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 Rimeporide in Patients With Duchenne Muscular Dystrophy (NCT02710591), a registered phase 1 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02710591 |
| Phase | Phase 1 |
| Condition | Muscular Dystrophy, Duchenne |
| Allocation | Not Stated |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | EspeRare Foundation |
| Results posted | Yes |
2. Clinical Question
Population
Patients aged 6 to 14 years with Duchenne muscular dystrophy. The registry describes the safety population as all patients who received at least one dose of study drug; the endpoint observations are reported for that population.
Intervention
Multiple oral doses of rimeporide, administered three times a day for 4 weeks. The planned dose range was 50 to 300 mg across 4 ascending dose levels studied sequentially. Each patient was to participate in only one dose cohort.
Comparator
No control group or randomized comparison is reported. The study proceeded through sequential cohorts, so comparisons between cohorts are not like-for-like comparisons against a control group.
Primary question
The primary endpoint counts participants with adverse events, including treatment-emergent events, serious events, events considered related to study drug, and events leading to withdrawal or death. The question is descriptive: what adverse-event counts were recorded during follow-up, which extended up to 6 weeks from first administration?
This was a safety and tolerability study, not a trial designed in the registry record as a randomized test of clinical benefit. Its open-label design means treatment assignment was not masked. The posted endpoint is based on whether a participant experienced at least one event in each specified category; it is not a count of every event episode. The registry record does not report a control-group comparison or an adjusted estimate of treatment effect. Consequently, the findings are best read as observations within sequential dose cohorts. They can describe the adverse events recorded in this study, but cannot by themselves establish whether an event was caused by rimeporide or how outcomes would compare with an untreated group.
3. Trial Design
The registry record describes a phase Ib, open-label study of rimeporide in patients with Duchenne muscular dystrophy. The model is sequential: four ascending dose levels were studied in ascending order, and each patient was to take part in only one cohort. Oral doses ranging from 50 to 300 mg were administered three times a day for a total of 4 weeks. The record describes capsules of 25 mg or 50 mg. It does not give cohort-specific dose amounts in the outcome information.
Enrollment was 20. The record lists four cohorts, with 5 participants at risk in each cohort for the reported adverse-event counts. The study began in 2016-03, had primary completion in 2017-12, and is marked completed. It was sponsored by EspeRare Foundation. Masking is listed as none, and allocation is not stated. The record does not report a randomized control group. The sequential cohorts therefore should not be interpreted as treatment and control arms or as directly comparable groups in a randomized trial.
The primary endpoint was the number of participants with adverse events, assessed up to 6 weeks from first administration. Safety observations were defined for all patients who received at least one dose of study drug. The registry describes several event categories, including treatment-emergent adverse events, events considered related to study drug, serious events, events leading to withdrawal, and events leading to death. The posted cohort counts provide limited descriptive information; the registry record does not report an inferential analysis or a statistical plan for comparing cohorts.
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: Screening details: Screening was carried out within 4 week prior to first administration of Rimeporide (SD1) to enable confirmation of patient eligibility and following the signature of the Informed Consent Form.
Overall Study
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|
| STARTED | 5 | 5 | 5 | 5 |
| COMPLETED | 5 | 5 | 5 | 5 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Observations are given for the safety population (all patients who received at least one dose of 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: Safety population (all patients receiving at least one dose of Rimeporide)
| Characteristic | Unit | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 5 | 5 | 5 | 5 | 20 | |
| Age, Categorical: <=18 years | Participants | 5 | 5 | 5 | 5 | 20 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 8.4 (SD 1.7) | 8.2 (SD 1.5) | 8.8 (SD 1.6) | 9.2 (SD 0.4) | 8.7 (SD 1.3) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 5 | 5 | 5 | 5 | 20 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 | 5 | 5 | 5 | 20 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United Kingdom | participants | 0 | 1 | 3 | 1 | 5 |
| Region of Enrollment: Italy | participants | 0 | 1 | 2 | 3 | 6 |
| Region of Enrollment: France | participants | 5 | 0 | 0 | 1 | 6 |
| Region of Enrollment: Spain | participants | 0 | 3 | 0 | 0 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over up to 6 weeks from first administration.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with adverse events during follow-up of up to 6 weeks from first administration. The registry describes categorical summaries for participants with at least one event in several categories: treatment-emergent adverse events, events considered related to study drug, serious events, serious events considered related to study drug, events leading to withdrawal, related events leading to withdrawal, serious events leading to withdrawal, and events leading to death.
