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 Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD) (NCT01027884), a randomized phase 3 study. The primary outcome is Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01027884 |
| Phase | Phase 3 |
| Condition | Muscular Dystrophy, Duchenne, Ambulatory Care |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 65 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Santhera Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients aged 10–18 years with Duchenne muscular dystrophy were the stated study population. The primary analysis description identifies an ITT population of patients who were randomized, received at least one dose of study medication, and had at least one post-baseline assessment. It also says that siblings allocated to the same treatment as a randomized patient were excluded from that analysis.
Intervention
Idebenone was given at 900 mg/day. The registry describes the study as randomized, quadruple-masked, and parallel-group, and the official title identifies it as double-blind.
Comparator
The control group received placebo at 900 mg/day. This provides the trial’s comparison condition; the registry does not report additional details about treatment duration or medication schedules.
Primary question
The primary endpoint was change from baseline in percent-predicted peak expiratory flow (PEF) at Week 52. The registry reports group-specific estimates and confidence intervals, but not a direct between-group estimate for this endpoint. The posted figures therefore describe the outcome in each group; they do not, on their own, quantify the estimated difference between treatments or establish whether that difference is statistically distinguishable from no difference.
3. Trial Design
This was a Phase III, randomized, parallel-group study comparing idebenone with placebo in Duchenne muscular dystrophy. The official title describes it as double-blind and placebo-controlled; the registry’s masking classification is quadruple. These descriptions indicate that masking was part of the design, but the registry record does not identify which roles were masked or give further operational details.
The intervention and placebo were each listed at 900 mg/day. The registry records enrollment of 65 and a primary completion date of 2014-01. The study start is recorded as 2009-07, and the status is completed. These registry entries describe the trial’s record and timeline; they do not provide a full account of recruitment, follow-up, or treatment exposure.
The primary outcome was change from baseline in percent-predicted PEF at Week 52. Other listed outcomes include change in percent-predicted forced vital capacity at Week 52, change in muscle strength, change in quality of life assessed by PedsQL, and the percentage of patients reporting adverse events. The record lists four secondary outcomes, but numerical results for these outcomes are not reported in the registry record.
The primary analysis population is described as ITT, with eligibility requiring at least one dose and at least one post-baseline assessment after randomization. The description also excludes siblings allocated to the same study treatment as a randomized participant. The registry record does not provide a fuller protocol account, such as allocation procedures, adherence summaries, or details of visit schedules.
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: 65 patients were randomly assigned and two patients were allocated to the same treatment as their randomly assigned siblings. One patient never took study medication, resulting in 66 patients who were treated and included in the safety population (34 in the placebo group and 32 in the idebenone group).
Overall Study
| Stage | Placebo | Idebenone |
|---|---|---|
| STARTED | 34 | 32 |
| COMPLETED | 30 | 25 |
| NOT COMPLETED | 4 | 7 |
Reasons for not completing this period:
| Reason | Placebo | Idebenone |
|---|---|---|
| Adverse Event | 2 | 1 |
| Protocol Violation | 1 | 0 |
| Non-compliance | 1 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Lost to Follow-up | 0 | 1 |
| Spinal fixation surgery | 0 | 3 |
Analysis population for the primary outcome, as defined in the registry: This analysis was performed on the ITT population(n=64). This population included all randomized patients who received at least one dose of the study medication and provided at least one post-Baseline assessment. It excluded siblings who had been allocated to the same study treatment as a randomized sibling.
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 | Placebo | Idebenone | Total |
|---|---|---|---|---|
| Participants analysed | 34 | 32 | 66 | |
| Age, Continuous | years | 15 (SD 2.5) | 13.5 (SD 2.7) | 14.3 (SD 2.7) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 34 | 32 | 66 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52, measured over Baseline and Week 52.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage |
| Endpoint classification | not reduced to a single comparison |
Peak expiratory flow (PEF) is a measure of how quickly a person can expel air from the lungs during a forceful breath. The primary endpoint expresses PEF as a percentage of a predicted value and assesses its change from baseline at Week 52. Expressing lung function relative to a predicted value can help describe measurements in the context of a reference expectation, while a change-from-baseline endpoint focuses on how the measure shifted over the study period.
