Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension (NCT00540436), a non-randomized phase 2 study. The primary outcome is Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12.

2. Clinical Question

This question concerns change in a functional measure over time among participants in the study. Six-minute walk distance records how far a participant can walk during a six-minute test. The primary outcome is therefore an assessment of walking capacity, not a direct measurement of pulmonary artery pressure or another physiological mechanism.

The registry also identifies secondary questions about dyspnea, World Health Organization functional classification, clinical worsening, pulmonary and right atrial pressure, cardiac index, cardiac output, pulmonary vascular resistance, safety, tolerability, and pharmacokinetics. These outcomes broaden the study’s descriptive scope, but they do not create a control group. Without a randomized comparator, changes over time cannot by themselves distinguish a treatment-associated change from other influences on participants’ measurements.

The registry record does not report a numerical result for the primary outcome. It therefore does not permit a conclusion about the size, direction, or precision of the mean change from baseline to Week 12.

3. Trial Design

The registry identifies this as a Phase II study of GSK1325760A in pulmonary arterial hypertension. Its official title describes an open-label Phase II/III study, while the phase field lists Phase II. The record reports an enrollment of 25 and a completed status. The listed start was 2007-08 and the primary completion was 2009-01.

The design is single-group and non-randomized, with no masking. Participants received GSK1325760A in the sole study arm. There is no separate control arm described in the registry. Accordingly, the design can document outcomes among participants treated in the study, but it does not provide a randomized, like-for-like treatment comparison. Changes between baseline and follow-up are within-participant changes, not estimates of a difference between assigned groups.

The primary endpoint was mean change from baseline in six-minute walk distance at Week 12. The registry defines the change as the Week 12 value minus baseline and identifies the Full Analysis Set as the analysis population. The definition excludes registered participants who did not receive any investigational product and those without an efficacy assessment after administration. The record states that last observation carried forward was the imputation technique.

Secondary outcomes include mean changes in six-minute walk distance at Week 24 or withdrawal, Borg Dyspnea Index at Weeks 12 and 24, and several measures of cardiac function and pulmonary hemodynamics at Weeks 12 and 24. Other listed assessments concern functional classification and time to clinical worsening at Week 24. The registry also describes safety, tolerability, and steady-state plasma pharmacokinetics as secondary objectives.

The registry does not report the rationale for the enrollment target, a detailed statistical analysis plan, or a protocol-based sample-size justification. A rationale should not be inferred from the enrollment count or from any planning illustration based on an observed effect.

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.

First 12-Week Treatment Period

Reasons for not completing this period:

Second 12-Week Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): all participants registered, with the exception of those who had not received any dose of the investigational product and those who had no efficacy assessment after administration of the investigational product. Imputation technique was last observation carried forward.

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 Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 12, measured over Baseline and Week 12.

The primary endpoint is mean change from baseline in six-minute walk distance at Week 12, measured in meters. The test records the distance a participant can walk over six minutes. Change is defined as the Week 12 distance minus the baseline distance, so the endpoint describes the average within-participant change over that interval.

Walking distance is used as a functional measure of exercise capacity. It captures performance during a standardized activity and can be interpreted alongside other clinical assessments. It is not a direct measure of pulmonary artery pressure, cardiac function, or the underlying biological process of pulmonary arterial hypertension. Those domains appear separately among the listed secondary outcomes.

A mean summarizes the average change across the participants included in the analysis. The standard deviation describes how much individual changes vary around that mean; it is not the same as the uncertainty around the estimated mean. A confidence interval, when reported, would describe the precision of the estimated mean under the assumptions of its analysis. The registry record does not report a numerical mean change, standard deviation, or confidence interval for this primary endpoint.

The Full Analysis Set includes registered participants except those who received no dose or had no post-administration efficacy assessment. The record states that missing outcome values were handled using last observation carried forward. That method uses an earlier recorded value in place of a later missing value; its implications depend on why data are missing and whether the earlier value remains a reasonable representation of the later outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines the primary outcome as a mean change in a continuous measure. General statistical interpretation of this kind of endpoint involves distinguishing the estimated average change from the variation among participants and from the uncertainty in the estimate. The record specifies a standard deviation as the measure of dispersion, but does not report the primary outcome’s numerical estimate or dispersion.

What does a mean change represent?

For each participant with the necessary measurements, change is calculated by subtracting the baseline value from the Week 12 value. The study then describes the mean of those changes in the Full Analysis Set. A positive or negative value would indicate the direction of average change under that subtraction convention, but the registry record does not give the value. No direction or size should therefore be inferred.

