A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Non-steroidal Therapy.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Non-steroidal Therapy. (NCT00603382), a randomized phase 2 study. The primary outcome is Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter Phase 2 study. It enrolled 599 participants with asthma and is listed as completed. The study compared four once-daily doses of GW685698X with placebo and with fluticasone propionate inhalation powder at 100 µg twice daily. Treatment lasted 8 weeks.

The primary outcome was change from baseline in trough evening FEV1 at Week 8. The registry also lists outcomes covering peak expiratory flow, symptom-free and rescue-free periods, withdrawal due to lack of efficacy, adverse events, oropharyngeal candidiasis, and blood-cell measures. The record lists 23 outcome measures and 5 analyses.

Some design details cannot be established from the registry record. The randomization ratio, allocation-concealment procedures, eligibility criteria beyond the population description, and the trial's original sample-size justification are not reported in the registry record. The original analysis plan, including any interim analyses and multiplicity strategy, is also not reported in the registry record. These omissions limit how fully the posted results can be placed in the context of the study's planned statistical decisions.

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: Participants (par.) meeting eligibility criteria at the Screening visit completed a 28-day Run-in Period for Baseline, safety evaluations and measures of asthma status. Par. were then randomized to an 8-week Treatment Period. Total 1459 par. were screened, 601 were randomized of which 598 par. received at least one dose of study treatment.

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 participants randomized to treatment who received at least one dose of study medication. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement (scheduled and unscheduled visits) was used to impute missing measurements.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8, measured over Baseline and Week 8.

The primary endpoint is the mean change from baseline in trough FEV1 at Week 8, measured in liters. FEV1 is the maximal amount of air that can be forcefully exhaled in one second. The registry describes trough FEV1 as the value measured at the end of the dosing interval, approximately 24 hours after the last study-drug administration. Measurements were taken electronically by spirometry in the evening, before the dose and before rescue bronchodilator use. The highest of 3 technically acceptable measurements was recorded.

Change was defined as the Week 8 value minus the baseline value; the Visit 3 assessment served as baseline. This lung-function measure provides a continuous numerical outcome, allowing the analysis to estimate average change and compare groups while accounting for baseline FEV1 and specified participant and treatment characteristics. It is used as the primary endpoint in this trial, but the registry does not establish how a particular change should be interpreted for an individual participant.

7. Results Posted in the Registry

• GW685698X 25 µg OD: mean 0.24 versus 0.14 on control; difference 0.10 (95% CI -0.02 to 0.22), standardized effect d = 0.25; z-test p = 0.092.
• GW685698X 50 µg OD: mean 0.27 versus 0.14 on control; difference 0.13 (95% CI 0.01 to 0.25), standardized effect d = 0.31; z-test p = 0.031.
• GW685698X 100 µg OD: mean 0.34 versus 0.14 on control; difference 0.20 (95% CI 0.09 to 0.32), standardized effect d = 0.49; z-test p = <0.001.
• GW685698X 200 µg OD: mean 0.37 versus 0.14 on control; difference 0.23 (95% CI 0.11 to 0.35), standardized effect d = 0.56; 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.

Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period

• 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 errors.
• Result:
  • GW685698X 25 µg OD: mean 23.60 versus 9.60 on control; difference 14.00 (95% CI 2.39 to 25.61), standardized effect d = 0.34; z-test p = 0.018.
  • GW685698X 50 µg OD: mean 30.30 versus 9.60 on control; difference 20.70 (95% CI 9.15 to 32.25), standardized effect d = 0.51; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for GW685698X 25 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for GW685698X 50 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period

• 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 errors.
• Result:
  • GW685698X 25 µg OD: mean 27.20 versus 13.60 on control; difference 13.60 (95% CI 1.82 to 25.38), standardized effect d = 0.33; z-test p = 0.024.
  • GW685698X 50 µg OD: mean 33.50 versus 13.60 on control; difference 19.90 (95% CI 8.20 to 31.60), standardized effect d = 0.48; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for GW685698X 25 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for GW685698X 50 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline in the Percentage of Symptom-free 24 Hour (hr) Periods During the 8-week Treatment Period

• 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 errors.
• Result:
  • GW685698X 25 µg OD: mean 25.30 versus 18.40 on control; difference 6.90 (95% CI -1.94 to 15.74), standardized effect d = 0.22; z-test p = 0.126.
  • GW685698X 50 µg OD: mean 31.10 versus 18.40 on control; difference 12.70 (95% CI 3.90 to 21.50), standardized effect d = 0.41; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between GW685698X 25 µg OD and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for GW685698X 50 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The numerical secondary results available in the registry cover evening and morning peak expiratory flow and change in the percentage of symptom-free 24-hour periods. Across these outcomes, the posted estimates generally show larger mean changes in several active-treatment groups than in placebo. That broad pattern is directionally consistent with the primary endpoint estimates, but secondary outcomes assess different aspects of asthma and do not independently confirm the primary comparison.

