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 Study to Estimate Effect of 4 Different Doses of AZD3355 on Reflux Episodes, Which Patients With Gastroesophageal Reflux Disease (GERD) May Experience (NCT01043185), a randomized phase 2 study. The primary outcome is Total Number of Reflux Episodes During 24 Hours.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01043185 |
| Phase | Phase 2 |
| Condition | Gastroesophageal Reflux Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 27 |
| Arms in the primary outcome | 5 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with gastroesophageal reflux disease (GERD) who continued to experience symptoms despite proton pump inhibitor (PPI) treatment. The registry reports an enrollment of 27 and describes the primary endpoint population as the Efficacy Analysis Set (EAS). It does not give further participant characteristics in this record.
Intervention
The active study treatment was AZD3355 at four listed doses: 30 mg, 90 mg, 120 mg, and 240 mg. The registry describes the investigation as a pharmacodynamic study estimating the dose-response relationship for reflux episodes.
Comparator
Placebo was the listed control treatment. The study is described as placebo-controlled, randomized, triple-masked, and crossover. The registry does not report the treatment sequences or details of how treatment periods were assigned.
Primary question
The primary question was how AZD3355 dose related to the total number of reflux episodes recorded over 24 hours. The registry reports geometric-mean estimates and 95% confidence intervals for each listed treatment, but does not report a formal statistical comparison or a dose-response test. The estimates describe the posted endpoint data; by themselves, they do not establish whether differences between treatments are statistically distinguishable.
3. Trial Design
The registry describes NCT01043185 as a randomized, triple-masked, placebo-controlled, Phase IIA pharmacodynamic study with a crossover model. It was sponsored by AstraZeneca and is listed as completed. The record gives an enrollment of 27, with a start date of 2009-12 and primary completion in 2010-05.
The study compared four AZD3355 dose groups—30 mg, 90 mg, 120 mg, and 240 mg—with placebo. Its official title calls it a 4-way crossover study, and the primary endpoint description refers to measurements during 24 hours at four different visits, with a 7-28 days interval between visits. The registry does not describe the treatment sequence, the allocation procedure beyond randomization, or the details of masking. The listed treatment groups and the description of the crossover design do not establish how each participant experienced the treatment periods.
The registry’s stated purpose was to estimate the effect of the four AZD3355 doses on reflux episodes in patients with GERD who had a partial response to PPI treatment. Its primary endpoint was total reflux episodes during 24 hours, assessed by ambulatory impedance-pH recording. Three secondary outcomes are listed: acid reflux episodes, weakly acidic reflux episodes, and weakly alkaline reflux episodes. The record does not report a statistical analysis plan, sample-size justification, or formal endpoint comparison results.
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.
Only the first 6 of 10 groups are shown.
Period 1 - First Intervention
| Stage | First 30mg, Then 90mg, Then 120mg, Then Placebo | First 30mg, Then 90mg, Then Placebo, Then 120mg | First 120mg, Then Placebo, Then 240mg, Then 90mg | First Placebo, Then 30mg, Then 90mg, Then 120mg | First 90mg, Then Placebo, Then 120mg, Then 240mg | First Placebo, Then 240mg, Then 90mg, Then 30mg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 2 | 3 | 2 | 2 | 3 |
| COMPLETED | 3 | 2 | 3 | 2 | 2 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period 2 - First Washout Period
| Stage | First 30mg, Then 90mg, Then 120mg, Then Placebo | First 30mg, Then 90mg, Then Placebo, Then 120mg | First 120mg, Then Placebo, Then 240mg, Then 90mg | First Placebo, Then 30mg, Then 90mg, Then 120mg | First 90mg, Then Placebo, Then 120mg, Then 240mg | First Placebo, Then 240mg, Then 90mg, Then 30mg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 2 | 3 | 2 | 2 | 3 |
| COMPLETED | 3 | 2 | 3 | 2 | 2 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period 3 - Second Intervention
| Stage | First 30mg, Then 90mg, Then 120mg, Then Placebo | First 30mg, Then 90mg, Then Placebo, Then 120mg | First 120mg, Then Placebo, Then 240mg, Then 90mg | First Placebo, Then 30mg, Then 90mg, Then 120mg | First 90mg, Then Placebo, Then 120mg, Then 240mg | First Placebo, Then 240mg, Then 90mg, Then 30mg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 2 | 3 | 2 | 2 | 3 |
| COMPLETED | 3 | 2 | 3 | 2 | 2 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Period 4 - Second Washout Period
| Stage | First 30mg, Then 90mg, Then 120mg, Then Placebo | First 30mg, Then 90mg, Then Placebo, Then 120mg | First 120mg, Then Placebo, Then 240mg, Then 90mg | First Placebo, Then 30mg, Then 90mg, Then 120mg | First 90mg, Then Placebo, Then 120mg, Then 240mg | First Placebo, Then 240mg, Then 90mg, Then 30mg |
|---|---|---|---|---|---|---|
| STARTED | 3 | 2 | 3 | 2 | 2 | 3 |
| COMPLETED | 3 | 2 | 3 | 2 | 2 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Efficacy Analysis Set (EAS). From the safety analysis set with 27 patients, the EAS excludes 2 patients; 1 due to a positive drug of abuse screen and 1 due to poor quality of the impedance/pH tracings during all 4 study periods. Additionally, 3 patients were partly excluded from the EAS due to poor quality of the tracings during 1 study period.
