The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen (NCT00999466), a randomized phase 2 study. The primary outcome is FEV1, Late Asthmatic Response (LAR) - Pre-treatment.

2. Clinical Question

The registry’s broad study objective was to investigate efficacy, tolerability, and safety of AZD8848 in people with allergic asthma challenged with an inhaled allergen. The primary outcome entry, however, is explicitly labeled as a pre-treatment measurement. That distinction matters: a baseline measure can characterize the groups before treatment, but by itself it cannot show whether the groups changed differently after receiving the study drug or placebo. The record lists several later FEV1 measures as secondary outcomes, but the primary comparison presented is not a post-treatment outcome.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase IIa study sponsored by AstraZeneca. The title describes a double-blind, placebo-controlled investigation of 8 intranasal doses of AZD8848 administered once weekly. The study is marked completed. Its registry enrollment is 60, while the brief summary states that the study would include 59 asthmatic patients in total; the registry record does not explain this difference.

The arm descriptions separate a Pilot part, with AZD8848 30 μg and placebo, from a Main part, with AZD8848 60 μg and placebo. The primary outcome record says that six AZD8848 30 μg participants and three placebo participants took part in the Pilot part only and did not have the outcome collected. The reported primary measure is instead based on Main-part participants who contributed outcome data: 22 for AZD8848 60 μg and 23 for placebo. The 30 μg primary outcome row has no analyzed participants or reported mean.

The registry lists allergic asthma as the condition and describes an inhaled-allergen challenge. The primary measure is a pre-treatment FEV1 response ratio. Secondary outcomes include early asthmatic response FEV1 measures at pre-treatment and after the last dose, as well as methacholine challenge measures at several time points. The record lists 90 outcome measures and 87 posted secondary outcomes, but those counts do not establish which results were prespecified as confirmatory or how multiplicity was handled.

The study start is recorded as 2009-10 and primary completion as 2011-02. Allocation concealment procedures, detailed randomization methods, the trial’s original sample-size justification, and the full statistical analysis plan are not reported in the registry record. The record also does not describe the specific masking procedures or whether masking was assessed during the study. Those details cannot be inferred from the design labels alone.

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.

Pilot Part

Main Part

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: There were 6 AZD8848 nasal spray 30 μg subjects and 3 placebo subjects participated in the Pilot part only that they did not have outcome measure collected. The number of participants analyzed for each outcome measure were subset of the subjects who participated in the Main part and also provided data for that measure.

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: AZD8848 30 μg nasal spray was only done in Pilot part. 3 of the 28 placebo subjects were from the PILOT part and 25 placebo subjects were from the MAIN part.

6. Primary Endpoint

The registry lists the primary outcome as FEV1, Late Asthmatic Response (LAR) - Pre-treatment, measured over Pre-treatment (Baseline measurement).

The primary outcome is titled “FEV1, Late Asthmatic Response (LAR) - Pre-treatment.” FEV1 is forced expiratory volume in 1 second. The registry defines the LAR measure as the ratio of the FEV1 area under the curve from 4-10 hour post allergen challenge, calculated using the trapezoidal formula and divided by time, to the pre-challenge FEV1 measurement. It is reported as a mean with standard deviation, and its unit is described as a ratio.

In general, a time-normalized area under a response curve summarizes the measured response across a stated interval rather than at a single instant. Dividing by the pre-challenge FEV1 expresses the response relative to the pre-challenge measurement. Such a measure can be useful when the research question concerns the pattern of lung function after allergen challenge, rather than only one isolated measurement. This explanation describes the general statistical interpretation of a ratio and area under a curve; it does not establish a clinical threshold or a meaningful difference for this study.

The timing label is decisive for interpretation: the primary outcome is marked pre-treatment. It can therefore describe the recorded baseline response in each analyzed group, but the posted primary measure does not itself quantify a post-treatment change or a treatment-by-time contrast. The registry record does not report a clinically important difference for this measure.

7. Results Posted in the Registry

• AZD8848, 60 μg: mean 0.81 versus 1.01 on control; difference -0.20 (95% CI -0.57 to 0.18), standardized effect d = -0.30; z-test p = 0.301.

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.

FEV1, Early Asthmatic Response (EAR) - Pre-treatment

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AZD8848, 60 μg: mean 0.52 versus 0.61 on control; difference -0.09 (95% CI -0.27 to 0.09), standardized effect d = -0.28; z-test p = 0.341.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD8848, 60 μg and the control. The interval gives the range of effects that remain compatible with the data.

