Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults (NCT02254486), a randomized phase 3 study. The primary outcome is Number of Patients With Successful Bowel Cleansing (Overall Colon).

2. Clinical Question

The endpoint classifies cleansing as successful or unsuccessful using grades from the Harefield Cleansing Scale. The primary assessment covered the overall colon during the two days from first dosing to colonoscopy. A blinded central reader assessed segmental scores and derived a final grade. Grades A and B counted as successful, while grades C and D counted as unsuccessful.

The central reader was described as an experienced and trained colonoscopist. The registry identifies the trial as single-masked, but does not report which trial participants or personnel were masked. Nor does the record report the threshold that would define an acceptable loss of efficacy for the non-inferiority comparison. These details matter because a non-inferiority conclusion depends on both the observed comparison and a prespecified margin. The endpoint definition alone cannot determine whether the study met its primary objective.

3. Trial Design

This was a multicenter, randomized, parallel-group Phase III study sponsored by Norgine. The registry lists the study as completed. The recorded study start was 2014-09, and the primary completion was 2015-06. The registry lists enrollment as 621. The brief summary separately says that approximately 540 patients would be randomized, with the aim of achieving a minimum of 245 patients in each of the two groups. Those planning statements should not be treated as the observed allocation: the record does not give the number randomized to each arm in the information available for this analysis.

Participants were assigned to NER1006 or Trisulfate Solution, with both groups following a 2-day evening/morning split-dosing regimen that began in the evening before colonoscopy. A parallel-group design assigns participants to one treatment group for comparison with another group. Random allocation is intended to reduce systematic differences between groups, although the method used to generate or conceal assignments is not reported in the registry record.

The study is described as single-masked. The registry does not specify who was masked, so it is not possible to determine from the record whether masking applied to participants, clinical staff, outcome assessors, or another group. Separately, the primary outcome description says that a blinded central reader assessed the cleansing scores. This identifies masking for that assessment but does not fill in the broader masking details.

The primary outcome was the number of participants with successful overall-colon cleansing, assessed over two days from first dosing to colonoscopy. The registry also lists adenoma detection rate and polyp detection rate, each for the ascending and overall colon. It records six outcome measures and six analyses, but the available information does not provide a complete account of their statistical specifications or results.

The study’s stated purpose was to compare cleansing efficacy, safety and tolerability. It used a non-inferiority design for the overall success comparison. The registry record does not report the non-inferiority margin, the planned statistical model, or the full analysis plan. These omissions limit assessment of how the planned design was implemented and how its primary objective should be judged.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The overall number of participants analyzed was based on the mFAS. This included all randomized patients, except any patient who (i) was randomized but subsequently failed to meet entry criteria and (ii) in whom it was confirmed (from their patient diary) that the same patient did not receive any study drug.

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 number of participants for analysis, 245 per arm, was based on assumed overall cleansing success rates of 90% for both Trisulfate Solution (TS) and NER1006, a non-inferiority (NI) margin of 10%, and at least 90% power to demonstrate NI. The overall number of participants analyzed was based on the modified full analysis set (mFAS).

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Successful Bowel Cleansing (Overall Colon), measured over Two days (from day of first dosing to day of colonoscopy).

The primary endpoint counts participants whose overall bowel cleansing was classified as successful. A blinded central reader assessed segmental scores using the Harefield Cleansing Scale and derived a final grade. Grades A and B were classified as successful, meaning all mucosa could be visualised; grades C and D were classified as unsuccessful. The assessment timeframe was two days, from the day of first dosing to the day of colonoscopy.

This endpoint is used to represent whether the cleansing preparation achieved the visibility needed for examination of the colon. In this trial, success was defined by the scale’s grade categories rather than by a continuous measure. That makes the primary outcome binary: each participant contributes to the successful or unsuccessful category. The endpoint concerns cleansing quality, not adenoma or polyp detection itself; those detection rates are listed separately as secondary outcomes.

The registry says overall success was compared using a non-inferiority design. In general, non-inferiority testing asks whether the difference between treatments rules out a loss greater than a prespecified acceptable margin. The registry record does not report that margin or the primary comparison in a usable, single-result form. It therefore describes what was measured and the type of question planned, but does not support a conclusion about whether the non-inferiority criterion was met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary outcome is a binary participant-level measure. Each participant’s overall-colon cleansing assessment was classified as successful or unsuccessful using the final Harefield Cleansing Scale grade. Grades A and B were successful, and grades C and D were unsuccessful. General statistical explanation: a binary endpoint reduces a result to two possible categories for each participant. The comparison then concerns how often each category occurs in the groups, although the registry record does not provide a single primary comparison that can be interpreted.

The endpoint was assessed by a blinded central reader using segmental scores. Central assessment can provide a consistent basis for applying the scale across participants, while blinding can reduce the possibility that knowledge of treatment assignment influences the assessment. The registry describes the reader as blinded, experienced and trained. It does not report the reader procedures, scoring reliability, or whether any other trial roles were masked.

What does non-inferiority mean?