The mean is useful for expressing the central tendency of participant changes, but it can conceal variation. Participants may have changes that differ substantially from the average. A standard deviation describes the spread of individual observations around the mean. It does not directly state how precisely the mean has been estimated. A confidence interval is a general way to express uncertainty around an estimate; its width depends on the amount of information and variability as well as the method used to calculate it. No confidence interval for the primary endpoint is reported in the registry record.

What does the analysis population mean?

The Full Analysis Set is defined as all registered participants except those who received no dose of the investigational product and those who had no efficacy assessment after administration. This definition makes receipt of treatment and availability of a post-administration assessment conditions for inclusion. The registry does not report the number of participants meeting the definition or the number contributing a Week 12 measurement.

The population used for an analysis matters because estimates apply to the participants included in that analysis. Excluding participants without post-dose assessment can affect the representativeness of the analyzed group if missing assessments are related to participants’ outcomes or circumstances. General statistical practice therefore considers how missingness arose, how many measurements are missing, and whether the analysis method relies on assumptions about those missing values. Those details are not reported in the registry record.

What is last observation carried forward?

The record states that last observation carried forward was used for imputation. In general, this approach substitutes a participant’s most recent observed measurement when a later value is missing. It can retain participants with incomplete follow-up in an analysis, but it assumes that the carried-forward observation is an appropriate substitute for the missing measurement. That assumption may not match the participant’s actual later outcome, particularly when the outcome could change over time.

Last observation carried forward does not remove uncertainty about missing data. Its impact depends on the timing and reasons for missing observations and on the pattern of subsequent outcomes that would have occurred. The registry record does not report the amount or pattern of missingness, the reasons measurements were missing, or sensitivity analyses evaluating alternative assumptions.

What can a single-group analysis estimate?

A single-group analysis can describe observed change over time in the included participants. It cannot make the same controlled comparison as a randomized study with a concurrent comparator. In general, a before-and-after change may reflect the intervention, the natural course of illness, other care, measurement variation, or other influences. Without a comparator, these explanations cannot be separated through the design alone.

Masking is also relevant to measurement and reporting. This study is listed as having no masking and as open-label. General statistical interpretation recognizes that knowledge of treatment status can influence expectations, participant responses, clinical assessments, or study procedures. The registry does not report additional measures intended to address such influences.

How should multiple outcomes be considered?

The registry lists 10 outcome measures and 2 analyses. In general, examining multiple outcomes creates multiple opportunities to observe apparently notable results by chance. Prespecified priorities, clear distinctions between primary and secondary outcomes, and appropriate multiplicity methods can help frame interpretation. The registry record does not report a multiplicity strategy, a complete statistical analysis plan, or whether the listed analyses were prespecified.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power, and are not evidence that the actual single-group study was designed with those assumptions. The record does not report the trial’s own sample-size justification. It also does not provide a numerical primary effect in the information from which to assess such a planning illustration.

Statistical methods are most interpretable when the estimate, uncertainty, analysis population, missing-data handling, and prespecified plan are all available. The registry supplies the endpoint definition and some analysis details, but does not report enough numerical results or planning information to evaluate the primary estimate or its inferential analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("GSK1325760A")
n   <- c(25)
m   <- c(33.49)
sp  <- c(43.236)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  GSK1325760A  25  33.490  43.236  15.643  51.337

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary six-minute walk distance endpoint and secondary assessments of symptoms, functional classification, clinical worsening, cardiac measures, pulmonary hemodynamics, safety, tolerability, and pharmacokinetics. It also reports 2 analyses. The registry record does not describe a prespecified hierarchy among outcomes, a statistical plan for multiplicity, or whether any adjustment for multiple testing was used.

As a general statistical matter, testing or interpreting many outcomes can make isolated findings harder to distinguish from chance patterns. A clear primary outcome helps focus interpretation, but secondary outcomes still require context about their planned role and analysis. No claim about multiplicity control can be made from the record.

For the primary endpoint, the registry defines the Full Analysis Set by excluding participants who received no dose and those without an efficacy assessment after administration. It states that last observation carried forward was used to impute missing values. The number of participants in this analysis population, the number with missing Week 12 data, and the reasons for missingness are not reported in the registry record.

In general, the consequences of imputation depend on how missingness occurred and on whether the assumptions of the method are plausible. Carrying an earlier value forward may not reflect a participant’s later outcome. The record does not report sensitivity analyses using alternative missing-data assumptions or enough information to assess the influence of imputation on the primary estimate.

The registry also does not report whether analysis populations or missing-data procedures differed for the secondary outcomes. Those details, like the results for the primary outcome, are not reported in the registry record.