FEV1, Early Asthmatic Response (EAR) - 1 Week After Last Dose

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AZD8848, 60 μg: mean 0.47 versus 0.62 on control; difference -0.16 (95% CI -0.37 to 0.06), standardized effect d = -0.43; z-test p = 0.148.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD8848, 60 μg and the control. The interval gives the range of effects that remain compatible with the data.

FEV1, Early Asthmatic Response (EAR) - 4 Weeks After Last Dose

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • AZD8848, 60 μg: mean 0.51 versus 0.59 on control; difference -0.08 (95% CI -0.28 to 0.12), standardized effect d = -0.25; z-test p = 0.424.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD8848, 60 μg and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary FEV1 summaries show group means for early asthmatic response at pre-treatment, one week after the last dose, and four weeks after the last dose. In each comparison, the reported AZD8848 60 μg mean is lower than the placebo mean, and each unadjusted interval includes no difference. These descriptive results are broadly consistent with the direction of the primary baseline comparison, but consistency in direction does not make them evidence of a treatment effect, especially when the primary endpoint is pre-treatment and the secondary measures have their own time points and uncertainty.

The secondary outcomes include a range of methacholine challenge measurements as well as FEV1 measures. The registry record lists 87 posted secondary outcomes, while the outcome list names assessments at multiple times and under pre- and post-allergen challenge conditions. This variety can help describe different aspects of response, but it also means individual findings should not be interpreted in isolation as confirmatory unless an analysis hierarchy or multiplicity approach is established.

The reported secondary comparison p-values are unadjusted, and the registry record does not report a correction across outcomes. In general, examining multiple outcomes increases the opportunity for chance findings to appear notable. Thus, secondary estimates are best read as exploratory descriptions of the posted data, with emphasis on their direction, uncertainty, timing, and analyzed population rather than on isolated p-values. No posted secondary result changes the fact that the primary measure is a pre-treatment assessment.

The record contains no formal reported-analysis entries for the secondary outcomes. It does not describe a prespecified order of testing or identify any secondary outcome as a confirmatory endpoint. Nor does it give clinical thresholds for judging the importance of the observed differences. The secondary results can therefore contribute context, but they do not by themselves establish a reliable treatment contrast or resolve the limitations of the primary endpoint’s timing.

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

• FEV1, Early Asthmatic Response (EAR) - Pre-treatment
• FEV1, Early Asthmatic Response (EAR) - 1 Week After Last Dose
• FEV1, Early Asthmatic Response (EAR) - 4 Weeks After Last Dose
• PC20 Methacholine Challenge - Pre-treatment, Pre Allergen Challenge
• PC20 Methacholine Challenge - Pre-treatment, Post Allergen Challenge
• PC20 Methacholine Challenge - 1 Week After Last Dose, Pre Allergen Challenge
• PC20 Methacholine Challenge - 1 Week After Last Dose, Post Allergen Challenge
• PC20 Methacholine Challenge - 4 Weeks After Last Dose, Pre Allergen Challenge

9. Statistical Interpretation

10. Statistical Methods Explained

What does the group mean describe?

The primary outcome is a continuous measure, summarized by a mean and standard deviation. A mean describes the center of the observed values in a group. A standard deviation describes how dispersed individual values are around that group mean. They answer different questions: the mean is an estimate of the group’s average measurement, while the standard deviation characterizes participant-to-participant variation. Neither quantity alone is a measure of the precision of a comparison between groups.

The analyzed primary data are listed for AZD8848 60 μg and placebo. The group means are 0.814 and 1.01, and their standard deviations are 0.45 and 0.784. The AZD8848 30 μg row contains no analyzed participants or value. This means the primary numerical comparison is not a three-group analysis and cannot be used to assess a dose-response pattern.

How should the mean difference be read?

The listed mean difference compares the mean in the AZD8848 60 μg group with the placebo mean. Its estimate is -0.196. A negative value means the first group’s reported mean is lower than the comparator group’s reported mean for this particular measure. The direction is descriptive; because the measure is pre-treatment, it is not an estimate of how treatment changed the outcome.

In general, a mean difference retains the original scale of the measured outcome, while a standardized effect expresses a difference in units of pooled variability. The registry record also contains a standardized effect value, but the clinical meaning of a standardized value depends on context and does not supply a clinical threshold. Neither form of summary changes the endpoint’s pre-treatment timing.