The registry reports the endpoint as a geometric-mean change in percent-predicted PEF, with a 95% confidence interval for each group. For placebo, the reported estimate is -8.84 with a 95% confidence interval from -12.73 to -4.95. For idebenone, the estimate is -2.57 with a 95% confidence interval from -6.68 to 1.54. These are group-specific results, not a direct treatment contrast.
PEF is relevant to the study’s stated focus on pulmonary function. However, a within-group change does not by itself establish the comparative effect of the assigned treatments. That requires an analysis of the between-group contrast, with its uncertainty and any specified adjustment. The registry record does not report that contrast for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results describe change in percent-predicted PEF from baseline to Week 52. The reported estimate is -8.84 for placebo and -2.57 for idebenone. Both point estimates are below zero, while the 95% confidence interval for idebenone extends across zero; the placebo interval is entirely below zero. These statements concern each group’s estimate relative to baseline, not the difference between groups.
The intervals communicate uncertainty around the group-specific estimates. The placebo interval runs from -12.73 to -4.95, and the idebenone interval runs from -6.68 to 1.54. Their ranges overlap. Interval overlap is not a substitute for a formal between-group test, and it does not provide the test result or confidence interval for a treatment contrast. The registry record does not report a direct between-arm estimate, its confidence interval, or a p-value for the primary endpoint.
The point estimates differ in direction of magnitude: the idebenone estimate is closer to zero than the placebo estimate. That descriptive comparison should not be mistaken for an estimated treatment effect. Without a reported contrast and its uncertainty, the posted figures do not show how precisely the between-group difference was estimated or whether it meets a prespecified statistical criterion. The registry record also does not report a statistical analysis plan or a threshold for clinical importance.
The estimates are reported as geometric means. The record does not explain the transformation or calculation details behind that summary, so the estimates should be interpreted in the form reported rather than reinterpreted as arithmetic averages. The primary population is described as ITT, but with the stated requirements of receiving at least one dose and having a post-baseline assessment, and with the stated sibling exclusion. Those qualifications matter when considering what population the estimates describe.
The registry lists secondary outcomes related to forced vital capacity, muscle strength, quality of life, and adverse events. Numerical results for the secondary efficacy outcomes are not reported in the registry record. As a result, the primary outcome figures alone cannot describe the full set of planned clinical outcomes. They also do not establish whether the observed changes are clinically important, whether they are attributable to treatment assignment, or how they compare with results from other studies.
9. Statistical Methods Explained
Statistical methods determine how trial observations are summarized, how groups are compared, and how uncertainty is expressed. The registry record gives selected outcome summaries but does not report a full statistical analysis plan. The explanations below distinguish general statistical principles from details explicitly recorded for this study.
What does a confidence interval convey?
In general, a confidence interval describes uncertainty around an estimate under the assumptions of the analysis method. A narrower interval indicates greater precision than a wider interval, while an interval spanning a range of values makes clear that the estimate is not exact. A 95% confidence interval is a method-based summary; it does not mean that 95% of individual participants’ measurements fall within the interval, nor does it directly give the probability that a particular treatment effect is true.
For this endpoint, the registry reports a 95% confidence interval for each group’s geometric-mean change. Those intervals address uncertainty around the separate group estimates. They are not confidence intervals for the difference between idebenone and placebo. A formal comparative analysis would estimate that difference and its uncertainty directly. The registry record does not report those comparative statistics.
Why distinguish within-group changes from a treatment contrast?
General statistical interpretation separates change within a group from the contrast between groups. A group can change from baseline for many reasons, including the passage of time and features of the study population. A randomized comparison is intended to assess differences associated with assignment, but the estimate relevant to that question is the between-group contrast, analyzed according to the specified method. Comparing the signs or sizes of two separate within-group estimates is not equivalent to calculating that contrast. No recalculated contrast is presented for this record.