General statistical explanation: a non-inferiority design evaluates whether the results rule out a loss of effect larger than a prespecified margin that has been judged acceptable for the study question. The margin is essential to interpretation; the observed estimate alone is not enough. A confidence interval expresses the range of treatment differences compatible with the data under the statistical model. For non-inferiority, the interval is interpreted relative to the margin and the direction in which a loss would occur.

The registry states that the primary comparison used a non-inferiority design, but the margin, treatment contrast, statistical model and confidence interval are not reported in the registry record. The primary outcome is also not reduced to one comparison in the available information. As a result, neither the margin-based decision nor the precision of the primary estimate can be evaluated. No claim about meeting or failing the non-inferiority criterion follows from the design label alone.

What can be said about randomization and masking?

The study is described as randomized and parallel-group. In general, random assignment aims to make treatment groups comparable with respect to factors that could affect the outcome, including factors that are not measured. It does not guarantee exact balance in every sample. The record does not explain the sequence-generation method, allocation concealment, stratification, or the group assignment counts for the primary analysis.

The study is also described as single-masked, and the primary outcome assessment is described as blinded at the central-reader stage. The identity of the masked party or parties is not reported in the registry record. These descriptions should not be expanded into assumptions about participant or clinical-staff masking.

What do the sample-size assumptions represent?

General statistical explanation: sample-size planning estimates how many participants may be needed to detect a specified effect under stated assumptions. It is a planning exercise, not an observed result and not a measure of the probability that a completed study found an effect. The planning illustration associated with this analysis is described as using a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. It is explicitly not the trial’s own design calculation.

Those assumptions do not establish the trial’s original sample-size justification. The registry record does not report the trial’s own statistical sample-size rationale, and planning illustrations cannot substitute for that information. They also cannot establish observed power. No such interpretation should be attached to planning counts.

Why does dispersion matter for some outcomes?

General statistical explanation: for count outcomes, the variability may be greater than expected under a simple model that assumes the variance is tied closely to the mean. This is called over-dispersion. If it is ignored, uncertainty can be understated and tests or intervals can be poorly calibrated. This general issue is not a reported feature of the primary endpoint in this trial: the primary outcome is described as a count of participants classified into success categories, and no over-dispersion analysis is reported in the registry record.

What can be inferred from the posted statistical information?

The registry records six outcome measures and six analyses, but the available information does not describe the full analysis methods or provide a single primary comparison. It does not report the primary effect estimate, its confidence interval, or a p-value for an interpretable primary contrast. General statistical explanation: an estimate describes the size and direction of a comparison, while its interval conveys uncertainty under the analysis assumptions. A p-value addresses compatibility with a specified null hypothesis; it does not by itself establish clinical importance or non-inferiority. Because these primary results and the decision margin are absent, those interpretations cannot be made for this trial from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses. The listed secondary outcomes include adenoma detection rate and polyp detection rate for both the ascending and overall colon. The record does not report how the analyses were organized into primary, secondary, or exploratory families beyond identifying the primary cleansing outcome and listing those secondary outcomes.

When multiple outcomes or analyses are examined, the chance of a false-positive finding can increase if each is interpreted without accounting for the number and structure of the tests. General statistical explanation: multiplicity procedures can control that risk, or an analysis plan can define a hierarchy in which some outcomes are tested only after earlier criteria are met. The registry record does not report a multiplicity strategy, a testing hierarchy, or which results were intended to support confirmatory claims. No adjustment or absence of adjustment should be assumed.

The primary analysis population is described as the modified full analysis set. It included randomized patients, except for patients who were randomized but subsequently failed to meet entry criteria, and an additional exclusion criterion related to diary-confirmed nonreceipt of treatment. The registry description is truncated during that second criterion, so its complete wording and the full analysis-population definition are not reported in the registry record.

The record does not report how missing outcome data were handled, how many primary-outcome observations were missing, whether imputation was used, or whether sensitivity analyses were performed. These details are particularly relevant to interpretation of a non-inferiority study, because missing observations and analysis-population choices can affect the estimated treatment difference. The available description is not enough to assess those choices or their impact.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ileus (0.4%), gastrintestinal haemorrhage (0.4%).

The registry reports one participant with a serious adverse event in each group: 1 of 265 in the Trisulfate Solution 2-Day Split-Dosing group and 1 of 262 in the NER1006 2-Day Split-Dosing group. It lists 32 of 265 and 73 of 262 in the other adverse-event category, respectively. Deaths are recorded as zero in both groups. These counts should be read as the posted group summaries, not as a statistical comparison or evidence of a causal treatment effect.

The registry also lists Ileus and Gastrintestinal haemorrhage among the top serious terms, each at 0.4%. These term percentages are reported as written; the record excerpt does not provide further context about event counts by term, overlap, timing or relatedness. The serious-event counts and the other adverse-event counts are separate categories in the registry summary and should not be added together to create a new total.

General statistical explanation: adverse-event counts are descriptive unless a prespecified comparison and suitable uncertainty estimates are also reported. The registry record does not provide such a comparison for these figures. It also does not give the duration or completeness of safety follow-up in the information. The counts therefore describe what was recorded, but do not by themselves establish whether the groups differed in safety.