This endpoint is appropriate to the study’s stated safety and tolerability focus because it records whether participants experienced events that may warrant safety attention. A participant with multiple events within a category is counted as a participant with an event, rather than contributing a separate participant count for each episode. This distinction matters: the measure does not show the total number of event episodes, their duration, or their severity beyond the categories specified in the registry. It also does not, by itself, establish that an event was caused by the study drug. The registry record separates treatment-emergent events from events classified as related, but cohort-specific counts for every listed category are not reported in the posted results. The endpoint therefore gives a broad safety description, not a causal estimate of harm.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted adverse-event counts are descriptive and should be read by cohort. For serious adverse events, the registry reports 0 participants in Cohort 1, 0 in Cohort 2, 1 in Cohort 3, and 0 in Cohort 4. Each cohort had 5 participants at risk for this endpoint. The record reports 0 deaths in each cohort. For the other adverse-event count, it reports 2 participants in Cohort 1, 1 in Cohort 2, 5 in Cohort 3, and 4 in Cohort 4, with 5 at risk in each cohort. These are counts of participants affected, not event totals.
The pattern differs across the sequential cohorts, but the study is not reported as a randomized comparison. Cohorts were enrolled in ascending dose order, and the record does not report a control group. Differences in counts across cohorts therefore cannot be attributed to dose alone. The record does not report a statistical comparison, confidence intervals, or an adjusted analysis. The counts should not be treated as evidence of a trend or as precise estimates of what would occur in a broader population.
Seriousness, treatment-emergence, and relatedness are separate classifications. The endpoint description names each category, but the posted counts listed by cohort do not provide separate figures for all of them. In particular, a serious event count is not automatically a count of events considered related to study drug. Attribution requires the relevant classification, and it cannot be inferred from the occurrence of an event during the study.
The registry lists Diarrhoea and Vomitting among the serious adverse-event terms, each at 20.0%. Those term figures do not identify a cohort in the information, so they should not be assigned to a particular dose level. The record also does not provide event narratives, timing by participant, or a detailed account of repeated events. Thus, the posted information supports a limited description of the recorded safety outcomes, rather than a definitive comparison of risks across doses or a causal conclusion about rimeporide.
Small cohort counts are inherently imprecise: a change in the experience of a participant can materially alter a cohort’s observed count. This is a general statistical consideration, not an additional result from this study. Without reported uncertainty intervals or a comparison analysis, the apparent differences among cohorts should be interpreted cautiously. The absence of recorded deaths in the cohorts is a statement about the reported study observations, not proof that the risk of death is absent.
9. Statistical Methods Explained
What does a participant count measure?
The primary endpoint is a count of participants with at least one event in a defined category. This is different from counting all adverse-event episodes. If a participant experiences more than one episode, a participant-based summary does not necessarily increase by the same amount as an episode-based summary. The endpoint is useful for describing how many participants were affected, but it does not convey the total event burden, recurrence, duration, or clinical course. The registry record does not report those details in the posted cohort counts.
The categories also answer different questions. A treatment-emergent adverse event is classified by its occurrence during the relevant treatment period, whereas a related adverse event reflects an assessment of its relationship to study drug. A serious event is categorized by seriousness, which is distinct from whether it is considered related. A withdrawal or death category adds an outcome associated with the event. These classifications should not be treated as interchangeable. The registry lists them as separate selections for reporting, but the available cohort figures do not give all of those category-specific counts.