The registry identifies the outcome parameter as a geometric mean. In general, geometric summaries can be useful when data are analyzed on a multiplicative or transformed scale, but their interpretation depends on the measurement and analysis procedures. The registry record does not report the transformation, model, covariates, or detailed derivation of the estimates. It is therefore appropriate to retain the reported description and avoid assigning an unreported model to the analysis.
What does randomization contribute?
In general, random allocation aims to make treatment groups comparable at the start of a trial, reducing the risk that treatment assignment is systematically linked to participant characteristics. Masking can also limit some forms of expectation or assessment bias. The registry records randomized allocation, a parallel model, and quadruple masking; the official title calls the study double-blind. The record does not describe the allocation sequence, concealment procedures, or which people were masked, so those implementation details are not reported in the registry record.
Randomization does not remove uncertainty from the results, guarantee that every feature is balanced, or replace a clear analysis of the assigned groups. The population description for the primary result applies eligibility conditions after randomization and excludes specified siblings. A reader should therefore interpret the posted estimate in light of that described analysis population rather than assume that the result includes every randomized patient without qualification.
How should sample-size illustrations be read?
General sample-size calculations ask how many participants may be needed to detect a chosen effect under stated assumptions. The planning illustrations associated with the posted results are not the trial’s original design justification and are not observed power. They use the observed effect as a basis for illustration, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is set as a fraction of the observed effect. Such illustrations are conditional on these assumptions and should not be read as evidence about the probability that the completed trial detected a real effect.
The registry record does not report the original sample-size justification or whether the assumptions used for the planning illustrations were part of the trial protocol. Nor does it report a prespecified minimum clinically important difference. Those omissions prevent using the illustrations to infer what the investigators planned to detect or what magnitude would have been clinically meaningful.
Why do analysis details matter?
In general, outcome estimates depend on choices about which participants are analyzed, how missing measurements are handled, what model is used, and whether adjustments are made. Confidence intervals and tests also depend on the assumptions of the chosen method. The registry record identifies an analysis population and reports group-specific summaries, but does not give enough detail to reconstruct the analysis. It also does not report an adjusted comparison or a p-value for the primary outcome. Interpretation should therefore stay with the reported estimates and their stated uncertainty rather than imply an unreported analysis.
Over-dispersion is a general issue when observed variability exceeds what a statistical model assumes. If not accounted for, uncertainty can be understated and intervals can be too narrow. The registry record does not report whether over-dispersion was assessed or relevant to the primary endpoint, so it cannot be assumed to have occurred or to have been handled in a particular way.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary PEF endpoint and four secondary outcomes. Testing or interpreting several outcomes can raise a multiplicity issue: in general, the more statistical comparisons made, the greater the chance of finding an apparently notable result by chance if no adjustment or prespecified testing strategy is used. The registry record does not report a multiplicity procedure, a hierarchy among secondary outcomes, or a detailed statistical plan. Numerical results for the listed secondary efficacy outcomes are not reported in the registry record, so their findings cannot be assessed from this record.
The primary analysis population is described as ITT and includes randomized patients who received at least one dose and had at least one post-baseline assessment. It excludes siblings who were allocated to the same treatment as a randomized patient. These details qualify the label: the analysis description is not simply an unrestricted account of all randomized participants.
The record does not report how missing Week 52 measurements were handled, whether any imputation was used, or whether sensitivity analyses assessed the effect of missing data. It also does not report the number of missing primary endpoint measurements or reasons for missingness. Without those details, the impact of incomplete outcome data on the estimate cannot be evaluated from the registry record.
The registry lists zero posted analyses, and the primary outcome is reported as group-specific summaries rather than a direct treatment contrast. Thus, the record does not provide the analysis details needed to assess the prespecified comparative test, any covariate adjustment, or the handling of repeated or incomplete measurements. These gaps limit statistical interpretation; they do not establish that the trial did or did not perform analyses that are absent from the registry record.