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.
| Characteristic | Unit | Entire Study Population |
|---|---|---|
| Participants analysed | 27 | |
| Age Continuous | Years | 43.3 (18 to 68) |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Total Number of Reflux Episodes During 24 Hours, measured over Measured during 24 hours at 4 different visits with a 7-28 days interval between.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Episodes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the total number of reflux episodes during 24 hours. The registry defines an episode using impedance: it starts when impedance drops below 50% of baseline and ends when impedance recovers above 50% of baseline. Measurements were made by ambulatory impedance-pH recording during 24 hours at four visits, with a 7-28 days interval between visits.
This endpoint counts recorded reflux events rather than relying only on a report of symptoms. Impedance-pH monitoring can characterize reflux episodes while also distinguishing episodes by acidity, which aligns with the listed secondary outcomes for acid, weakly acidic, and weakly alkaline reflux. As a general statistical point, an objective event count can describe a physiologic feature of interest, but it is not by itself a measure of how a participant feels or functions.
The registry reports the primary endpoint as a geometric mean with a 95% confidence interval. These summaries describe the endpoint estimates and their statistical uncertainty; they do not show the range of individual participant counts. The record does not explain why the geometric mean was selected or specify the model used to account for the crossover structure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-endpoint estimates are geometric means of 59.4 for AZD3355 30 mg, 50.7 for AZD3355 90 mg, 44.3 for AZD3355 120 mg, 38.0 for AZD3355 240 mg, and 80.5 for placebo. The corresponding 95% confidence intervals are 49.1 to 71.8, 41.8 to 61.4, 36.9 to 53.2, 31.4 to 46.0, and 67.5 to 96.1, respectively. The listed estimates are lower at each successively higher AZD3355 dose, while the placebo estimate is higher than each active-dose estimate. This is a description of the posted summaries, not a reported test of a dose trend or of treatment differences.
The number of observations contributing to the treatment-specific summaries varies: 18 for AZD3355 30 mg, 17 for 90 mg, 20 for 120 mg, 18 for 240 mg, and 24 for placebo. In a crossover study, these treatment-specific counts should not automatically be read as separate groups of participants. The registry does not explain the treatment-level count differences or state how incomplete measurements were handled.
A confidence interval indicates uncertainty around an estimate under the assumptions of the analysis; it is not an interval containing a fixed proportion of individual participants’ results. The intervals allow readers to assess the precision of each treatment-specific geometric mean, but they do not replace a direct comparison. The registry reports no analyses for the primary outcome and no p-values, treatment-effect estimates, or confidence intervals for between-treatment contrasts. Consequently, the posted values alone do not establish statistical significance or quantify a treatment contrast.
The overall enrollment was 27, while the primary endpoint summaries use the EAS. The registry says that the EAS excludes 2 patients from a safety analysis set of 27, with one exclusion due to a positive drug of abuse screen and one due to poor quality of impedance/pH tracings during all 4 study periods. It also says that 3 patients were partly excluded from the EAS because of poor—further detail is not reported in the registry record. These analysis-population details matter when considering why the treatment-specific counts differ from overall enrollment.
The registry lists three secondary reflux outcomes and reports four outcome measures, but it does not post analysis results for the secondary outcomes. The findings therefore concern only the reported primary-endpoint summaries. They cannot establish whether patterns were similar for acid, weakly acidic, or weakly alkaline episodes.