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

The study addresses whether mean six-minute walk distance changed between baseline and Week 12 among participants included in the defined Full Analysis Set. The registry describes how that endpoint was measured and how missing values were handled. It does not report the numerical mean change or its uncertainty, so the primary outcome’s magnitude and precision cannot be interpreted from the record.

Even if the average change were available, it would describe change within a non-randomized, single-group study. It would not, by itself, establish that GSK1325760A caused the change. The absence of a comparator means that other explanations for changes over time cannot be separated using the study design. The unmasked design is another consideration when interpreting participant and investigator assessments.

The safety listings describe events recorded in the GSK1325760A group. They do not provide a controlled comparison, and the registry record does not report the denominators or all contextual details needed to interpret the listed percentages. These listings should therefore be understood as descriptive information rather than estimates of comparative risk.

The listed secondary outcomes indicate that the study also considered symptoms, functional status, clinical worsening, and physiological measures. Their presence in the registry does not establish that a particular result was observed, and the registry record does not provide numerical results for those endpoints.

In general, statistical significance and clinical importance are different questions. A statistical estimate describes a pattern in the analyzed data under its assumptions; clinical importance requires context about the measure and the size and relevance of the change. Since the primary numerical estimate and its uncertainty are not reported, neither question can be resolved for the primary endpoint from this record.

The study’s completed status and enrollment count describe its registry history, not the strength of evidence for an effect. A planning calculation based on an observed effect is also not a substitute for a reported outcome, and it is not observed power.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly specified functional endpoint and the limits of a single-group design. The primary outcome is defined as mean change in six-minute walk distance from baseline to Week 12, with the direction of subtraction stated. These details make the intended estimand—the average within-participant change in the analyzed population—understandable.

At the same time, the design is non-randomized, unmasked, and single-group. Such a design can describe what happened to measured outcomes among participants, but it lacks a concurrent control group for separating treatment-associated change from other influences. This distinction is central when interpreting before-and-after results and is not repaired by a larger number of measurements or by statistical summaries alone.

The record also makes the missing-data approach explicit: last observation carried forward. Naming an imputation method improves transparency, but interpretation still depends on the extent and reasons for missing data and on the method’s assumptions. Those details and sensitivity analyses are not reported in the registry record.

Finally, the registry identifies multiple secondary outcomes across symptoms, clinical status, and physiological measures. This breadth may make the study informative descriptively, but it also raises general questions about outcome prioritization and multiplicity. The record does not describe a strategy for addressing those questions.

These features illustrate why endpoint definitions, analysis populations, missing-data methods, and comparator structure need to be considered together. In this study, the primary outcome result itself is not numerically reported, so the record supports methodological description but not an estimate of the observed mean change.

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.

The main trial-specific limitation is the lack of a control group. The registry describes a non-randomized, single-group study with no masking. Any within-group change in the primary endpoint cannot be interpreted as a controlled treatment effect, because the design does not isolate treatment from other influences over time.

The enrollment was 25, but the registry record does not report the number included in the primary analysis or the number with observed Week 12 measurements. The Full Analysis Set excludes participants without a dose or without a post-dose efficacy assessment, and the record states that missing values were handled using last observation carried forward. The extent and pattern of missing data, reasons for missingness, and sensitivity analyses are not reported.

The primary outcome is defined in detail, but its numerical result is not reported in the registry record. Without the estimate and a measure of uncertainty, the magnitude, direction, and precision of the average change cannot be assessed. The registry record also does not report a detailed statistical analysis plan, a rationale for the enrollment target, or the trial’s own sample-size justification.

The record lists multiple secondary outcomes and reports 2 analyses, but does not describe outcome prioritization or a multiplicity strategy. The safety listing includes counts and event-term percentages, but the denominators and further context needed for comparative interpretation are not reported. Because the study has no comparator, the safety listings cannot provide a relative comparison with another group.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension — NCT00540436.
• Registry record last updated 2012-10-15; status last verified 2012-10.
• Results first posted 2009-11-10.
• 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

The registry record describes a completed Phase II study of GSK1325760A in pulmonary arterial hypertension. It was open-label, non-randomized, unmasked, and single-group, with an enrollment of 25. The listed study start was 2007-08 and primary completion was 2009-01.

The primary outcome was mean change from baseline in six-minute walk distance at Week 12, measured in meters. The analysis population was the Full Analysis Set, and missing values were handled using last observation carried forward. The record lists secondary outcomes covering exercise capacity, dyspnea, functional classification, clinical worsening, cardiac measures, and pulmonary hemodynamics, alongside safety and pharmacokinetic objectives.

The registry record does not report a numerical primary outcome result, a confidence interval, a detailed statistical analysis plan, or the trial’s sample-size rationale. Its design permits description of outcomes in the study group but does not provide a randomized treatment comparison.