The secondary findings should be read as supportive and exploratory rather than as a collection of equally definitive tests. The record lists 22 posted secondary outcomes, and there are multiple treatment groups and outcomes to consider. Without a reported multiplicity strategy, repeated unadjusted comparisons increase the chance that some apparently notable results arise by chance. The original plan for handling multiple secondary tests is not reported in the registry record.

Only a subset of the secondary outcomes is numerically detailed in the registry record used for these comparisons. The record also lists outcomes concerning rescue-free periods, withdrawal for lack of efficacy, adverse events, candidiasis, and blood-cell measures. No inference should be made about unreported numerical results from the mere presence of an outcome title. Overall, the secondary pattern provides context for the primary lung-function findings, but it does not remove the uncertainty in those findings or establish a separate treatment conclusion.

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

• Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period
• Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period
• Mean Change From Baseline in the Percentage of Symptom-free 24 Hour (hr) Periods During the 8-week Treatment Period
• Mean Change From Baseline in the Percentage of Rescue Free 24-hour (hr) Periods During the 8-week Treatment Period
• Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period
• Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period
• Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis
• Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is described as an analysis of covariance, or ANCOVA. In general, ANCOVA compares outcome values or changes between groups while adjusting for specified covariates. The registry says the model included baseline trough FEV1, country, sex, age, and treatment group. Accounting for baseline measurements can help distinguish treatment-group differences from differences in starting values. The posted record does not provide the fitted model details beyond this description.

What does the endpoint estimate represent?

The primary outcome is continuous, and the posted arm estimates are least-squares means with standard errors. In general, a least-squares mean is a model-based group estimate, adjusted according to the analysis model; it is not necessarily the raw arithmetic average. A standard error describes the estimated precision of a mean. It is different from a standard deviation, which describes variation among individual measurements. The registry provides the arm estimates and standard errors, but not individual participant data.

The registry defines the primary change as the Week 8 FEV1 minus the Visit 3 baseline FEV1. It identifies the analysis population as all randomized participants who received at least one dose of study medication. The record also states that last observation carried forward was used for missing data: the last non-missing post-baseline on-treatment measurement was used to impute a missing value. The description ends before fully specifying which scheduled and unscheduled measurements were eligible, so that detail is not reported in the registry record.

How should the group comparisons be read?

A mean difference expresses the estimated contrast between a treatment group and placebo in the endpoint's units, here liters. A positive reported difference indicates a greater estimated change in that group than in placebo. The sponsor's reported comparisons use ANCOVA and provide 95% confidence intervals and p-values. The registry labels some reported estimates as median differences and others as mean differences, even though the primary arm summaries are least-squares means. That mixed labeling is part of the reported record and should not be silently harmonized.

The additional recalculations are simple, unadjusted comparisons made from posted summary statistics. They are not the sponsor's ANCOVA. Their pooled standard deviations are described as approximate, and their p-values are unadjusted. Because the registry indicates a discrepancy, the sponsor's own analysis takes precedence when describing the trial's reported inferential results. The recalculations can still serve as a transparent check on the direction and approximate size of contrasts, but they do not replace the reported analysis.

What does a p-value contribute?

In general, a p-value measures how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The p-values in the sponsor comparisons should be read alongside their effect estimates and confidence intervals. The registry record does not report whether the primary comparisons were adjusted for multiple testing, so the listed p-values should not be treated as multiplicity-adjusted unless the record says so.

Why can missing-data choices matter?

In general, last observation carried forward fills a missing endpoint using an earlier recorded value. This can preserve participants in an analysis but assumes that the carried-forward measurement is an appropriate stand-in for the unavailable value. If change over time continues after the last measurement, or if missingness relates to outcome, that assumption may be imperfect. The record reports use of this method, but does not give enough detail to assess the pattern of missing measurements or the sensitivity of the primary result to alternative assumptions.

Likewise, an analysis population defined by randomization and receipt of at least one dose is not identical to every possible intention-to-treat definition. The registry supplies its own wording for the population; the full handling of participants who did not receive study medication is not reported in the registry record. These analytical details matter when interpreting precision and generalizability, and they are not resolved by the numerical estimates alone.

11. Confidence Intervals and Precision

The sponsor's 95% confidence intervals quantify uncertainty in the reported comparisons with placebo. In general, a confidence interval gives a range of effect estimates compatible with the data and analysis at the stated confidence level. It is not a guarantee that the true effect lies in the interval, and it does not describe the range of outcomes among individual participants.