9. Statistical Methods Explained
The registry reports treatment-specific geometric means and 95% confidence intervals for the primary endpoint. It does not report the statistical model, the method used to estimate those summaries, or a formal comparison among the treatments. The distinction between a descriptive summary and an inferential comparison is important: a set of estimates can be inspected for patterns, but a formal analysis is needed to quantify uncertainty in differences or a dose-response relationship.
What does a geometric mean describe?
As a general statistical explanation, a geometric mean summarizes positive measurements on a multiplicative scale. It is commonly obtained by transforming values to the logarithmic scale, averaging on that scale, and transforming the result back. It is not the same summary as an arithmetic average. The registry identifies the primary endpoint statistic as a geometric mean but does not state the estimation method or the distributional assumptions used.
The reported values are treatment-specific summaries of reflux-episode counts. They do not show how counts varied from participant to participant, and they are not individual predictions. The registry also does not say whether any transformation, model adjustment, or other handling of the count distribution was used in producing them. Such details are not reported in the registry record.
How should the confidence intervals be read?
As a general explanation, a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure and its assumptions. The 95% intervals attached to the geometric means describe the precision of those individual summaries. They are not ranges that contain 95% of participants’ values, and they are not automatically confidence intervals for differences between treatments.
To evaluate a contrast, an analysis would ordinarily estimate the difference or another defined comparison and its uncertainty, using a method suited to the study design and endpoint. No such contrast estimates or tests are reported for this primary outcome. Comparing the positions or overlap of separate confidence intervals is not a substitute for a reported comparison test, especially when the study uses a crossover design.
Why does crossover structure matter?
As a general statistical explanation, a crossover study measures participants under more than one treatment condition. A suitable analysis can use within-participant information, which may account for stable differences between people. It may also need to consider features such as treatment period, treatment order, and possible carryover from an earlier period. Those considerations depend on the design and analysis plan. The registry identifies a crossover model and visits separated by a 7-28 days interval, but does not report treatment sequences or how the analysis addressed period, order, or carryover effects.
The treatment-specific counts are not identical: 18, 17, 20, 18, and 24 are listed for the four dose summaries and placebo. In a crossover setting, these numbers can represent available observations by treatment rather than independent treatment groups. The record does not clarify their precise interpretation, explain the differences, or describe how partial records entered the analysis.
What is not available for inference?
The registry gives no primary-outcome analysis results, no p-values, and no direct estimates of contrasts. It also does not report an analysis plan, a model specification, an approach to multiplicity, or a sample-size justification. These omissions limit what can be concluded from the endpoint summaries. The posted values can be described as a pattern across treatment labels, but the record does not document a formal test of that pattern.
As a general point, over-dispersion occurs when count outcomes vary more than a chosen statistical model expects. If present, it can affect uncertainty estimates and the reliability of tests unless handled appropriately. The registry does not report whether over-dispersion was assessed or how the count endpoint was modelled; no conclusion about its presence or handling can be drawn from the reported summaries alone.
The registry also identifies three secondary outcomes, but does not report their analysis results. A complete statistical interpretation would need to know which hypotheses were prespecified, which analyses were performed, how repeated measurements and missing observations were handled, and whether any adjustment was planned for multiple comparisons. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint and three secondary outcomes: number of acid reflux episodes, number of weakly acidic reflux episodes, and number of weakly alkaline reflux episodes. It reports four outcome measures, but no analyses are posted. The record does not report which comparisons or hypotheses were prespecified, whether the dose levels were to be tested individually or as a trend, or whether any multiplicity adjustment was planned. It is therefore not possible to determine how the risk of false-positive findings across multiple analyses was managed.
The primary endpoint population is described as the EAS. The registry says this set was drawn from the safety analysis set of 27 patients and excluded 2 patients: one because of a positive drug of abuse screen and one because impedance/pH tracings were of poor quality during all 4 study periods. It additionally states that 3 patients were partly excluded from the EAS due to poor—further detail is not reported in the registry record. The explanation of partial exclusions is incomplete.
The treatment-specific endpoint counts are 18, 17, 20, 18, and 24. The record does not explain the reasons for these differing counts, identify the exact observation-level rules for inclusion, or report imputation or other missing-data methods. It does not describe whether analyses used all available observations or how incomplete crossover records were treated.