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 |
|---|---|---|---|
| Placebo | 5 | 34 | 14.7% |
| Idebenone | 2 | 32 | 6.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 32 of 34 |
| Idebenone | 30 of 32 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Idebenone |
|---|---|---|---|
| Pneumonia | Infections and infestations | 2 of 34 | 0 of 32 |
| Femur fracture | Injury, poisoning and procedural complications | 1 of 34 | 0 of 32 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 34 | 0 of 32 |
| Pulmunary microemboli | Respiratory, thoracic and mediastinal disorders | 1 of 34 | 0 of 32 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 34 | 1 of 32 |
| Pyrexia | General disorders | 1 of 34 | 0 of 32 |
| Sleep apnoea syndrome | Psychiatric disorders | 0 of 34 | 1 of 32 |
| Vomitig | Gastrointestinal disorders | 1 of 34 | 0 of 32 |
| Urticaria | Skin and subcutaneous tissue disorders | 0 of 34 | 1 of 32 |
| Tendinous contracture | Musculoskeletal and connective tissue disorders | 1 of 34 | 0 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Idebenone |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 9 of 34 | 8 of 32 |
| Headache | Nervous system disorders | 7 of 34 | 6 of 32 |
| Diarrhoea | Gastrointestinal disorders | 4 of 34 | 8 of 32 |
| Bronchitis | Respiratory, thoracic and mediastinal disorders | 6 of 34 | 4 of 32 |
| Constipation | Gastrointestinal disorders | 6 of 34 | 3 of 32 |
| Pyrexia | General disorders | 3 of 34 | 5 of 32 |
| Upper respiratory tract infection | Infections and infestations | 6 of 34 | 2 of 32 |
| Gastroenteritis | Infections and infestations | 1 of 34 | 6 of 32 |
| Rhinitis | Infections and infestations | 6 of 34 | 1 of 32 |
| Abdominal pain | Gastrointestinal disorders | 3 of 34 | 3 of 32 |
Serious events with the highest arm-level rate: pneumonia (5.9%), respiratory failure (3.1%), sleep apnoea syndrome (3.1%), urticaria (3.1%), femur fracture (2.9%).
The registry reports serious adverse events for each group using counts of affected participants and the number at risk. In the placebo group, 5 participants were affected among 34 at risk; in the idebenone group, 2 were affected among 32 at risk. These are counts, not a direct estimate of the comparative risk. The registry record does not report a statistical comparison or uncertainty interval for these serious-event figures.
Listed serious-event terms include Pneumonia at 5.9%, Respiratory failure at 3.1%, Sleep apnoea syndrome at 3.1%, Urticaria at 3.1%, Femur fracture at 2.9%, and Acute respiratory failure at 2.9%. The record does not assign these listed terms to a particular treatment group in the displayed information, so they should not be interpreted as group-specific rates. The record does not report deaths.
Safety counts need context. A count of affected participants does not indicate event severity beyond the registry’s serious-event classification, timing, duration, recurrence, or relationship to study medication. The record also lists participants reporting other adverse events, but these figures do not replace a fuller account of event types and clinical context. These registry entries describe reported safety data; they do not determine whether a treatment is safe or unsafe for an individual.
12. What the Result Does, and Does Not, Mean
The primary outcome results show the reported group-specific change in percent-predicted PEF at Week 52. The point estimate is -8.84 for placebo and -2.57 for idebenone. Their confidence intervals describe uncertainty around those separate estimates, with the placebo interval below zero and the idebenone interval extending across zero. The record does not provide the direct between-group estimate needed to quantify the comparative effect.
Consequently, these results do not establish whether the difference between treatments is statistically distinguishable from no difference. No primary-outcome p-value, comparative confidence interval, or adjusted contrast is reported in the registry record. A descriptive difference between the two point estimates should not be treated as a formal treatment-effect estimate or a conclusion about clinical benefit.
The outcome is one measure of pulmonary function at one stated follow-up point. It does not, by itself, represent every aspect of respiratory function, motor function, muscle strength, quality of life, or safety. Although those domains appear among the listed outcomes, their numerical results are not reported in the registry record. The record therefore cannot support a complete assessment across all listed outcomes.