For the 50 µg, 100 µg, and 200 µg GW685698X comparisons, the sponsor-reported intervals are entirely above zero: 0.011 to 0.247 liters, 0.089 to 0.319 liters, and 0.111 to 0.349 liters, respectively. The 25 µg interval runs from -0.018 to 0.221 liters, and the fluticasone interval runs from -0.010 to 0.223 liters; both include zero. An interval including zero means that the reported data and model do not rule out a zero contrast at that confidence level. It does not demonstrate that the groups are identical.

Interval width reflects precision as well as the scale of the outcome. These intervals still allow a range of plausible comparison values, and the registry does not state a threshold for interpreting the clinical importance of a difference in liters. The simple recalculated intervals are based on posted summary statistics rather than the sponsor's ANCOVA; where the record identifies a discrepancy, the sponsor's analysis is the primary source for interpretation.

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 trial's original design justification. They are expressed as participants per arm for the comparisons shown. The calculation assumptions are 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 as the effect to detect. The record's note says that time-to-event calculations, if present, would be total event counts; these comparisons are continuous outcomes, so their figures are participants per arm.

The 80% power column gives an estimated per-arm sample size for a future study to have an 80% chance of detecting the specified effect under those assumptions, if that effect is real. The 90% power column gives the corresponding planning target for a 90% chance. These are design probabilities under a model, not probabilities that the observed result is true. Smaller effects require more participants to detect, which is why the planning figures rise when the assumed effect is reduced to 75% or 50% of the observed effect.

These figures are not observed power. They are prospective planning illustrations and do not explain why this trial enrolled its actual number of participants. The original sample-size assumptions and justification are not reported in the registry record.

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 = 0.102; pooled standard deviation σ = 0.414.
2. n = 2 × (1.96 + 0.842)² × 0.414² / 0.102² = 258.4, rounded up to 259 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 <- 0.102                      # observed difference in means
sigma <- 0.413862284967982                     # 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(603382)
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 = 259 (80% power), 346 (90% power)
 75% of observed effect: n per arm = 460 (80% power), 616 (90% power)
 50% of observed effect: n per arm = 1,034 (80% power), 1,384 (90% power)
power.t.test: 259.4 
Simulated power at n = 259 per arm: 0.802 (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 reports sponsor ANCOVA comparisons for each active-treatment group against placebo. Those are the trial's own analyses and take precedence over the simple recalculations from posted summary statistics because a discrepancy is flagged in the record.

The sponsor's reported differences are 0.101 liters for GW685698X 25 µg, 0.129 liters for 50 µg, 0.204 liters for 100 µg, 0.230 liters for 200 µg, and 0.106 liters for fluticasone. The corresponding reported p-values are 0.095, 0.033, <0.001, <0.001, and 0.074. The sponsor labels the 25 µg and 100 µg contrasts as median differences and the other comparisons as mean differences. The registry does not explain this variation in labels.

The recalculated values are unadjusted and use posted summaries rather than the described ANCOVA model. They can help readers see how a simple contrast relates to the arm-level estimates, but should not be substituted for the sponsor's results. Differences between the two sets may reflect the distinct calculations and summary-statistic inputs; the registry record does not give a fuller explanation of the discrepancy.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical comparisons are made. In general, the more tests conducted, the greater the opportunity for some results to appear unusual by chance, even if all null hypotheses are true. This trial compares multiple GW685698X doses and fluticasone with placebo, and the record lists many secondary outcomes. The sponsor's reported p-values are presented without a stated adjustment. Whether a hierarchy, family-wise error procedure, false-discovery approach, or other strategy was planned is not reported in the registry record.

This absence matters when interpreting individual p-values, particularly among secondary outcomes. A p-value below a conventional threshold is not by itself proof of a robust finding, and unadjusted tests across many endpoints should be considered with restraint. The record does not state whether the primary endpoint comparisons were protected by a prespecified testing sequence or whether some comparisons were exploratory.

Missing-data handling is partly described. The primary population includes randomized participants who received at least one dose, and last observation carried forward was used for missing post-baseline values. The full operational details of the imputation rule are truncated in the record. Counts and patterns of missing primary measurements, reasons for missingness, and sensitivity analyses under alternative missing-data assumptions are not reported in the registry record.

The record's population definition and missing-data method therefore help explain how the posted endpoint estimates were produced, but do not fully establish how robust they are to exclusions or missingness assumptions. The original statistical analysis plan, protocol-specific decision rules, and interim-analysis procedures are not reported in the registry record. They should not be inferred from the posted p-values or from the fact that the trial is marked complete.

16. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: snake bite (1.0%), gastritis (1.0%), chest pain (1.0%), hyperhidrosis (1.0%), hypertension (1.0%).

