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 Safety and Tolerability of Oral Polyethylene Glycol (PEG 3350) Solution in Participants With Constipation (MK-8114-003) (NCT01885104), a randomized phase 2 study. The primary outcome is Number of Participants With Inflammation of the Oral Mucosa.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01885104 |
| Phase | Phase 2 |
| Condition | Constipation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 65 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bayer |
| Results posted | Yes |
2. Clinical Question
Population
Participants with constipation were eligible for the study. The primary endpoint population was described as the Safety Population: participants who received at least one dose of PEG 3350 or placebo and had at least one postdose safety assessment. The registry record does not report further eligibility details or participant characteristics.
Intervention
Participants assigned to PEG 3350 received a 17 g dose of solution concentrate in a volume of approximately 30 mL once a day for 14 days. Bisacodyl laxative tablets were available as rescue medication if a participant had not had a bowel movement. The recorded rescue dose was 5.0 mg, with 1 to 3 tablets in a single daily dose.
Comparator
The comparator was a placebo solution concentrate. The placebo arm description specifies a 17 g dose in a volume of approximately 30 mL once a day for 14 days. Bisacodyl rescue tablets were also provided under the same stated condition. The registry record does not identify which participants, if any, used rescue medication.
Primary question
The study was intended to compare the safety and tolerability of oral PEG 3350 solution concentrate with placebo in participants with constipation. The primary outcome concerned the number of participants with inflammation of the oral mucosa, assessed at Visit 2 and Visit 3. Although the registry defines the assessment, it does not report the result by arm or an inferential comparison.
3. Trial Design
This completed Phase 2 study is recorded as randomized, single-masked, and parallel-group. Randomization means that assignment to study arms was intended to be determined by chance, while a parallel design means participants were assigned to one study arm rather than crossing between the two. The registry describes the study as single-masked but does not report who was masked. It also does not report the method used to generate the random assignments or how assignments were concealed.
The registry lists enrollment as 65. It identifies two arms: PEG 3350 and placebo. The arm descriptions specify daily oral solution concentrate for 14 days, with bisacodyl tablets available as rescue medication if a participant had not had a bowel movement. The record does not state how rescue medication use was incorporated into the endpoint analysis.
The recorded condition was constipation. The study's stated purpose was to compare the safety and tolerability of oral PEG 3350 solution concentrate with a placebo solution concentrate. The start is listed as 2013-04, primary completion as 2013-09, and status as completed. The sponsor is Bayer.
The registry identifies an oral-mucosa assessment as the primary outcome. It describes examinations at Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after treatment began. The outcome definition includes a four-level scale for inflammation. However, there are no reported primary outcome counts, arm-level outcome estimates, or analyses in the record. The number of participants analyzed for the primary endpoint, beyond the Safety Population definition, is 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.
Overall Study
| Stage | PEG 3350 | Placebo |
|---|---|---|
| STARTED | 31 | 34 |
| COMPLETED | 29 | 33 |
| NOT COMPLETED | 2 | 1 |
Reasons for not completing this period:
| Reason | PEG 3350 | Placebo |
|---|---|---|
| Withdrawal of Consent | 1 | 0 |
| Lost to Follow-up | 0 | 1 |
| Physician Decision | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population, which consisted of all participants who received at least 1 dose of PEG 3350 or placebo and had at least 1 postdose safety assessment.
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: Safety Population, which consisted of all participants who received at least 1 dose of PEG 3350 or placebo and had at least 1 postdose safety assessment.
| Characteristic | Unit | PEG 3350 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 31 | 34 | 65 | |
| Age, Continuous | Years | 44.5 (SD 13.87) | 48.0 (SD 15.17) | 46.4 (SD 14.56) |
| Sex: Female, Male: Female | Participants | 24 | 27 | 51 |
| Sex: Female, Male: Male | Participants | 7 | 7 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Inflammation of the Oral Mucosa, measured over Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days), up to 19 days after start of treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Particpants |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of participants with inflammation of the oral mucosa. Participants underwent a visual examination at Visit 2 and Visit 3. The registry describes a 0–3 Likert scale: 0 means no inflammation, 1 means mild inflammation, 2 means moderate inflammation, and 3 means severe inflammation. The descriptions distinguish these categories by the presence of erythema and whether erosion or ulceration was present.
An endpoint of this kind records a safety finding observed during examination, rather than a symptom reported by the participant or a measure of constipation severity. In general, examining the oral mucosa can be used to monitor a possible local finding during exposure to an orally ingested solution. The registry record does not give a rationale for selecting this endpoint or explain how observations at the two visits were combined into the participant-level count.
