Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients (NCT02927366), a randomized phase 2 study. The primary outcome is Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 (Day 111).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, placebo-controlled, subject- and investigator-blinded phase 2 study of QCC374 in PAH. The registry lists Novartis Pharmaceuticals as the sponsor. Enrollment was 8. The study started on 2017-09-19, had a primary completion date of 2018-06-07, and is listed as terminated.

The brief description characterizes the study as non-confirmatory and says it was planned in two parts. Part 1 was an initial safety cohort with a 0.03 mg twice-daily starting dose. Part 2 was intended as a larger cohort with a 0.06 mg twice-daily starting dose, but it was not completed following early termination after Part 1. The registry does not report why the study was terminated.

Each planned part included screening for up to 28 days, a titration period of 2 weeks, a stable-dose period of 14 weeks, and safety follow-up for 28 days. The primary assessment was change from baseline in PVR at Week 16 (Day 111). Participants who were eligible at the end of the 16-week treatment period could choose to enter a separate long-term extension study; participation in that extension is not reported in the registry record.

The listed secondary outcomes include change from baseline over time in six-minute walk distance and, at Week 16 (Day 111), cardiac output, cardiac index, pulmonary capillary wedge pressure, systemic vascular resistance, and several right-ventricular echocardiographic measures. The registry lists 14 outcome measures but does not report analysis results for these 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.

Before assignment: Part 1 consisted of 8 subjects, randomized in a 6:2 ratio to QCC374 or placebo. The planned bid dose levels in Part 1 were 0.03 mg, 0.06 mg and 0.12 mg. Subjects began dosing at 0.03 mg bid.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 (Day 111), measured over Baseline, Week 16 (Day 111).

The primary endpoint was change from baseline in pulmonary vascular resistance (PVR) at Week 16 (Day 111), measured in dyn*s/cm5. PVR describes the resistance to blood flow through the pulmonary circulation. The registry states that PVR is derived from cardiac output and can be calculated using mean arterial pressure and mean pulmonary artery wedge pressure. Those inputs make PVR a measure that brings pressure and flow information together.

In general, a change-from-baseline endpoint compares a participant’s measurement at follow-up with their starting measurement. The registry specifies that a higher negative number in PVR indicates improvement. That direction matters when interpreting any reported change: the sign of a change is meaningful only in relation to the endpoint’s stated direction.

PVR is used in this study as an efficacy measure in PAH, alongside the listed measures of exercise capacity, cardiac function, and vascular pressures. The primary outcome description says that only descriptive analysis was performed. However, the registry record does not report group means, standard deviations, changes from baseline, or a numerical comparison at Week 16. Thus, the endpoint’s definition and intended assessment are described, but its observed result and precision cannot be evaluated from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study used randomized allocation, a parallel-group design, placebo matching, and subject and investigator blinding. In general, randomization is intended to make treatment assignment independent of participant characteristics, while blinding is intended to reduce the influence of treatment knowledge on care, measurement, and reporting. These design features do not, by themselves, guarantee that the resulting groups are comparable in a small study or that results are precise. The registry record does not report details of the randomization procedure or how blinding was maintained.

What does a change from baseline represent?

In general, a change-from-baseline measure is calculated by comparing a follow-up value with a participant’s baseline value. The primary outcome applies that concept to PVR at Week 16 (Day 111). The registry defines the direction of improvement as a higher negative number. To interpret a reported change, the baseline and follow-up definition, sign convention, and units all need to be clear. The record supplies the endpoint definition and unit but does not report the observed baseline or follow-up summaries.

What does a mean and standard deviation describe?

The primary outcome is identified as a mean of a continuous measure, with standard deviation as the dispersion measure. In general, the mean describes the average observed value, while the standard deviation describes the spread of individual values around that average. A standard deviation is not the same as a confidence interval: it describes variability in the measurements, whereas a confidence interval expresses uncertainty about an estimated quantity. The registry record does not report the mean or standard deviation for the primary outcome, nor does it report a confidence interval.

Why does a confidence interval matter?

