for each treatment group. Serious events affected 27 participants in the 100 mg CTX-4430 group, 26 in the 50 mg group, and 21 in the matching placebo group. The corresponding groups at risk were 66, 67, and 66. The registry reports zero deaths in each group. These counts describe what was recorded in the study; they do not, by themselves, establish that treatment caused or prevented an event.

All participants in the two CTX-4430 groups and 65 participants in the placebo group are listed as affected by other, non-serious adverse events. Serious adverse events and other adverse events are separate categories in the registry, and these counts should not be combined into a single measure. The leading serious-event term listed is infective pulmonary exacerbation of cystic fibrosis at 34.3%; other listed terms include haemoptysis and antibiotic therapy at 3.0% each, and haemolytic anaemia, distal intestinal obstruction syndrome, and appendicitis at 1.5% each. The record does not provide enough detail to attribute those term percentages to a particular treatment group in this summary.

Comparing counts alone does not account for event duration, recurrence, severity beyond the registry category, or differences in follow-up. The registry’s safety figures are descriptive and should be read in that limited context.

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

The primary result estimates a difference in mean ppFEV1 change between pooled CTX-4430 and placebo at Week 48. The sponsor-reported mean difference is 0.16, with a 95% confidence interval from -2.20 to 2.50 and p = 0.45. The result does not show a statistically clear difference, but it also does not demonstrate that the groups are the same. The confidence interval permits a range of effects in either direction.

Failure to show a statistically clear difference is not proof of no effect. Evidence of equivalence would require a prespecified equivalence margin and an analysis designed to test whether the confidence interval falls within that margin. The registry does not report an equivalence or noninferiority objective or margin. Likewise, the p-value is not the probability that CTX-4430 has no effect, and it does not measure the clinical importance of the estimate.

The result applies to the study’s setting, participants, treatment regimens, and follow-up as recorded: adults with cystic fibrosis, daily oral treatment, and assessment through Week 48. The primary analysis pooled the 50 mg and 100 mg groups, so it does not establish separate conclusions for each dose. The registry record does not report subgroup analyses sufficient to describe whether results differed by participant characteristics.

The secondary outcomes and safety counts add descriptive context but do not provide a basis for a definitive overall benefit or harm conclusion. Several secondary comparisons are unadjusted, and multiplicity handling is not reported. The serious adverse event counts are not causal estimates. No clinical recommendation follows from these registry results alone; the data describe the estimates and uncertainty observed in this trial.

14. Why This Trial Matters Statistically

This trial is statistically informative because it makes the distinction between observed change and comparative evidence visible. The pooled CTX-4430 group and placebo both had negative mean changes in ppFEV1, but the scientific question is the between-group contrast. The sponsor analysis addresses that contrast directly, and its confidence interval shows why a single point estimate should not be read without its uncertainty.

The result also illustrates why a nonsignificant p-value does not settle a question. The reported p-value is 0.45, while the interval extends from -2.20 to 2.50. That combination indicates limited precision for distinguishing effects in either direction; it is not evidence that all potentially meaningful differences have been excluded. Without a clinically meaningful threshold or equivalence margin in the registry, the clinical implications of the interval cannot be determined from the posted result alone.

The secondary outcomes demonstrate another general issue in trial interpretation: multiple outcomes can be useful for understanding a study, but unadjusted findings do not necessarily carry the same evidential weight as a prespecified primary comparison. The registry does not report a multiplicity strategy, so the secondary results are best treated as contextual rather than definitive.

Finally, the record exposes the importance of transparent analysis details. The primary population is described, but missing-data procedures, interim analyses, multiplicity handling, and the detailed model specification are not reported. Those omissions constrain reproducibility and make it harder to assess the robustness of the estimates. Statistical interpretation depends not only on numerical results but also on knowing how the data were analyzed.

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 is a limited account of the trial’s statistical methods. It does not report the complete protocol or statistical analysis plan, including the planned sample-size justification, target effect, interim-analysis approach, multiplicity strategy, and missing-data procedures. It also does not give sufficient model detail to reconstruct the sponsor’s ANOVA analysis. These omissions restrict independent assessment of analytic choices and robustness.

The primary analysis pools the 50 mg and 100 mg doses. That is the stated primary approach, but the registry does not report the rationale for pooling or a formal primary comparison for each dose separately. The dose-specific mean changes are descriptive and should not be treated as a substitute for a planned dose comparison. The reported sponsor parameter is described as a mean difference in final values, while the endpoint is described as change from baseline; the record does not fully explain this distinction.

For the exacerbation outcomes, the posted comparative calculations are unadjusted recalculations from summary statistics. A simple Poisson-based rate analysis may not account for correlation between repeated events within a participant or over-dispersion. The registry does not report whether the sponsor’s method addressed these features. The event-rate recalculations should therefore not be regarded as a reproduction of an undocumented sponsor model.

The registry does not provide detailed information on the number of missing observations at each assessment, reasons for missingness, or sensitivity analyses. Nor does it report a clinically meaningful ppFEV1 threshold that would help interpret the range of values compatible with the primary confidence interval. These limitations do not change the numerical result, but they narrow what can be concluded from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: EMPIRE CF: A Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of CTX-4430 in Adult Cystic Fibrosis (CF) Patients — NCT02443688.
• Registry record last updated 2019-09-04; status last verified 2019-08.
• Results first posted 2019-07-25.
• 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

NCT02443688 is a completed phase 2 randomized, parallel-group study of once-daily oral CTX-4430 versus matching placebo in adults with cystic fibrosis. Treatment was planned for 48 weeks, and the primary endpoint was absolute change from baseline in ppFEV1 at Week 48. The primary analysis pooled the 50 mg and 100 mg groups.

The sponsor-reported primary comparison was a mean difference of 0.16, with a 95% confidence interval from -2.20 to 2.50 and p = 0.45. This does not show a statistically clear difference, while the interval leaves uncertainty about the direction and size of any difference. Secondary outcomes and adverse event counts provide context, but their interpretation is limited by unadjusted comparisons and missing details about multiplicity, missing data, and the full analysis plan.