The title and outcome description indicate that the endpoint concerns participants with inflammation, but the record does not provide the number in either arm, the criteria used to classify a participant across visits, or an estimate of the difference between arms. Consequently, the endpoint definition can be described, but its observed results cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available registry information describes the study design, treatment schedules, endpoint definition, and selected safety counts. It does not provide a reported comparison for the primary endpoint. Although the oral-mucosa outcome is defined using examination findings at two visits, arm-specific results for that outcome are not reported in the registry record. There is therefore no posted estimate of how often the endpoint occurred in either arm and no reported statistical test or confidence interval for a treatment-group comparison.
For serious adverse events, the registry lists zero affected participants in both arms. The number at risk is listed as 31 for PEG 3350 and 34 for placebo. These entries describe the recorded serious-adverse-event counts over the available reporting period; they do not establish that no other safety events occurred. The registry separately lists other adverse-event counts: 11 affected participants among 31 at risk for PEG 3350, and 17 among 34 at risk for placebo. The specific terms and severity details for those other events are not included in the record.
These counts should be read descriptively. A difference in observed counts between randomized arms is not, by itself, evidence of a reliable treatment effect. Interpretation would require knowing the event definitions and observation periods, the analysis approach, and the precision of any estimated contrast. The registry does not report a statistical comparison for these counts or confidence intervals. No relative or absolute effect estimate is reported in the registry record.
The trial is described as randomized, which supports a design intended to make the groups comparable on average, but the record does not report the randomization procedure, masking details beyond the single-masked label, or baseline characteristics. Nor does it report the handling of missing assessments, rescue medication use, or protocol deviations in an analysis. These omissions limit assessment of how the reported counts relate to the intended comparisons.
The registry states that its primary outcome has several categories or time points and was not reduced to one comparison. That is consistent with caution about treating the endpoint definition as though it were a single reported result. The absence of a reported comparison is not evidence that the arms were equivalent, and it does not establish either benefit or harm. The posted information supports a description of the protocol and recorded counts, but not a conclusion about comparative tolerability from the primary endpoint.
9. Statistical Methods Explained
Statistical interpretation begins by separating what a trial planned to measure from what its registry record reports as a result. This record defines an oral-mucosa endpoint and gives adverse-event counts, but it does not report an arm-level primary endpoint analysis. The fact that an endpoint is specified does not supply the outcome values, an effect estimate, or its uncertainty.
What does randomization contribute?
In general, randomization assigns participants to groups by chance. It is intended to reduce systematic differences between groups at the start of a study, including differences in characteristics that may affect outcomes. Randomization does not guarantee that all characteristics will be balanced in a particular study, especially when group sizes are limited. Baseline characteristics and the precise randomization method are not reported in the registry record, so readers cannot assess balance or reconstruct the assignment process from this record.
The parallel design means the two groups received their assigned study regimen rather than switching between regimens. Single masking indicates that some aspect of treatment assignment was concealed, but the registry record does not say who was masked. That distinction matters in general because knowledge of assignment can affect how symptoms are reported, examinations are conducted, or events are attributed. The record does not describe steps used to limit those possibilities.
How should the endpoint scale be understood?
The oral-mucosa assessment uses ordered categories from no inflammation through severe inflammation. This is an ordinal scale: its categories have a rank, but the distances between adjacent categories are not necessarily equal. In general, a count of participants meeting a prespecified endpoint can be analyzed as a binary outcome, while a full ordinal score can be analyzed using methods that preserve the ordering. The registry gives a participant-count endpoint title and a scale definition, but it does not report the participant-level scoring rule, the distribution of scores, or an analysis method. It is therefore not possible to determine whether the analysis used the categories individually, a threshold, or another rule.
The assessments occurred at two visits, Visit 2 (Day 1) and Visit 3 (Day 17 ± 2 days). When an endpoint is assessed repeatedly, the analysis must define how repeated observations contribute to the final outcome. In general, an analysis might focus on a particular visit, the occurrence of a finding at any assessment, or change over time. Those approaches answer different questions. The rule used to form the reported participant count is not reported in the registry record, and the record does not report the resulting counts.
What do event counts show?
An adverse-event count describes how many participants in a group were recorded as affected under the registry's event classification. The serious-event entries list zero affected participants in each arm, while the other-event entries list 11 and 17 affected participants, respectively. These are descriptive counts, not estimates adjusted for differences in follow-up or event duration. The record does not report event-level details, person-time, or inferential tests for these entries. No additional rate or comparative estimate should be inferred from the counts alone.