These missing details make it difficult to assess the consequences of exclusions and incomplete measurements. No missing-data assumptions, sensitivity analyses, or analysis-population comparison results are reported in the registry record. The descriptive endpoint estimates should therefore be interpreted in light of the stated EAS exclusions and the lack of further information about partial exclusions and missing data.
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 |
|---|---|---|---|
| AZD3355 30 mg | 0 | 19 | 0.0% |
| AZD3355 90 mg | 0 | 21 | 0.0% |
| AZD3355 120 mg | 0 | 21 | 0.0% |
| AZD3355 240 mg | 1 | 20 | 5.0% |
| Placebo | 0 | 26 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AZD3355 30 mg | 0 of 19 |
| AZD3355 90 mg | 1 of 21 |
| AZD3355 120 mg | 0 of 21 |
| AZD3355 240 mg | 3 of 20 |
| Placebo | 2 of 26 |
Most frequent serious adverse event terms
| Event term | Organ system | AZD3355 30 mg | AZD3355 90 mg | AZD3355 120 mg | AZD3355 240 mg | Placebo |
|---|---|---|---|---|---|---|
| Blood creatine phosphokinase increased | Investigations | 0 of 19 | 0 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
| Alanine Aminotransferase Increased | Investigations | 0 of 19 | 0 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
| Aspartate aminotransferase increased | Investigations | 0 of 19 | 0 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AZD3355 30 mg | AZD3355 90 mg | AZD3355 120 mg | AZD3355 240 mg | Placebo |
|---|---|---|---|---|---|---|
| Gastroenteritisviral | Infections and infestations | 0 of 19 | 0 of 21 | 0 of 21 | 0 of 20 | 2 of 26 |
| Nausea | Gastrointestinal disorders | 0 of 19 | 1 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
| Sinusitis | Infections and infestations | 0 of 19 | 0 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
| Vomiting | Gastrointestinal disorders | 0 of 19 | 0 of 21 | 0 of 21 | 1 of 20 | 0 of 26 |
Serious events with the highest arm-level rate: blood creatine phosphokinase increased (5.0%), alanine aminotransferase increased (5.0%), aspartate aminotransferase increased (5.0%).
The registry lists serious adverse events by treatment and gives the number at risk and the number affected. For AZD3355 30 mg, 0 of 19 were affected; for AZD3355 90 mg, 0 of 21; for AZD3355 120 mg, 0 of 21; for AZD3355 240 mg, 1 of 20; and for placebo, 0 of 26. These are the recorded group counts, not a statistical comparison of safety between treatments.
The record also lists other adverse events: 0 of 19 for AZD3355 30 mg, 1 of 21 for 90 mg, 0 of 21 for 120 mg, 3 of 20 for 240 mg, and 2 of 26 for placebo. These counts should be read separately from the serious adverse event counts. The registry does not give event-level details alongside these group totals or explain how adverse events were attributed across crossover periods.
Deaths are not reported in the registry record. The leading serious adverse event terms are listed as Blood creatine phosphokinase increased, Alanine Aminotransferase Increased, and Aspartate aminotransferase increased, each at 5.0%. The record does not give further context for these term-level percentages here, so they should not be interpreted as treatment-specific rates. Small group counts and the absence of a reported comparative safety analysis limit conclusions from these figures.
12. What the Result Does, and Does Not, Mean
The posted primary-endpoint summaries describe the geometric mean number of reflux episodes during 24 hours for each listed treatment. The estimates are 59.4 for AZD3355 30 mg, 50.7 for 90 mg, 44.3 for 120 mg, 38.0 for 240 mg, and 80.5 for placebo. They show a descending sequence across the listed active doses and a higher estimate for placebo than for each active-dose summary. Their 95% confidence intervals communicate uncertainty about the treatment-specific estimates.
That pattern does not, by itself, establish that AZD3355 caused a reduction in reflux episodes or that the dose-related pattern is statistically reliable. The registry does not report a treatment contrast, a formal dose-response test, a p-value, or a model accounting for the crossover design. The estimates are not a substitute for those analyses, and the record does not provide the information needed to assess their assumptions.
The endpoint concerns recorded reflux events, not the full experience of GERD or symptom relief. The study population is described as having GERD and a partial response to PPI treatment, but the listed primary endpoint is an impedance-pH count. The registry’s secondary outcomes distinguish acid, weakly acidic, and weakly alkaline episodes, yet their analysis results are not reported.