Why is the cohort structure important?
The study is described as sequential, with ascending dose levels studied in order. In a randomized controlled comparison, random assignment is intended to make groups comparable on average, subject to chance. That design feature is not reported. In a sequential study, cohort membership is linked to the order in which dose levels are studied, so cohort differences can reflect more than dose. General possibilities include changes in study experience or chance variation; the registry record does not say whether any particular factor affected these results. The counts therefore describe what was observed in each cohort, without isolating a dose effect.
Open-label means masking was not used. In general, knowledge of treatment can influence reporting, assessment, or decisions about whether an event is related, although the registry does not establish that this occurred in this study. A comparison of adverse-event counts should account for the study design and ascertainment process, not just the raw values. No randomized comparison or adjusted cohort analysis is reported in the registry record.
What does uncertainty mean for these counts?
Observed counts are estimates of experience in the enrolled study population, not guarantees about future patients. In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. The registry record does not report confidence intervals for the cohort counts, so no interval-based precision claim can be made from the posted results. With only 5 participants at risk in each cohort, the descriptive counts are especially sensitive to the experience of individual participants. This is a general interpretation of small cohort counts, not a separate calculated result.
A zero count means no participant in that cohort was recorded with the specified outcome during the reported observation period. It does not show that the outcome is impossible or that its underlying risk is zero. Likewise, a nonzero count is not by itself proof that treatment caused the event. Causal conclusions require a design and analysis that support separating treatment effects from other explanations. The registry record does not report such a comparison.
How should planning calculations be understood?
General sample-size calculations estimate how much information a future study might need under specified assumptions. The planning illustration associated with the posted material uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers an effect defined as a stated fraction of the observed effect. Such assumptions are not descriptions of the study’s actual sequential design, and a planning calculation is not an observed result. Any sample sizes from such an illustration would be planning quantities, not participants observed in this study and not evidence of observed power. The registry record does not report that these assumptions formed part of the original trial design or its statistical plan.
For adverse-event data, the choice of analysis also depends on whether the target is the number of affected participants, the number of event episodes, event timing, or severity. Those are not interchangeable outcomes. The posted primary measure is participant-based, and the record does not report a model for event counts, time to event, or cohort comparison. There is therefore no basis to describe a fitted statistical model, adjustment strategy, or hypothesis test as part of the reported analysis.
In general, a p-value assesses compatibility between data and a specified null model under the assumptions of a test; it does not measure clinical importance or prove causality. No p-value or inferential analysis result is reported in the registry record. The cohort counts are consequently most appropriately read as descriptive evidence, with uncertainty and design limitations stated explicitly rather than implied away by a formal test.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes several safety categories: treatment-emergent events, events considered related to study drug, serious events, related serious events, events leading to withdrawal, related events leading to withdrawal, serious events leading to withdrawal, and events leading to death. Looking at multiple outcomes creates a multiplicity issue when formal statistical claims are made. In general, testing many outcomes can increase the chance of finding an apparently notable result by chance. Whether and how that concern should be controlled depends on the planned analyses and the purpose of each endpoint.
The registry record does not report a multiplicity adjustment, a hierarchy among safety outcomes, or a statistical analysis plan. It also does not report an inferential analysis for the cohort counts. The posted results should therefore be treated as descriptive rather than as a set of confirmatory tests. The record does not say whether interim analyses were planned or conducted.
The safety population is defined as all patients who received at least one dose of study drug. Cohort-level counts are reported with 5 participants at risk in each cohort. The registry record does not provide detailed participant flow, reasons for any exclusions from safety analyses, or an account of missing outcome data. It does not report how incomplete follow-up or missing adverse-event information was handled. These details matter because a participant with unobserved follow-up may have had an event that was not captured in the recorded count.
The record’s definition of the safety population is not a substitute for a missing-data description. The registry record does not report sensitivity analyses or methods for addressing missingness. Without those details, the degree to which incomplete observation could affect the counts cannot be assessed. No conclusions about the absence of unreported events or the robustness of the endpoint to missing data are supported.