The reported analysis population has specified eligibility requirements and a sibling exclusion. The record does not report missing-data methods, the full statistical plan, or the original sample-size justification. These limitations affect how confidently readers can interpret the estimates and how well they can assess possible sources of bias or imprecision.
Statistical results are not a substitute for clinical judgment. The posted data describe what the registry records for this trial; they do not establish whether a treatment works or does not work, or give advice about treatment decisions. Any broader conclusion would require the comparative analysis and supporting information not reported in the registry record, as well as consideration of the full clinical evidence.
13. Why This Trial Matters Statistically
This trial illustrates why the format of a reported estimate matters. The primary outcome is presented as a change within each group, with a confidence interval for each estimate. The research question, however, concerns a comparison between assigned treatments. A reader needs the estimated between-group contrast and its uncertainty to evaluate that question directly. Group-specific summaries are informative about observed changes, but they do not supply that comparative result.
The record also shows how labels such as ITT require attention to operational details. Here, the analysis description includes receipt of at least one dose and a post-baseline assessment, and it excludes siblings allocated to the same treatment as a randomized patient. Stating those conditions helps readers understand who contributed to the reported primary endpoint results and cautions against assuming that every randomized participant is represented in the same way.
Multiple outcomes and incomplete data are important parts of trial interpretation, not administrative details. The registry lists secondary outcomes but does not report their numerical results or a multiplicity strategy. It does not report how missing measurements were addressed. These omissions make it difficult to judge the breadth of the evidence or the robustness of the primary estimate.
Finally, planning calculations based on an observed effect should be distinguished from the original design and from observed power. This distinction prevents retrospective illustrations from being mistaken for evidence about the trial’s prespecified aims. Together, these statistical issues show why transparent reporting of contrasts, analysis populations, missing-data methods, and analysis plans is necessary for a full interpretation of a randomized trial.
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 a direct between-group estimate for the primary PEF endpoint, its confidence interval, or a p-value. The available estimates are group-specific, which limits assessment of the primary comparative question. The record also does not report the detailed statistical model, any covariate adjustment, or the derivation of the geometric-mean summary.
The primary analysis population description has specific conditions: participants had to receive at least one dose and provide at least one post-baseline assessment, and siblings allocated to the same treatment as a randomized patient were excluded. The record does not explain the consequences of these criteria for the estimates or provide a fuller account of participants excluded from the analysis.
Missing-data methods and the amount or reasons for missing primary endpoint data are not reported in the registry record. The registry also does not report a multiplicity strategy, the original sample-size justification, an interim-analysis plan, or a prespecified clinical-importance threshold. These omissions limit assessment of the analysis decisions and the practical meaning of the observed estimates.
Numerical results for the listed secondary efficacy outcomes are not reported in the registry record. Safety information includes serious-event counts and selected terms, but the record does not report a statistical comparison or all the clinical context needed to interpret those events. It also does not report deaths. These are limitations of the record’s reported detail and should not be taken as evidence that unreported analyses or events did not occur.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD) — NCT01027884.
- Registry record last updated 2015-10-19; status last verified 2015-09.
- Results first posted 2015-10-19.
- 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
The registry identifies NCT01027884 as a completed Phase III randomized, parallel-group study of idebenone versus placebo in Duchenne muscular dystrophy. The official title describes a double-blind, placebo-controlled study in patients aged 10–18 years; the registry classifies masking as quadruple. Both arms are listed at 900 mg/day.
The primary outcome was change from baseline in percent-predicted PEF at Week 52. The record reports a geometric-mean estimate and 95% confidence interval for each group, but not a direct between-group estimate. It lists four secondary outcomes, whose numerical results are not reported in the registry record. Serious adverse-event counts are recorded for both groups, and the registry does not report deaths.
The study start is recorded as 2009-07, primary completion as 2014-01, and enrollment as 65. The primary analysis description specifies an ITT population with dose and post-baseline assessment requirements, plus a sibling exclusion. The registry record does not report the full statistical plan, missing-data methods, or original sample-size justification.