This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants (NCT03276052), a non-randomized phase 1 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03276052 |
| Phase | Phase 1 |
| Condition | Healthy Volunteers |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Healthy Chinese male and female participants. The registry record lists an enrollment of 20 and defines the pharmacokinetic analysis set as participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Intervention
Aclidinium Bromide 400 μg, administered by inhalation. The arm description specifies one inhalation from the 400 μg inhaler. The study investigated single and multiple doses, with the multiple-dose schedule described as twice daily.
Comparator
No comparator group is listed. The study is identified as non-randomized and single-group, so its design does not provide a like-for-like control comparison.
Primary question
What is the maximum observed plasma concentration, or Cmax, after single-dose and multiple-dose administration, as characterized from concentration-time curves on Day 1 and Day 9? The registry also identifies safety and tolerability as study objectives.
The central question is pharmacokinetic rather than a comparison of clinical benefit between treatments. Cmax describes the highest observed plasma concentration in an individual concentration-time profile. The record identifies the planned summary measure as a geometric mean, with geometric coefficient of variation as the dispersion measure. However, it does not report the resulting Cmax estimates or their variability. The endpoint description refers to measurements after single dose or multiple dose; the listed timeframe is Day 1 and Day 9.
The safety question concerns adverse events during exposure to aclidinium bromide. The record lists the number of participants with adverse events as a secondary outcome and presents adverse-event counts for the study group. Because there is no control group, those counts describe events recorded among participants receiving the study drug; they do not estimate a difference in risk versus another treatment or no treatment. The registry record does not report a comparative safety question or a treatment-effect estimate.
3. Trial Design
This was a Phase I, open-label, single-group study of aclidinium bromide in healthy Chinese participants. The registry record identifies AstraZeneca as the sponsor and the study status as completed. The listed enrollment is 20. The brief study description calls it single centre and states that healthy Chinese male and female participants received single and multiple twice-daily inhaled doses. The intervention is Aclidinium Bromide 400 μg, described as one inhalation from the 400 μg inhaler.
The design is non-randomized and has no masking. A single group means there is no listed concurrent comparator arm. The study therefore describes pharmacokinetic measurements and adverse events during exposure; it is not structured as a randomized comparison of aclidinium bromide against another treatment. An open-label design means masking was not used, as also indicated by the registry record. Whether any procedures were used to reduce measurement or reporting bias is not reported in the registry record.
The study dates in the registry record are 2021-10-14 for the start and 2021-11-26 for primary completion. The primary endpoint is maximum observed plasma concentration, with Day 1 and Day 9 identified as the timeframe. The record characterizes this endpoint as taken directly from each participant’s concentration-time curve after single dose or multiple dose. It defines the pharmacokinetic analysis set as those in the safety analysis set who received at least 1 dose.
The registry record does not report a sample-size justification, a detailed dosing calendar, or a statistical analysis plan. Although it describes the study as completed, completion status alone does not indicate that all outcomes or analyses have been posted. The record identifies 16 outcome measures and 0 analyses, but the primary Cmax result is not reported. Further details of the protocol, including any planned interim analyses, are not reported in the registry record.
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: The Screening period was of 21 days before randomization. Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
Overall Study
| Stage | Aclidinium Bromide 400 μg |
|---|---|
| STARTED | 43 |
| COMPLETED | 20 |
| NOT COMPLETED | 23 |
Reasons for not completing this period:
| Reason | Aclidinium Bromide 400 μg |
|---|---|
| Withdrawal by Subject | 5 |
| Screening failure (non-fulfilment of inclusion/exclusion criteria) | 18 |
Analysis population for the primary outcome, as defined in the registry: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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: The safety analysis set included all participants who received at least 1 dose of IP and for whom any safety post-dose data were available.
| Characteristic | Unit | Aclidinium Bromide 400 μg |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | years | 27.15 (SD 5.20) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 11 |
| Race/Ethnicity, Customized: Asian/Chinese | Participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax), measured over Day 1 and Day 9.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | pg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is maximum observed plasma concentration, abbreviated Cmax, measured in pg/mL. For each participant, Cmax is the highest plasma concentration observed on the concentration-time curve for the relevant dosing period. The registry record identifies Day 1 and Day 9 as the timeframe and describes characterization after single dose or multiple dose.
Pharmacokinetic endpoints describe how a drug concentration changes in the body over time. Cmax is used to characterize the peak concentration reached after administration. It captures the highest measured point in the observed profile, rather than the concentration at every time point or the total exposure over the full profile. As a general statistical point, a peak measure can be sensitive to the timing and frequency of sample collection: a measured maximum is the highest observed value, and may not coincide exactly with the true biological peak.