What does the confidence interval add?

A confidence interval is a range of values generated by a statistical procedure intended to reflect uncertainty in an estimate. In general, a wider interval indicates less precision than a narrower interval, all else being equal. For the primary comparison, the interval includes both negative and positive values. It therefore does not isolate a single direction of baseline difference. An interval including no difference is not proof that the groups are exactly alike, and it is not a test of equivalence unless a suitable equivalence framework and margin are specified.

The registry record does not report the confidence level or the complete statistical method used to derive the posted comparison interval. The estimate and interval can be described as presented, but a more detailed reconstruction of the sponsor’s analysis is not justified by the record. The unadjusted p-value is 0.301; it should be interpreted alongside the estimate and interval rather than as a measure of effect size or clinical importance.

Why does the analysis population matter?

The primary outcome description says that analyzed participants were a subset of people who participated in the Main part and also provided data. It also notes that Pilot-part participants did not have this outcome collected. The record does not specify a full analysis-population definition, such as whether all randomized Main-part participants were included regardless of adherence, or how missing measurements were handled. Consequently, the displayed group summaries describe the participants with reported outcome data, not necessarily every randomized participant.

Missing outcome values can affect interpretation if the chance of having a measured result is related to the outcome or differs across groups. General approaches to missing data make different assumptions, and complete-case summaries can be affected when those assumptions are not met. The registry record does not report imputation, sensitivity analyses, or reasons for missing primary outcome data beyond the Pilot-part note. No specific direction or size of missing-data bias can be determined from this information.

What can randomization and masking support?

Random allocation is intended, in general, to reduce systematic differences between assigned groups at baseline. Masking is intended to reduce the influence of treatment knowledge on care, measurement, or reporting. The record classifies the study as randomized and quadruple-masked, but it does not detail the random sequence generation, allocation concealment, or who was masked. Moreover, the analyzed primary comparison is explicitly pre-treatment and is limited to participants with outcome data. The design labels alone cannot resolve the effects of those restrictions.

The study is described as parallel-group and placebo-controlled. A parallel-group comparison contrasts participants assigned to different groups rather than comparing each participant with their own outcome under another assignment. General statistical validity depends on suitable analysis and implementation as well as the design label. The registry record does not report enough detail to assess all of those elements.

What does the record say about the statistical plan?

The registry record does not report the original sample-size justification, a detailed statistical analysis plan, interim analyses, or a prespecified multiplicity procedure. It lists no formal analyses in the reported-analysis entries, although it does contain outcome summaries and a comparison. The absence of a detailed plan means it is not possible to establish from the record which analysis decisions were prespecified, how covariates were selected, or whether other planned analyses were not posted.

The displayed p-value is explicitly unadjusted. In general, when several outcomes or comparisons are examined, the chance of at least one apparently notable result can rise unless the analysis accounts for multiplicity or the results are interpreted as exploratory. The record lists many outcome measures, but does not say whether the primary and secondary outcomes formed a formal testing hierarchy. This makes cautious interpretation appropriate, particularly for secondary results.

11. Confidence Intervals and Precision

The primary difference estimate is -0.196, and its confidence interval extends from a negative value to a positive value. This interval includes no difference, so the posted result does not pin down a single direction for the baseline comparison. Its span indicates that the data are compatible with a range of values rather than a narrowly estimated difference. The registry record does not report a clinical threshold against which to judge whether any value in that range would matter clinically.

Precision is distinct from statistical significance and from clinical importance. A confidence interval describes uncertainty under the statistical procedure used; it does not indicate the probability that the true value lies inside the particular interval. In general, more variable measurements and smaller analyzed groups tend to yield less precise estimates, though the exact effect depends on the analysis and data. Here the primary summaries report standard deviations of 0.45 and 0.784, with 22 participants in the AZD8848 60 μg group and 23 in placebo.

The lack of primary outcome data for the AZD8848 30 μg Pilot group also limits what can be estimated across the study arms. The primary result does not offer a precision estimate for that group or a comparison of the two AZD8848 dose levels. Further, the record does not state the confidence level or full interval method, so interpretation should remain at the level of the posted estimate and interval rather than imply additional properties of the calculation.

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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect in the posted comparison, not the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect equal to the stated fraction of the observed effect. The registry record does not report the assumptions used for the original trial design or its sample-size justification.