The registry reports an EAS drawn from a safety analysis set of 27, with exclusions and partial exclusions described incompletely. Treatment-specific counts vary, and no missing-data method or sensitivity analysis is reported. The available summaries therefore need to be read as estimates from the analysis population and observations documented in the record, not as a complete account of every enrolled participant’s response.
In short, the record supplies descriptive endpoint estimates and uncertainty intervals, along with limited safety counts. It does not establish a statistically tested treatment effect, a clinically meaningful effect, or a complete account of outcomes and analysis choices. Those distinctions prevent the numerical pattern from being treated as a definitive efficacy conclusion.
13. Why This Trial Matters Statistically
This study is statistically interesting because its crossover structure and dose-ranging question call for more than a simple comparison of separate group averages. In a crossover design, participants may contribute observations under multiple treatments. A suitable analysis can use within-participant information, but interpretation also depends on how treatment order and period are handled. The registry identifies the design but does not report the analysis details needed to assess those features.
The primary summaries show a dose-ordered pattern across the four AZD3355 doses, with geometric means of 59.4, 50.7, 44.3, and 38.0, and a placebo estimate of 80.5. This makes the distinction between pattern description and hypothesis testing especially important. A dose-response claim requires an appropriate analysis and uncertainty assessment; neither is reported for the primary outcome. The posted treatment-specific confidence intervals do not provide the missing contrast estimates.
The record also illustrates why analysis populations matter. Although enrollment is 27, the primary outcome uses the EAS, with exclusions and partial exclusions noted, and treatment-specific counts differ. Without fuller explanations of incomplete observations and the analysis method, readers cannot fully assess how those decisions affected precision or comparability.
Finally, statistical interpretation extends beyond the primary endpoint. Three secondary reflux outcomes are listed, but no analyses are posted, and multiplicity handling is not reported. The record thus supports a focused reading of descriptive summaries, while leaving central questions about formal inference, missing data, and analysis strategy unresolved.
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 registry record does not report the statistical model used for the primary endpoint, the procedure used to estimate the geometric means, or the method used to account for the crossover design. Treatment sequences and the handling of period, order, and possible carryover effects are not reported. These omissions make it difficult to evaluate whether the estimates and their uncertainty reflect the design appropriately.
The analysis population is described only in part. The EAS excludes 2 patients from the safety analysis set of 27 for stated reasons, and 3 patients were partly excluded because of poor—further detail is not reported in the registry record. The record does not explain the treatment-specific sample counts, describe missing-data assumptions, or report sensitivity analyses. The posted endpoint summaries therefore cannot establish how incomplete or excluded observations influenced the results.
No formal primary-endpoint analyses are posted, and no between-treatment effect estimates, p-values, or dose-response test results are reported. The record also does not describe a sample-size justification, planned multiplicity handling, or an analysis plan. Although three secondary outcomes are listed, their analysis results are absent. These gaps limit inferential interpretation and prevent assessment of whether any unreported analyses were prespecified.
The endpoint is a 24-hour count from impedance-pH recording. It describes recorded reflux episodes but does not, by itself, capture symptom burden or other patient experiences. The record does not provide enough information to assess the relationship between the endpoint and symptoms in this study. Safety counts are also limited: the record does not provide deaths, and term-level serious adverse event percentages lack treatment-specific context. These limitations are specific to the information documented for this trial and do not establish that unreported procedures or analyses were or were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Estimate Effect of 4 Different Doses of AZD3355 on Reflux Episodes, Which Patients With Gastroesophageal Reflux Disease (GERD) May Experience — NCT01043185.
- Registry record last updated 2011-06-14; status last verified 2011-05.
- Results first posted 2011-06-14.
- 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
NCT01043185 is a completed, randomized, triple-masked, placebo-controlled Phase IIA crossover study sponsored by AstraZeneca. It enrolled 27 patients with GERD and a partial response to PPI treatment and evaluated AZD3355 at 30 mg, 90 mg, 120 mg, and 240 mg against placebo.
The primary endpoint was total reflux episodes during 24 hours, measured by ambulatory impedance-pH recording. The registry reports treatment-specific geometric means and 95% confidence intervals, with endpoint counts varying across treatments. It describes EAS exclusions but gives incomplete detail about partial exclusions. Three secondary reflux outcomes are listed, but no analyses are posted. The registry does not report formal treatment comparisons, the statistical model, multiplicity handling, or missing-data methods. Safety counts are listed by treatment, while deaths are not reported in the registry record.