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 |
|---|---|---|---|
| Cohort 1 | 0 | 5 | 0.0% |
| Cohort 2 | 0 | 5 | 0.0% |
| Cohort 3 | 1 | 5 | 20.0% |
| Cohort 4 | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 | 0 of 5 |
| Cohort 2 | 0 of 5 |
| Cohort 3 | 0 of 5 |
| Cohort 4 | 0 of 5 |
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 |
|---|---|
| Cohort 1 | 2 of 5 |
| Cohort 2 | 1 of 5 |
| Cohort 3 | 5 of 5 |
| Cohort 4 | 4 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 5 |
| Vomitting | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 1 of 5 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 1 of 5 | 0 of 5 | 2 of 5 | 2 of 5 |
| Nasopharyngitis | Infections and infestations | 0 of 5 | 1 of 5 | 2 of 5 | 1 of 5 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 5 | 1 of 5 | 1 of 5 | 1 of 5 |
| Flushing | Vascular disorders | 0 of 5 | 0 of 5 | 1 of 5 | 1 of 5 |
| Diarrhoea | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 2 of 5 | 0 of 5 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 1 of 5 | 1 of 5 |
| Vomiting | Gastrointestinal disorders | 0 of 5 | 0 of 5 | 1 of 5 | 1 of 5 |
| Fall | Injury, poisoning and procedural complications | 1 of 5 | 0 of 5 | 0 of 5 | 0 of 5 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 0 of 5 | 0 of 5 | 0 of 5 | 1 of 5 |
| Presyncope | Nervous system disorders | 0 of 5 | 0 of 5 | 0 of 5 | 1 of 5 |
Serious events with the highest arm-level rate: diarrhoea (20.0%), vomitting (20.0%).
The serious adverse-event counts are 0 in Cohort 1, 0 in Cohort 2, 1 in Cohort 3, and 0 in Cohort 4; the number at risk is 5 in each cohort. These are cohort-level counts of participants with the outcome, not counts of all serious-event episodes. The registry also reports 0 deaths in each cohort. A zero count describes what was recorded during the observation period; it does not establish that the underlying possibility of an event is zero.
The registry lists Diarrhoea and Vomitting as serious adverse-event terms, each at 20.0%. The record does not identify those term percentages with a particular cohort in the information. They should therefore be kept separate from the cohort counts rather than assigned to one of the dose levels.
Seriousness does not establish that an event was caused by the study drug. The endpoint description distinguishes serious events from serious events considered related to study drug, but separate related-event counts by cohort are not reported in the posted results. With no reported randomized control group, the counts also cannot show whether serious events occurred more often than they would have without treatment. The figures are useful for describing recorded safety observations, but they do not support a causal risk comparison.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry recorded adverse-event counts in four sequential cohorts and serious-event counts in those cohorts. The serious-event count was 0 in Cohort 1, 0 in Cohort 2, 1 in Cohort 3, and 0 in Cohort 4; deaths were recorded as 0 in each cohort. For the other adverse-event count, the reported values were 2 in Cohort 1, 1 in Cohort 2, 5 in Cohort 3, and 4 in Cohort 4. Each cohort had 5 participants at risk. These findings describe the study observations for the stated follow-up, which extended up to 6 weeks from first administration.
They do not establish that rimeporide caused or prevented an event. The study was open-label and sequential, and the registry record does not report a randomized control group. Differences between cohorts cannot be interpreted as a controlled dose comparison, because cohort order and other possible influences are not separated by a reported comparative analysis. Nor do the counts establish how the drug would perform in a broader patient population.
The counts do not describe every dimension of safety. They are participant counts, not a complete account of event frequency, timing, duration, recurrence, or course. The record does not report cohort-specific values for each relatedness and withdrawal category listed in the endpoint description, or detailed narratives that would support further interpretation. The serious-event terms are listed at 20.0% each, but are not linked to a specific cohort in the reported information.