The 80% power column gives the estimated participants per arm under those assumptions for an analysis to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses a higher target chance of detection and therefore requires more participants per arm under the same assumptions. These are planning concepts, not guarantees for a future study: actual precision and detection depend on the true effect, variability, missing data, analysis choices, and other features.

Rows that plan for 75% or 50% of the observed effect represent smaller effects than planning for 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants under the stated assumptions. The resulting figures are hypothetical illustrations tied to this observed estimate, not a recommendation or reconstruction of the AZD8848 study’s original design. This is not observed power.

The accompanying curve should be read in the same planning context: it relates the chosen effect size and participant count to the modeled power under the stated assumptions. It does not display a new observed outcome or establish the actual power of the completed trial. The figures apply to the 60 μg versus placebo comparison used for the illustration, not to the Pilot group, which has no primary outcome data.

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 = -0.196; pooled standard deviation σ = 0.643.
2. n = 2 × (1.96 + 0.842)² × 0.643² / -0.196² = 168.9, rounded up to 169 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 <- -0.196                      # observed difference in means
sigma <- 0.64293896415438                     # 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(999466)
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 = 169 (80% power), 227 (90% power)
 75% of observed effect: n per arm = 301 (80% power), 403 (90% power)
 50% of observed effect: n per arm = 676 (80% power), 905 (90% power)
power.t.test: 169.9 
Simulated power at n = 169 per arm: 0.798 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists 90 outcome measures and 87 posted secondary outcomes, spanning multiple FEV1 and methacholine challenge assessments. It does not report whether these outcomes were organized into a prespecified testing hierarchy, whether the primary outcome had a protected testing sequence, or whether any multiplicity adjustment was planned or applied. The primary comparison is accompanied by an unadjusted p-value, and the secondary comparisons are also described as unadjusted. Their p-values should not be read as if they accounted for the full set of outcomes.

In general, multiplicity matters because testing many outcomes can increase the chance that at least one result appears unusual under a no-effect model. A prespecified strategy can control or otherwise manage that issue, but different strategies answer different questions. Since the registry record does not report such a strategy, the secondary findings have less confirmatory weight and should be treated cautiously. This limitation does not establish that any particular result is false; it means the record does not show how the family of tests was handled.

The primary outcome population is described as a subset of Main-part participants who provided outcome data. The record notes that six AZD8848 30 μg Pilot participants and three placebo Pilot participants did not have this outcome collected. It does not fully define the analysis population, state the number randomized to each group, give reasons for missing primary data beyond the Pilot-part note, or describe a missing-data method. There is no reported imputation procedure or sensitivity analysis for missing values.

These omissions matter because the summaries may represent only participants with observed measurements. In general, if missingness is associated with the outcome or differs across treatment groups, an analysis limited to observed values can be misleading. The available record does not show whether such concerns occurred or in which direction they might operate. It also does not report a detailed statistical analysis plan, interim analyses, or the original sample-size justification, so the analysis decisions cannot be fully assessed.

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

The posted primary result describes a difference in mean pre-treatment FEV1 LAR ratio between the AZD8848 60 μg Main-part group and placebo. The reported means were 0.814 and 1.01, and the listed mean difference was -0.196. The unadjusted p-value was 0.301, and the interval includes no difference. These results do not identify a clear, precise baseline separation between the analyzed groups.

They do not establish whether AZD8848 changes the late asthmatic response after treatment. The endpoint is explicitly pre-treatment, so it is a baseline measure, not a post-treatment treatment-effect estimate. The study’s title and objective describe an investigation of efficacy, tolerability, and safety, but the primary data posted in this record do not answer every part of that objective. Post-treatment FEV1 measures appear among the secondary outcomes and must be considered separately.

The primary result also does not show that AZD8848 and placebo are equivalent. A non-significant unadjusted p-value is not an equivalence test, and the registry record does not report an equivalence margin or a clinical importance threshold. The interval’s inclusion of no difference indicates uncertainty, not proof that all potentially relevant differences have been excluded.

Nor does this primary comparison provide a dose comparison. The 30 μg Pilot group has no primary outcome value, so the posted primary result only contrasts 60 μg with placebo. It cannot show whether one dose differs from another, or whether the observed summaries vary systematically with dose.