The registry identifies the geometric mean as the summary measure and geometric coefficient of variation as the dispersion measure. A geometric mean is a way to summarize positive, often right-skewed measurements using a multiplicative scale. The geometric coefficient of variation describes relative spread on that scale. These are general interpretations of the stated summaries; the registry record does not report the actual Cmax values, the geometric coefficient of variation, or uncertainty intervals.
The endpoint is relevant to the stated pharmacokinetic objective, but it does not by itself answer a comparative efficacy question. The record does not describe a clinical outcome as the primary endpoint. It also does not report the concentration-time observations or details needed to assess how the observed maximum was distributed across participants.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed Phase I study with pharmacokinetic and safety objectives in healthy Chinese participants. Its listed primary endpoint is Cmax on Day 1 and Day 9, summarized using a geometric mean and geometric coefficient of variation. Despite that endpoint definition, the record does not report a Cmax estimate, a measure of its variability, or an uncertainty interval. Consequently, the posted information does not establish the numerical peak plasma concentration or how precisely it was estimated.
The record identifies 20 participants as enrolled and defines the pharmacokinetic analysis set by receipt of at least 1 dose and inclusion in the safety analysis set. It does not report how many participants contributed to each Cmax summary, whether any observations were unavailable, or how deviations from the planned measurement schedule were handled. Enrollment should therefore not be treated as confirmation that every enrolled participant contributed to every endpoint.
The safety figures describe the study group: 0 participants were listed with serious adverse events among 20 at risk, 5 were listed in the other adverse-event category among 20 at risk, and deaths were listed as 0. These are descriptive counts, not estimates of comparative risk. With no control group, the record cannot distinguish events associated with study participation from background events or estimate how the counts compare with another treatment. The record does not list serious adverse-event terms.
Several design features shape what the data can answer. The non-randomized, single-group design is suitable for describing observations in participants exposed to the study drug, but it does not yield a randomized treatment contrast. Open-label conduct also means masking was absent; the registry record does not describe any additional safeguards for measurements or event reporting. Participants were healthy Chinese volunteers, so the record does not establish what the same measurements or event counts would be in a different population.
The record identifies 16 outcome measures but 0 analyses. It gives no primary endpoint result, inferential test, confidence interval, missing-data account, or multiplicity procedure. No conclusion about statistical significance or precision can be drawn from the endpoint definition alone. The appropriate interpretation is therefore limited to the design, analysis population definition, and descriptive adverse-event counts actually reported in the registry record. The completed status does not fill in missing outcome results.
9. Statistical Methods Explained
The statistical methods described by the registry record are limited. It names the primary endpoint, its summary scale, its dispersion measure, its assessment timeframe, and the definition of the pharmacokinetic analysis set. It does not report a detailed statistical analysis plan or numerical primary outcome results. The explanations below describe the meaning of the stated methods in general terms and distinguish them from analyses that are not reported.
What does Cmax measure?
Cmax is the maximum observed plasma concentration for a participant’s concentration-time profile. It is a direct summary of the highest measured concentration after administration, rather than an average across the entire profile. The registry describes Cmax as being taken directly from the individual concentration-time curve after single dose or multiple dose. The listed timeframe is Day 1 and Day 9, and the unit is pg/mL.
As a general statistical concept, a maximum is an order-sensitive summary: it depends on the observed values and can be affected by the timing of measurements. If measurements are sparse around the peak, the highest recorded concentration may not capture the true peak precisely. The registry record does not state the sampling schedule or provide concentration-time data, so the adequacy of sampling around the maximum cannot be assessed from the posted information.
Why use a geometric mean?
The registry specifies a geometric mean for Cmax. In general, geometric summaries are useful for positive measurements that vary multiplicatively or are right-skewed. They summarize values on a logarithmic scale and then express the central estimate back on the original scale. This differs from an arithmetic mean, which summarizes additive deviations. The choice of a geometric mean does not itself show that a particular distributional assumption was checked or met; such checks are not reported in the registry record.
The stated dispersion measure is geometric coefficient of variation. In general, it describes relative variability on a multiplicative scale and complements the geometric mean by indicating how dispersed measurements are around that summary. It is not an uncertainty interval for the mean. A confidence interval, by contrast, is a range calculated to express uncertainty in an estimated quantity under a specified statistical procedure. The registry record does not report a confidence interval for Cmax or the value of the geometric coefficient of variation.
Who is included in the pharmacokinetic analysis set?
The record defines the pharmacokinetic analysis set as participants in the safety analysis set who received at least 1 dose of aclidinium bromide. This definition links inclusion to both safety-set membership and exposure. It does not state how many participants met the definition or contributed measurements to each endpoint. It also does not explain how incomplete profiles, missed doses, or other protocol deviations were handled.
As a general principle, an analysis population should be interpreted according to its stated inclusion criteria. A population restricted to participants who received treatment can differ from all those enrolled. Without a reported flow of participants through enrollment, dosing, and analysis, the extent of any such difference is not known. The enrollment figure is not a substitute for an endpoint-specific analysis count.