In general, a confidence interval gives a range of values compatible with the data and the statistical method used. Its width conveys precision: wider intervals indicate less precise estimation. A confidence interval would help readers assess the range of plausible treatment differences, but none for the primary outcome is reported in the registry record. Without the numerical estimates and their uncertainty, the record does not support a quantitative account of the comparative effect.

What is the role of descriptive analysis?

The primary outcome description explicitly says only descriptive analysis was performed. In general, descriptive analyses summarize the measurements observed in the study without necessarily carrying out a formal hypothesis test or estimating a treatment contrast. The registry record reports zero analyses, and does not give a primary-outcome estimate or a formal comparison. A numerical p-value, adjusted or otherwise, is not reported in the registry record. Consequently, statistical significance cannot be evaluated from these results.

How should planning calculations be understood?

In general, sample-size calculations use assumptions about the effect to detect, variability, significance level, allocation, and statistical method to illustrate how many participants might be needed under those assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects specified as fractions of an observed effect. Such calculations are planning illustrations, not observed evidence and not a substitute for trial results. The record does not report that these were the study’s original design assumptions or provide a sample-size justification. No planning counts are reported in the registry record. The calculations should not be interpreted as observed power.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a model assumes. When a statistical method assumes less variability than is present, its uncertainty estimates can be too small and its inferences too confident. This general issue is most directly relevant to models for counts or rates. The primary endpoint is continuous, and the registry record does not report a model-based primary analysis or an over-dispersion assessment. It is therefore not possible to say that over-dispersion affected this study’s primary analysis.

The registry does not report a detailed statistical analysis plan, interim analyses, methods for handling missing data, or a rationale for the planned sample size. These aspects should not be inferred from the study’s design labels or from the fact that it was terminated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple secondary outcomes. When several outcomes, time points, or comparisons are examined, the chance of obtaining at least one apparently notable result can increase. In general, a prespecified multiplicity strategy may control that issue, but the registry record does not report one. It also does not report a detailed statistical analysis plan or identify a hierarchy among the secondary outcomes. The primary outcome description says only descriptive analysis was performed.

The primary outcome is specified at Week 16 (Day 111), while one secondary outcome—change from baseline in six-minute walk distance—is described over time. Several other secondary outcomes are specified at Week 16 (Day 111). The record lists 14 outcome measures, but it does not provide analysis results for them. The primary outcome was not reduced to a single comparison in the posted results because it has several categories or time points.

The record defines the Pharmacodynamic analysis set as randomized participants who received at least one dose and had at least one evaluable pharmacodynamic assessment, with data available for analysis. It does not report how many participants were included in that set or how many had evaluable PVR measurements at the primary time point. The number and pattern of missing primary-endpoint observations, reasons for missingness, and any method used to address missing data are not reported in the registry record.

These omissions prevent assessment of how the analysis population was formed, whether missing observations could have affected the descriptive summaries, and how multiplicity was handled. They also make it difficult to distinguish an absence of evidence from evidence of no difference.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: syncope (16.7%).

The registry lists serious adverse events separately from other adverse events. In the QCC374 group, 6 participants were at risk for serious adverse events, and 1 was listed as affected; in the placebo group, 2 were at risk, and none was listed as affected. For other adverse events, the record lists 6 at risk and 6 affected in the QCC374 group, and 2 at risk and 1 affected in the placebo group. No deaths are listed in either group.

Syncope is the leading serious adverse-event term listed, at 16.7%. The registry record does not give further detail about its treatment-group allocation or clinical course. These counts describe events recorded in this study; they do not establish that treatment caused an event or that a difference between groups is reliable. In general, event rates based on small groups are imprecise, and a zero count does not show that an event cannot occur. The registry does not report an inferential comparison of adverse events.

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

The record establishes that QCC374 was studied against matching placebo in a randomized, blinded, parallel-group phase 2 study of adults with PAH. It also defines PVR change at Week 16 (Day 111) as the primary efficacy outcome and states the direction in which a more negative change indicates improvement. These details clarify what the study intended to assess.