For a binary outcome, a comparative analysis commonly reports an effect estimate, such as a difference in event proportions, along with a confidence interval. A confidence interval expresses the range of values reasonably compatible with the data under the analysis assumptions. Its width conveys precision: a wider interval indicates greater uncertainty. These are general statistical concepts. This registry record does not report a confidence interval or a primary endpoint effect estimate, so no precision statement about that comparison can be made.
Why does event variability matter?
For count outcomes, variation may exceed what a simple Poisson model expects, a property called over-dispersion. In general, over-dispersion can make standard errors from an overly simple model too small, which can make confidence intervals look more precise than warranted. Methods such as robust variance estimation or negative binomial models may be considered when appropriate. Nothing in the registry record indicates that the oral-mucosa endpoint or adverse-event counts were analyzed using a count model, and no model specification is reported. Because the primary endpoint is described as a participant count with several categories or time points, it should not automatically be treated as a simple count of independent events.
What can planning illustrations establish?
Sample-size calculations are planning exercises: they describe the sample size that would be needed under specified assumptions for a future or hypothetical study. They are not the same as observed power, which should not be used to reinterpret a completed study's results. The registry describes planning assumptions based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. Such calculations cannot replace a reported estimate and confidence interval, and they do not reveal the trial's original design rationale. The registry's own sample-size justification and statistical plan are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study assesses several outcomes, visits, treatment comparisons, or statistical tests. In general, the more opportunities there are to identify a result as statistically notable, the greater the chance of at least one apparent finding arising by chance if no adjustment is made. Approaches to multiplicity depend on which outcomes are confirmatory, the testing sequence, and the intended error control. The registry record does not report a multiplicity-adjustment plan.
The primary outcome is described across multiple inflammation categories and two visits. The registry explicitly indicates that this outcome was not reduced to one comparison. No statistical analyses are listed, and the record does not identify a primary contrast, provide a testing hierarchy, or state whether any adjustment was used. It is therefore not possible to evaluate multiplicity handling or interpret a primary hypothesis test from this record.
Missing data can also affect estimates. In general, interpretation depends on how many observations are missing, why they are missing, and how the analysis handles them. The record describes the Safety Population as participants who received at least one dose and had at least one postdose safety assessment. It does not report the number excluded from that population, missing oral-mucosa assessments, or any imputation or sensitivity-analysis method.
The population definition is useful for understanding whom the primary endpoint was intended to describe, but it is not a complete account of the analysis population for every outcome. The registry record does not report whether participants were analyzed according to randomized assignment for all comparisons, how rescue medication was handled, or whether other analysis populations were used. These details would be needed to assess the consequences of missing assessments and departures from the assigned regimen.
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 |
|---|---|---|---|
| PEG 3350 | 0 | 31 | 0.0% |
| Placebo | 0 | 34 | 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 |
|---|---|
| PEG 3350 | 11 of 31 |
| Placebo | 17 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PEG 3350 | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 6 of 31 | 5 of 34 |
| Abdominal pain | Gastrointestinal disorders | 4 of 31 | 6 of 34 |
| Nausea | Gastrointestinal disorders | 4 of 31 | 2 of 34 |
| Flatulence | Gastrointestinal disorders | 1 of 31 | 4 of 34 |
| Dizziness | Nervous system disorders | 2 of 31 | 2 of 34 |
| Abdominal distension | Gastrointestinal disorders | 0 of 31 | 3 of 34 |
| Diarrhoea | Gastrointestinal disorders | 2 of 31 | 1 of 34 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 31 | 2 of 34 |
| Abdominal discomfort | Gastrointestinal disorders | 0 of 31 | 2 of 34 |
| Haemorrhoids | Gastrointestinal disorders | 2 of 31 | 0 of 34 |
The serious adverse-event entries report zero affected participants in each arm. The registry lists 31 participants at risk in the PEG 3350 arm and 34 in the placebo arm for this category. These figures indicate what the registry records for serious adverse events; they do not establish that every possible adverse effect was absent or that the treatments have equivalent safety.
The record separately lists other adverse-event counts: 11 affected participants among 31 at risk in the PEG 3350 arm and 17 among 34 at risk in the placebo arm. The registry does not provide the specific event terms, timing, severity, or relationship to treatment for these other events in the information recorded. It also does not report a formal comparison or uncertainty interval for the counts.
In general, adverse-event counts are descriptive and depend on how events were defined, collected, and followed. A comparison of counts alone does not account for differences in event duration, repeated events, or follow-up time. The registry does not report those details. The serious-event entries should therefore be read as recorded counts, not as proof of absence of risk or as a stand-alone comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized, single-masked, parallel-group Phase 2 study of oral PEG 3350 solution concentrate versus placebo in participants with constipation. It specifies a 14-day daily dosing regimen and a visual oral-mucosa assessment at two visits. The primary outcome was defined as the number of participants with oral-mucosa inflammation, using a scale that distinguishes no, mild, moderate, and severe inflammation.