What can the single-group design estimate?
A single-group study can describe observed concentrations and events in the participants who received the intervention. It cannot, without a comparator, estimate a treatment contrast against another group. Randomization is a method for creating comparable groups, while a control arm supplies the concurrent reference for a contrast. Neither is listed in this study: allocation is non-randomized and the model is single-group. Thus, any numerical measurements from this design would describe the observed group rather than an effect relative to an alternative.
Open-label conduct means that masking was absent. In general, lack of masking can matter for outcomes involving judgment or reporting, although the registry record does not describe the specific outcome-assessment procedures or their susceptibility to such influences. The primary pharmacokinetic endpoint is defined by measured concentrations; the record does not provide enough procedural detail to evaluate measurement safeguards.
What analyses are not documented?
The registry record does not report inferential tests, uncertainty intervals, model details, transformations beyond naming geometric summaries, covariate adjustment, or a statistical analysis plan. It does not report interim analyses, sample-size justification, or handling of missing observations. The record lists 16 outcome measures and 0 analyses, but does not explain whether all planned analyses were completed or why results are absent. Accordingly, no unreported analysis should be inferred from the endpoint definition or study completion status.
As a general concept, over-dispersion refers to observed variability exceeding what a statistical model expects. It matters because a model that underestimates variability can produce overly narrow uncertainty intervals or misleading tests. The registry record does not identify a count model or report evidence of over-dispersion, so this concept is not a claim about the study’s analysis.
Similarly, statistical significance is not a property that can be inferred from a study label or a sample-size figure. It depends on a reported estimate, its uncertainty, and the specified analysis. Here, the primary estimate and inferential results are not reported. The posted information therefore supports an explanation of the intended endpoint and methods, but not a re-analysis of the primary pharmacokinetic result.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies 16 outcome measures, including Cmax as the primary outcome and the number of participants with adverse events as a secondary outcome. It reports 0 analyses. It does not describe a multiplicity strategy, such as prioritizing a family of hypotheses or adjusting inference when several outcomes are tested. As a general statistical matter, examining multiple outcomes can increase the chance of at least one apparently unusual result if each is assessed separately. Whether that issue arose in this study cannot be determined from the registry record, because no set of inferential analyses is reported.
The record does not provide a missing-data summary for the primary endpoint or adverse-event outcomes. It does not say whether concentration measurements or event information were incomplete, how missing observations were handled, or whether any sensitivity analyses were planned. The pharmacokinetic analysis set is defined as participants in the safety analysis set who received at least 1 dose, but the record does not give the number included in endpoint-specific summaries. Thus, the enrollment figure alone does not establish the analysis denominator for Cmax.
The registry record also does not report whether the analysis plan distinguished confirmatory from exploratory outcomes, specified a hierarchy among endpoints, or addressed repeated measurements. These details are not reported in the registry record. Without them and without posted analyses, no claim about multiplicity control, missing-data bias, or the robustness of the endpoint results can be made.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Aclidinium Bromide 400 μg | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Aclidinium Bromide 400 μg | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Aclidinium Bromide 400 μg | 5 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Aclidinium Bromide 400 μg |
|---|---|---|
| Syncope | Nervous system disorders | 1 of 20 |
| Atrial escape rhythm | Cardiac disorders | 1 of 20 |
| Orthostatic hypotension | Vascular disorders | 1 of 20 |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | 1 of 20 |
| Mouth ulceration | Gastrointestinal disorders | 1 of 20 |
| Alanine aminotransferase increased | Investigations | 1 of 20 |
| Aspartate aminotransferase increased | Investigations | 1 of 20 |
The registry record lists serious adverse events for the Aclidinium Bromide 400 μg group. It reports 0 participants with serious adverse events among 20 at risk, 5 participants in the other adverse-event category among 20 at risk, and 0 deaths. These are descriptive figures for this single study group.
The serious-event count is not a comparison with an untreated group or another intervention. Because the design is single-group and non-randomized, these figures do not quantify a difference in event risk between treatments. The record does not list the terms of any serious adverse events; its list of top serious terms is empty. It also does not provide further detail about the events in the other category, their timing, severity, or relationship to study drug. The label of that category should not be taken to supply details that the record does not report.
In general, a count of observed events describes what was recorded during a study, while an estimate of comparative risk requires a defined comparison. The absence of reported serious events in this group should not be interpreted as proof that serious events cannot occur. Nor do the other-event figures establish causation. The registry record does not report follow-up details or an event-level account that would support broader safety conclusions.
12. What the Result Does, and Does Not, Mean
This study addresses pharmacokinetics and safety in healthy Chinese participants exposed to inhaled aclidinium bromide. Its primary endpoint is Cmax, assessed on Day 1 and Day 9 and intended to be summarized with a geometric mean and geometric coefficient of variation. The registry record provides the endpoint definition but not its numerical result. It therefore does not allow readers to assess the observed peak concentration or the precision and variability of that estimate.