The registry record does not report numerical PVR results, a treatment-group contrast, or a confidence interval. Therefore, it does not show the size or precision of any difference in PVR between QCC374 and placebo. It also does not establish whether any observed difference would be attributable to treatment. A missing numerical result should not be interpreted as a null result.

The record reports selected adverse-event counts, including serious adverse events and deaths, but these are descriptive observations in groups with few participants. They cannot provide a precise estimate of comparative safety. The record does not report enough detail to assess the timing, duration, severity, or treatment relatedness of the listed events.

The study was terminated after Part 1, and the planned Part 2 was not completed. The reason for termination is not reported in the registry record. The incomplete study and absent primary-outcome summaries limit the conclusions that can be drawn about the intended efficacy question. No claim about clinical benefit or lack of benefit follows from these registry data alone.

In general, a study’s design describes how evidence was intended to be collected, while its results determine what can be estimated from the observations. Here, the design and endpoint are described, but key primary-outcome findings and analysis details are not reported. The most defensible interpretation is therefore limited to the study conduct and the adverse-event counts recorded, without a quantitative efficacy conclusion.

13. Why This Trial Matters Statistically

This study illustrates why design details and outcome reporting need to be read together. Randomization, placebo control, and blinding describe safeguards intended to support a fair comparison. But interpretation also depends on knowing how many participants contributed evaluable outcomes, what the observed measurements were, and how uncertain the estimates are. The registry record does not report those primary-outcome results.

The early termination and incomplete Part 2 are important context. The study was planned with an initial safety cohort followed by a larger cohort, but only Part 1 was completed. That means the record does not document the larger planned stage of the investigation. The reason for termination is not reported, so the reason should not be inferred.

Statistically, the record also shows the distinction between a planned endpoint and an estimable treatment effect. A well-defined PVR endpoint identifies what was to be measured, but without group summaries and a treatment contrast, the magnitude and precision of the comparison remain unknown. Descriptive analysis is not a substitute for reporting those values.

The safety counts likewise demonstrate why denominators and event counts matter. The groups at risk were small, and the registry gives event counts rather than a formal comparison. These observations are useful as a record of what was reported, but they cannot support precise conclusions about comparative safety.

For clinical researchers and biostatisticians, the study underscores the value of complete reporting of analysis populations, outcome summaries, uncertainty, missing-data handling, and analysis plans. Such information allows readers to distinguish an inconclusive or incomplete record from evidence of no effect.

14. Limitations

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

Several limitations are specific to the information recorded for this study. Enrollment was 8, and the study was terminated after Part 1; the planned Part 2 was not completed. The reason for termination is not reported in the registry record. The registry does not report the number of participants who contributed evaluable PVR data at Week 16 (Day 111), so the size of the primary analysis population cannot be established from the outcome record.

No primary-outcome means, standard deviations, changes from baseline, treatment contrast, confidence interval, or p-value are reported. Although the primary endpoint description states that only descriptive analysis was performed, the underlying descriptive results are not reported. The record also does not provide outcome results for the listed secondary measures.

The registry does not report a detailed statistical analysis plan, sample-size justification, interim analysis details, or missing-data methods. It does not report how many primary-endpoint measurements were missing, why they were missing, or whether the analysis population differed from the randomized population. These gaps prevent assessment of potential bias from missing observations and of the prespecification of analyses.

Safety information is also limited to the listed counts and serious-event term. Additional details about event timing, severity, duration, and relationship to study treatment are not reported in the registry record. Given the small groups, the counts do not provide precise comparative estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients — NCT02927366.
• Registry record last updated 2021-01-05; status last verified 2020-02.
• Results first posted 2019-08-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This phase 2 study randomized adults with PAH to QCC374 or matching placebo in a parallel-group, subject- and investigator-blinded design. Enrollment was 8. The study was terminated after Part 1, and the planned Part 2 was not completed.

The primary outcome was change from baseline in PVR at Week 16 (Day 111), with descriptive analysis specified. The registry record does not report numerical primary-outcome results or a treatment comparison. It lists serious adverse events affecting 1 participant in the QCC374 group and none in the placebo group, with no deaths listed. These observations are descriptive and do not establish comparative efficacy or safety.