The record does not report the primary endpoint results by arm, an estimated treatment-group contrast, a confidence interval, or a test of the primary comparison. It therefore does not establish how the groups differed on oral-mucosa inflammation, nor how precisely any difference could be estimated. The absence of a reported comparison is not evidence that the groups had the same results.
The serious adverse-event counts are recorded as zero affected participants in both arms. Other adverse-event counts are also reported, but the registry does not provide event details or an inferential comparison for them. These descriptive entries can inform what was recorded, but they do not prove that an intervention is safe or unsafe, and they are not sufficient to establish comparative tolerability.
In general, a treatment comparison is most informative when an effect estimate is paired with its uncertainty, the analysis population and endpoint rules are clear, and the handling of missing data and multiple outcomes is described. Those elements are not reported for the primary comparison in this registry record. Accordingly, the record supports a limited description of the trial's design and selected safety counts, not a conclusion about whether PEG 3350 differs from placebo on the primary endpoint or overall safety.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical-trial interpretation: a registry can define an outcome and report some safety counts without providing the analysis needed to compare treatment groups. The oral-mucosa endpoint is described in operational terms, including the examination visits and an ordered severity scale. That information helps clarify what investigators intended to assess, but it does not substitute for observed outcome results.
The study also makes clear why the unit of analysis matters. The primary endpoint is framed as a number of participants with inflammation, while the underlying examination uses several ordered categories and occurs at two visits. In general, analysts must state how category scores and repeated assessments become a participant-level outcome. Without that rule and the resulting arm-level data, readers cannot reproduce or evaluate a treatment contrast.
The safety entries offer another statistical lesson: counts should not be mistaken for rates, adjusted comparisons, or evidence of equivalence. The registry reports serious and other adverse-event counts, but it does not report the event details, statistical uncertainty, or analysis methods needed for broader conclusions. A zero recorded serious-event count is a description of the observed record, not a guarantee about risk.
Finally, a study's size and design labels alone cannot resolve uncertainty about its findings. Randomization is a useful design feature, but interpretation also depends on allocation methods, outcome reporting, missingness, analysis populations, and prespecified statistical procedures. Several of those details are not reported in the registry record. This makes transparent reporting of estimates and analysis choices essential for statistical evaluation.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this trial is that the registry defines the primary oral-mucosa endpoint but does not report the endpoint results by treatment arm. It also gives no effect estimate, confidence interval, or statistical test. The clinical question can therefore be described, but the primary comparison cannot be evaluated from the record.
The endpoint description does not specify how the two visit assessments were combined to classify a participant as having inflammation. It does not report whether the analysis used a threshold, the highest score, a particular visit, or another rule. No distribution of scores is reported. Without these details, the endpoint's participant-level derivation cannot be independently assessed.
The registry identifies the trial as single-masked but does not state who was masked or describe the masking procedures. It does not report the randomization method, allocation concealment, baseline characteristics, or protocol deviations. These omissions limit assessment of possible group differences and conduct of the study.
For the other adverse-event counts, event terms and severity details are not reported in the record. The observation period and handling of repeated events are also not described. The record does not explain how rescue medication use was analyzed, nor does it report missing outcome assessments or the methods used to handle missing data.
Finally, the registry does not report the statistical analysis plan, a multiplicity strategy, or the rationale for the trial's planned size. It indicates that the primary outcome has several categories or time points and was not reduced to one comparison. These limitations mean that the posted information is insufficient for a detailed assessment of the treatment effect, its precision, or the robustness of the analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Tolerability of Oral Polyethylene Glycol (PEG 3350) Solution in Participants With Constipation (MK-8114-003) — NCT01885104.
- Registry record last updated 2015-03-11; status last verified 2015-02.
- Results first posted 2014-09-25.
- 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
This completed Phase 2 study was randomized, single-masked, and parallel-group. It compared daily oral PEG 3350 solution concentrate with placebo for 14 days in participants with constipation. Bisacodyl tablets were available as rescue medication if a participant had not had a bowel movement.
The primary endpoint was the number of participants with oral-mucosa inflammation, assessed visually at Visit 2 and Visit 3 using a 0–3 scale. The registry does not report the primary outcome results or a comparison between arms. It records zero participants with serious adverse events in each arm and lists other adverse-event counts of 11 among 31 at risk for PEG 3350 and 17 among 34 at risk for placebo. Event details and inferential safety comparisons are not reported in the registry record.