The safety data report 0 participants with serious adverse events among 20 at risk, 5 with events in the other category among 20 at risk, and 0 deaths. These figures describe the recorded study group and do not provide a comparison with a control group. They do not establish that the intervention caused or prevented any event.
The study’s single-group, non-randomized design does not estimate a randomized treatment effect. Its open-label conduct means there was no masking. The participant population is described as healthy Chinese male and female participants, so the record does not establish whether results would apply to people with a medical condition or to other populations. The registry does not report the primary Cmax estimates, endpoint-specific analysis counts, uncertainty intervals, or a detailed account of missing observations.
In general, a Phase I pharmacokinetic study can characterize measured concentrations and record safety observations under the study conditions. That general purpose should not be confused with evidence of comparative clinical benefit. No efficacy conclusion is supported by the endpoint information, and the record does not state a clinical treatment comparison. The appropriate conclusion is bounded: the registry identifies the study question, design, outcome definition, and descriptive safety figures, while leaving the primary pharmacokinetic results and important analysis details unreported.
13. Why This Trial Matters Statistically
This study illustrates why design and reporting details matter when interpreting pharmacokinetic research. Cmax is a clearly identified concentration endpoint, and the record specifies a geometric mean and geometric coefficient of variation. Yet without the actual estimate, variability, and uncertainty, the endpoint definition alone cannot show what concentrations were observed or how precisely they were characterized. A specified measure is not a result.
The single-group structure also defines the inferential boundary. Measurements in the treated group can describe that group, but there is no concurrent control for estimating a treatment contrast. This distinction is important when interpreting safety counts: event totals are observations, not comparative estimates or evidence of causation. Non-randomized allocation and open-label conduct further reinforce the need to avoid reading the record as a controlled treatment-effect study.
The record gives an enrollment figure and defines the pharmacokinetic analysis population, but does not state how many participants contributed to each outcome. This highlights a general reporting principle: enrollment, treatment exposure, safety follow-up, and endpoint analysis can represent different populations. Reporting participant flow and endpoint denominators helps readers understand the basis of each estimate.
Finally, the record lists multiple outcome measures but no analyses, and does not report a statistical plan, missing-data handling, or multiplicity approach. Those omissions prevent assessment of how the intended analyses were carried out. The study remains interpretable as a description of its design and stated objectives, but its posted record does not support detailed statistical conclusions about the primary endpoint.
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 principal limitation for interpretation is that the registry record does not report the numerical primary endpoint result. Although it specifies Cmax, the measurement unit, summary approach, dispersion measure, and timeframe, it does not give the geometric mean, geometric coefficient of variation, or an uncertainty interval. No estimate of the observed pharmacokinetic profile can therefore be evaluated.
The study has a single-group, non-randomized design with no listed comparator and no masking. This prevents a controlled treatment comparison and limits interpretation of adverse-event counts. The healthy Chinese participant population is specifically identified; the record does not establish whether findings extend to other populations. The brief description identifies male and female participants, but further participant characteristics are not reported.
The record states an enrollment of 20 and defines the pharmacokinetic analysis set, but does not give endpoint-specific denominators or a participant-flow account. Missing measurements, withdrawals, protocol deviations, and their handling are not reported in the registry record. The concentration sampling schedule and details of how profiles were assessed are also not reported, limiting evaluation of the observed maximum.
The registry identifies 16 outcome measures and 0 analyses, while providing no detailed analysis plan, multiplicity procedure, interim-analysis information, or sample-size justification. The primary endpoint’s planned summary is stated, but no statistical test or model is described. These gaps mean the record supports a design-level reading and a limited description of safety figures, not an assessment of the precision, completeness, or robustness of the primary pharmacokinetic findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants — NCT03276052.
- Registry record last updated 2023-12-11; status last verified 2023-02.
- Results first posted 2023-12-11.
- 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.
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18. Record Summary
NCT03276052 is a completed Phase I, open-label, non-randomized, single-group study sponsored by AstraZeneca. It enrolled 20 healthy Chinese participants and investigated single and multiple twice-daily inhaled doses of Aclidinium Bromide 400 μg. The listed primary endpoint is maximum observed plasma concentration on Day 1 and Day 9, summarized using a geometric mean and geometric coefficient of variation.
The registry record defines the pharmacokinetic analysis set but does not report the primary endpoint estimate, its variability, or uncertainty. It lists 16 outcome measures and 0 analyses. Safety figures include 0 participants with serious adverse events among 20 at risk, 5 in the other adverse-event category among 20 at risk, and 0 deaths. With no comparator group, these are descriptive counts rather than comparative treatment effects.