Statistical precision is also limited by the small cohort sizes and by the absence of reported confidence intervals or inferential analysis. A lack of a recorded serious event in a cohort should not be read as proof that such events cannot occur; a recorded event should not be treated as proof of causation. The most defensible conclusion is descriptive: the registry reports the stated counts within this study and does not provide the comparative evidence needed to draw stronger causal or population-level conclusions.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a safety description and a controlled treatment comparison. The registry reports counts of participants with adverse events across sequential cohorts, which can characterize what was observed during the study. But the same counts do not answer whether rimeporide changed the chance of an event relative to a control condition. That distinction is important whenever results from an open-label, nonrandomized design are interpreted.
The sequential dose structure also affects interpretation. Cohorts were studied in ascending order, so dose level and cohort order are linked. Without a randomized control group or a reported adjusted analysis, cohort-to-cohort differences cannot isolate a dose-related pattern. The design may be useful for an early safety and tolerability assessment, but the record does not report a formal comparison that would justify treating those differences as treatment effects.
The endpoint itself highlights another statistical distinction: participant counts are not event totals. Counting participants with at least one event answers how many people were affected, while event-episode counts would answer a different question about recurrence or overall burden. The registry’s primary endpoint is a participant count, and conclusions should remain aligned with that measure.
Finally, the record underscores the value of reporting uncertainty and analysis details. Cohort counts are presented, but confidence intervals, inferential tests, handling of missing data, and a statistical analysis plan are not reported in the registry record. These omissions limit precision and make it difficult to evaluate how robust the descriptive findings are. Recognizing those limits is part of sound interpretation, rather than a reason to overstate what the results demonstrate.
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 study is open-label, and masking is listed as none. This can matter for event reporting and assessment, particularly for judgments about whether an event was related to study drug. The registry record does not describe procedures used to reduce assessment bias. It also does not report a randomized control group, so the observed counts cannot be interpreted as a controlled comparison.
The sequential design links cohort membership to dose order. The record says dose levels were studied in ascending order, but the cohort-specific dose amounts are not reported alongside the outcome counts. Since order and cohort are linked, differences in counts cannot be attributed to dose alone. No adjustment or formal comparison is reported in the registry record.
Each cohort has 5 participants at risk in the posted adverse-event counts. Such small cohort counts offer limited precision, and the registry record does not report confidence intervals for them. It also does not report detailed participant-level event histories, timing, duration, recurrence, or all category-specific cohort counts. The term percentages for Diarrhoea and Vomitting are not linked to a specific cohort in the information.
The registry defines the safety population as participants who received at least one dose, but it does not report detailed follow-up completeness or how missing adverse-event information was handled. A statistical analysis plan, multiplicity approach, and interim-analysis information are also not reported in the registry record. These limitations leave uncertainty about the completeness and analytic context of the posted results. They support a cautious, descriptive reading rather than a causal or population-wide conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Rimeporide in Patients With Duchenne Muscular Dystrophy — NCT02710591.
- Registry record last updated 2019-07-18; status last verified 2019-01.
- Results first posted 2019-07-18.
- 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
NCT02710591 is a completed phase Ib, open-label study of rimeporide in patients with Duchenne muscular dystrophy. The registry lists enrollment of 20 and describes four sequential, ascending dose cohorts. Oral doses ranged from 50 to 300 mg, were administered three times a day for 4 weeks, and were assessed for safety and tolerability. The primary endpoint counted participants with adverse events during follow-up of up to 6 weeks from first administration.
For serious adverse events, the cohort counts were 0, 0, 1, and 0; deaths were recorded as 0 in each cohort. Other adverse-event counts were 2, 1, 5, and 4. There were 5 participants at risk in each cohort. The registry does not report a randomized comparison, inferential analysis, confidence intervals, statistical analysis plan, or detailed missing-data methods. The findings are therefore descriptive observations from sequential cohorts, not a controlled estimate of treatment effect.