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

The record establishes that a randomized, parallel-group Phase III study compared NER1006 with Trisulfate Solution using a 2-day split-dosing regimen in adults requiring bowel cleansing before a procedure requiring a clean bowel. It defines successful overall cleansing through grades A and B of the Harefield Cleansing Scale, with grades C and D classified as unsuccessful. It also states that the primary comparison was designed as a non-inferiority assessment.

Those details explain the clinical and statistical question, but they do not answer it. The registry information available for this analysis does not give a single primary-outcome comparison, an effect estimate, a confidence interval, or the non-inferiority margin. Without those elements, it is not possible to determine whether the planned criterion was met, to quantify the observed difference, or to describe its precision. The completed status of the study does not change that limitation.

The record’s safety summary reports one participant with a serious adverse event in each group, other adverse-event counts of 32 and 73 in the respective groups, and zero deaths in either group. It also lists two serious-event terms at 0.4% each. These are registry summaries, not a complete account of safety, and they do not establish a treatment-related difference. No statistical comparison of these counts is reported in the information.

The record also does not provide enough detail to assess the full analysis population, missing-data handling, multiplicity procedures or the implementation of the non-inferiority analysis. Those limitations matter because a study’s conclusion depends not only on its endpoint definition, but also on the analysis plan, the observed data and the uncertainty around the treatment comparison.

Thus, the posted information supports a careful description of what the trial set out to test and some recorded safety counts. It does not support saying that either bowel-cleansing solution was superior, equivalent, non-inferior, or inferior on the primary endpoint. Such conclusions require the primary results and methodological details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry’s design description and its results need to be read separately. The record identifies a randomized Phase III study, a specific cleansing scale, a blinded central assessment and a non-inferiority objective. Those features clarify the question researchers intended to address. They do not, by themselves, show what the comparison found.

Non-inferiority studies are particularly dependent on transparent reporting of the margin and the treatment-effect interval. A statement that the study was designed for non-inferiority is not the same as evidence that non-inferiority was demonstrated. Without the margin and a usable primary estimate, readers cannot evaluate the decision rule or the precision of the result. This is a substantive interpretive limit, not merely a missing detail in presentation.

The registry also distinguishes the planned enrollment target from recorded enrollment. It lists enrollment as 621, while the brief summary describes a target of approximately 540 randomized participants and a minimum of 245 in each group. Keeping those figures distinct prevents a planning statement from being mistaken for the observed arm-specific analysis population.

Finally, the record exposes common reporting questions that matter in clinical trials: who was masked, how the analysis population was defined, how missing observations were handled, and how multiple outcomes were interpreted. The primary endpoint is clearly described, but the available analysis details do not resolve those questions. For biostatisticians and clinical researchers, the central lesson is that meaningful interpretation requires both a well-defined outcome and enough reported methods and results to connect that outcome to the study’s stated objective.

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 most important limitation for interpretation is that the registry describes the primary outcome and its non-inferiority purpose without reporting a single primary comparison that can be evaluated. The non-inferiority margin, effect estimate and confidence interval are not reported in the registry record. Consequently, the primary statistical conclusion and its precision cannot be assessed from the available information.

Details needed to understand trial implementation are also missing. The record does not specify the randomization procedure or allocation concealment, and it does not identify who was masked under the single-masked designation. Although the primary assessment is described as blinded central reading, further details about scoring procedures are not reported in the registry record.

The analysis population is only partly defined. The description identifies exclusions involving failure to meet entry criteria and diary-confirmed nonreceipt of treatment, but it is truncated during the latter criterion. The full modified full analysis set definition, arm-specific numbers in that analysis, and the number of participants with missing outcome data are not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported.

The record lists multiple outcomes and analyses but does not explain a multiplicity strategy or testing hierarchy. It does not report the trial’s own sample-size justification, interim analyses, or a complete statistical analysis plan. These omissions prevent assessment of whether the posted analyses match the intended confirmatory approach. Finally, the safety summary provides selected counts and terms without additional detail on timing, follow-up or relatedness. These limitations restrict interpretation; they should not be replaced with assumptions about the protocol or conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults — NCT02254486.
• Registry record last updated 2018-05-15; status last verified 2018-04.
• Results first posted 2017-05-23.
• 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.

18. Record Summary

The registry record describes NCT02254486, a completed, randomized, single-masked, parallel-group Phase III study sponsored by Norgine. It compared NER1006 with Trisulfate Solution using a 2-day split-dosing regimen in adults requiring bowel cleansing before a procedure that requires a clean bowel. Recorded enrollment was 621; the brief summary described a planned enrollment of approximately 540 randomized participants and a minimum of 245 in each group.

The primary endpoint was successful overall-colon cleansing, assessed over two days using the Harefield Cleansing Scale and a blinded central reader. The study’s stated primary comparison used a non-inferiority design. The registry lists adenoma and polyp detection rates for the ascending and overall colon as secondary outcomes.

The available record does not report the non-inferiority margin or a single interpretable primary-outcome comparison. It reports one participant with a serious adverse event in each group, other adverse-event counts of 32 and 73, and zero deaths in both groups. The posted information therefore describes the study question and selected safety counts, but does not establish the primary efficacy result.