The record includes adverse-event summaries, but denominators at risk are not reported for the groups. It lists serious adverse events of 0 for AZD8848 30 μg, 0 for AZD8848 60 μg, and 1 for placebo, along with other adverse events of 6, 22, and 24 respectively. Without group denominators and additional context, those counts should not be converted into comparative rates. They do not alone establish a safety difference. Overall, the registry record supports a description of the posted measurements and their uncertainty, not a clinical recommendation or a definitive conclusion about treatment benefit or harm.

16. Why This Trial Matters Statistically

This study illustrates why the timing and definition of an endpoint are as important as its name. The primary outcome is a physiologically interpretable FEV1 response ratio, but its label specifies a pre-treatment measurement. Treating it as a treatment-effect outcome would confuse a baseline group comparison with a comparison of responses after assignment. That distinction is essential when reading registry results, especially when the study’s broad objective refers to efficacy.

It also illustrates how registry reporting can constrain statistical interpretation. The study is described as randomized and masked, yet the available primary analysis includes only the 60 μg Main-part group and placebo; the 30 μg Pilot-part outcome is unavailable. The registry record does not fully define the analysis population or describe missing-data methods. A reader therefore needs to distinguish what the group summaries show from what they cannot establish about all randomized participants or all assigned arms.

The primary estimate is accompanied by an interval that crosses no difference and an unadjusted p-value. Considering these together discourages overreliance on a binary p-value threshold. The interval conveys that the estimated baseline difference is imprecise, while the p-value does not measure clinical importance or the probability that a treatment effect exists. The lack of reported multiplicity procedures also makes restraint important when considering the many secondary outcomes.

Finally, planning illustrations based on the observed effect show how sample-size requirements depend on the effect a future study aims to detect. They are not evidence about the power achieved in this completed study, nor do they replace the unreported original design justification. The statistical lesson is to keep endpoint timing, analyzed population, uncertainty, multiplicity, and planning assumptions distinct when interpreting a clinical-trial record.

17. 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 most consequential endpoint-specific limitation is that the primary measure is labeled pre-treatment. It describes a baseline measurement rather than a post-treatment outcome, so it cannot serve as a direct estimate of the treatment effect. Although post-treatment FEV1 assessments are listed as secondary outcomes, the primary result does not summarize those changes.

The 30 μg Pilot group has no primary outcome data. The registry record says that six AZD8848 30 μg participants and three placebo Pilot participants did not have the outcome collected, while the reported primary summaries concern Main-part participants who provided data. The record does not give a primary outcome value for the Pilot group or a complete explanation of which participants were eligible for each analysis. The enrollment figure is 60, whereas the brief summary says 59 participants in total; the record does not reconcile these statements.

Several details needed for stronger assessment are not reported in the registry record: the original sample-size justification, the detailed statistical analysis plan, interim analyses, the complete analysis-population definition, and handling of missing outcome data. The record does not describe the interval calculation method or report a clinically important threshold for the ratio. It also does not state whether multiplicity was addressed across the large set of outcomes.

Adverse-event denominators at risk are not reported. Consequently, the posted counts cannot be interpreted as group-specific rates or compared as if exposure time and ascertainment were equivalent. The registry record also does not give enough information to interpret the listed serious adverse event term beyond its reported percentage. These limits apply to interpretation of the posted record; they do not establish that the study did not collect or analyze additional information.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen — NCT00999466.
• Registry record last updated 2016-02-26; status last verified 2016-01.
• Results first posted 2016-01-26.
• 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.

21. Record Summary

The registry identifies NCT00999466 as a completed Phase IIa randomized, quadruple-masked, parallel-group study sponsored by AstraZeneca. It concerns intranasal AZD8848 and placebo in mild to moderate allergic asthma during inhaled-allergen challenge. The official title describes 8 once-weekly doses.

The primary posted outcome is the pre-treatment FEV1 Late Asthmatic Response ratio. Its mean was 0.814 for AZD8848 60 μg and 1.01 for placebo; the listed mean difference was -0.196, with an unadjusted p-value of 0.301. The endpoint is a baseline measure, and the comparison interval includes no difference. The 30 μg Pilot group has no primary outcome data.

The registry record lists numerous secondary outcomes but does not report a multiplicity procedure, a complete analysis plan, or details of missing-data handling. It reports enrollment of 60, while the brief summary states 59 participants in total, without explaining the discrepancy. Interpretation should remain focused on the posted data, their timing, and the limitations of the analysis information in the record.