The registry lists serious adverse events by treatment group. Serious events affected 0 of 94 participants in the placebo group, 1 of 97 in the GW685698X 25 µg group, 0 of 100 in the 50 µg group, 1 of 110 in the 100 µg group, 0 of 95 in the 200 µg group, and 2 of 102 in the fluticasone group. These are counts of participants affected, not measures of comparative risk adjusted for follow-up or other factors.

The registry also lists other on-treatment adverse events: 11 participants in placebo, 6 in the 25 µg group, 8 in the 50 µg group, 17 in the 100 µg group, 9 in the 200 µg group, and 16 in the fluticasone group. The registry record does not report death counts. Serious adverse-event counts alone do not establish whether treatments differ in safety; interpretation is limited by the study's size, duration, event types, and the absence of a detailed comparative analysis in the posted information.

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

The posted results describe average changes in trough FEV1 during an 8-week trial and comparisons with placebo. The sponsor's ANCOVA estimates favor a larger change relative to placebo for the 50 µg, 100 µg, and 200 µg GW685698X groups, with confidence intervals that exclude zero. The intervals for the 25 µg GW685698X and fluticasone comparisons include zero. These statements describe the reported statistical estimates; they do not establish what an individual participant would experience.

The results do not establish that all doses have a similar effect, that one dose is superior to another, or that the observed group-level pattern would persist in other populations or over a longer period. The registry reports no formal direct comparisons between active doses. It also does not provide a threshold for deciding whether a particular difference in FEV1 is clinically important. Statistical evidence and clinical importance are distinct questions.

Nor do the posted results settle the broader benefit-risk profile. The safety counts describe events during the study, but the registry does not report deaths and provides limited information for comparing event rates. The study's 8-week treatment period and Phase 2 designation are relevant context, not grounds for conclusions beyond the endpoints and follow-up described. No medical advice or treatment recommendation follows from these statistical summaries.

18. Why This Trial Matters Statistically

This trial illustrates several recurring statistical issues in clinical research. Its primary endpoint is a continuous lung-function measure analyzed with ANCOVA, so interpretation depends on both the estimated group contrast and its uncertainty. The record makes it possible to distinguish the sponsor's adjusted analysis from simple unadjusted recalculations based on summary statistics. That distinction is important: calculations that look similar in name may not estimate the same quantity or use the same modeling assumptions.

The result also shows why confidence intervals add information beyond a thresholded p-value. They indicate the range of comparison values compatible with the sponsor's analysis and make clear that estimates have varying precision. At the same time, the multiplicity of dose comparisons and secondary outcomes means individual unadjusted p-values should not be read in isolation. The registry does not state how the original analysis plan addressed that issue.

Finally, the stated use of last observation carried forward and the incomplete description of its implementation highlight how missing-data choices are part of an endpoint's meaning. Statistical conclusions depend not only on the outcome definition, but also on the population analyzed, model, missing-data approach, and prespecified testing strategy. Several of those details are only partly available in this registry record.

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.

Important limitations specific to this record include the discrepancy between the simple recalculations and the sponsor's reported analyses. The sponsor's analysis takes precedence, but the record does not explain the discrepancy in detail. The sponsor's own analysis labels some contrasts as median differences and others as mean differences, while the posted arm estimates are least-squares means. This mixed reporting makes the estimand less straightforward to describe consistently.

The analysis description is incomplete. The primary endpoint population and use of last observation carried forward are stated, but the imputation description is cut off and the record does not provide missing-data counts, reasons, or sensitivity analyses. The original sample-size rationale, detailed statistical analysis plan, multiplicity procedures, and interim-analysis information are not reported in the registry record.

The study lasted 8 weeks, and the record identifies it as Phase 2. The posted safety summary provides participant counts for serious and other adverse events but does not report death counts. Numerical detail is available for only some of the listed secondary outcomes. These limitations constrain assessment of longer-term outcomes, the full secondary-outcome pattern, and the robustness of statistical findings. They do not by themselves determine whether a reported estimate is valid, but they limit what can be concluded from the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Non-steroidal Therapy. — NCT00603382.
• Registry record last updated 2018-04-18; status last verified 2018-03.
• Results first posted 2013-08-19.
• 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

This completed, randomized, double-blind, parallel-group Phase 2 trial enrolled 599 adolescent and adult participants with asthma symptomatic on non-steroidal therapy. It compared four once-daily GW685698X doses and fluticasone propionate 100 µg twice daily with placebo over 8 weeks.

The primary outcome was change from baseline in evening trough FEV1 at Week 8. Sponsor-reported ANCOVA comparisons found intervals excluding zero for the 50 µg, 100 µg, and 200 µg GW685698X groups, but not for the 25 µg group or fluticasone comparison. A discrepancy with simple unadjusted recalculations is flagged, so the sponsor analysis takes precedence. Multiplicity handling, the original sample-size justification, and several details of missing-data implementation are not reported in the registry record.