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 Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration (NCT02174848), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02174848 |
| Phase | Phase 3 |
| Condition | Pantothenate Kinase-Associated Neurodegeneration |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 68 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ApoPharma |
| Results posted | Yes |
2. Clinical Question
Population
People with pantothenate kinase-associated neurodegeneration (PKAN) who had completed the earlier study TIRCON2012V1 (NCT01741532) were eligible. The safety population included 68 participants.
Intervention
All participants received deferiprone oral solution during this 18-month study. The registry record does not report a dose in the study details.
Comparator
There was no concurrent comparator group: the study used a single-group design, and all participants received deferiprone. Some secondary outcomes compare groups or treatment histories across studies, including participants previously assigned placebo or deferiprone.
Primary question
How many participants experienced adverse events during treatment, as part of the assessment of safety and tolerability over 18 months? The registry description also identifies serious adverse events and discontinuation due to adverse events as safety measures. It states that no statistical comparison between groups was conducted.
The central interpretive issue is that the study describes adverse events during treatment in a selected group of previous-trial completers. It does not compare concurrent deferiprone and placebo groups. Therefore, the event counts describe what was recorded among participants in this study; by themselves, they cannot establish how those counts would compare with outcomes under another treatment or no treatment.
Eligibility was tied to completing the earlier double-blind placebo-controlled study. The earlier study randomized participants to deferiprone or placebo for 18 months, but that randomization does not create a concurrent control group in this follow-on study, where everyone received deferiprone. Secondary outcomes include comparisons across the earlier and current studies, including comparisons by prior treatment history. Those comparisons differ from a randomized comparison within this study and should be interpreted in light of their cross-study nature.
3. Trial Design
The registry identifies this as a Phase 3, single-group study of long-term deferiprone treatment in people with PKAN. The planned treatment period was 18 months, and the intervention was deferiprone oral solution. The study enrolled 68 participants. The registry status is completed.
Eligibility was restricted to people who had completed TIRCON2012V1 (NCT01741532), an earlier double-blind, placebo-controlled study lasting 18 months. Participants in that earlier study had been randomized to deferiprone or placebo. In the current study, however, all participants received deferiprone. The earlier randomization is relevant background, but it is not a randomized treatment allocation for this study.
The registry lists allocation as not applicable, masking as none, and the model as single group. Thus, the primary safety findings are descriptive rather than a comparison between concurrently assigned groups. The record describes no statistical comparison between groups because all participants received the same study product. The rationale for the enrollment target, any formal sample-size justification, and any planned interim analyses are not reported in the registry record.
Beyond the primary adverse-event measure, the listed secondary outcomes concern changes in BAD Scale scores, the proportion with improved or unchanged BAD scores, and Patient Global Impression of Improvement. Several secondary outcomes compare treatment groups or compare participants’ histories across the earlier and current studies. Those are distinct from a parallel-group comparison conducted within the current study. The registry record does not establish that such cross-study comparisons retain the protections of the earlier randomization after participants entered this single-group follow-on study.
These design details set the scope for interpretation: the study can describe events and outcomes observed during follow-on deferiprone treatment in eligible participants. Without a concurrent control group, it cannot isolate the treatment’s effect from other explanations for observed changes or events.
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 | Placebo-DFP | DFP-DFP |
|---|---|---|
| STARTED | 24 | 44 |
| Provided Post-baseline Efficacy Data | 19 | 43 |
| COMPLETED | 17 | 38 |
| NOT COMPLETED | 7 | 6 |
Reasons for not completing this period:
| Reason | Placebo-DFP | DFP-DFP |
|---|---|---|
| Adverse Event | 2 | 1 |
| Withdrawal by Subject | 3 | 3 |
| Lost to Follow-up | 0 | 1 |
| Worsening of disease | 1 | 1 |
| Unable to comply with study requirements | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population
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-DFP | DFP-DFP | Total |
|---|---|---|---|---|
| Participants analysed | 24 | 44 | 68 | |
| Age, Continuous | years | 19.9 (SD 13.0) | 22.4 (SD 9.6) | 21.5 (SD 10.9) |
| Sex: Female, Male: Female | Participants | 14 | 16 | 30 |
| Sex: Female, Male: Male | Participants | 10 | 28 | 38 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 22 | 41 | 63 |
| Race (NIH/OMB): More than one race | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| BAD score at baseline: BAD score at baseline of initial study | units on a scale | 16.0 (SD 8.0) | 19.4 (SD 8.1) | 18.3 (SD 8.2) |
| BAD score at baseline: BAD score at baseline of extension study | units on a scale | 20.4 (SD 8.2) | 21.3 (SD 7.6) | 21.0 (SD 7.7) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over 18 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events, measured over 18 months in the safety population. The registry description says safety and tolerability were assessed using changes in the frequency of adverse events, the frequency of serious adverse events, and discontinuation due to adverse events. The posted primary result is a count of participants, not a treatment-effect estimate from a comparison between groups.
Counting participants who experienced an event is a direct way to describe how many people in the study had at least one recorded event in the relevant category. It answers a descriptive safety question about the study population. It does not, on its own, show how often events occurred relative to another treatment, nor does it convey the total number of repeated events experienced by each participant. A participant count and an event count are different summaries: one person can experience more than one event, while a count of participants records that person once for a given category.
General statistical context: adverse-event counts are useful because they put safety observations in terms of people affected. Their interpretation still depends on the population observed, follow-up, and how events were classified and collected. Here, the registry specifies an 18-month timeframe and a safety population of 68 participants. It does not report a concurrent control group or a statistical comparison, so the endpoint is best read as a description of recorded events during treatment rather than an estimate of comparative risk.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The safety record reports that, among 68 participants at risk, 33 had serious adverse events and 66 had other adverse events. These are participant counts. They indicate that adverse events were recorded among participants during the study, but the counts are not a treatment-versus-control contrast. All participants received deferiprone, and the registry explicitly states that no statistical comparison between groups was conducted.
The two deaths are reported as a separate count. The registry information does not state whether the deaths were considered related to treatment, whether they were included among the participants with serious adverse events, or what circumstances surrounded them. The count therefore should not be interpreted as evidence about cause. Likewise, event occurrence during a treatment period does not by itself establish that treatment caused the event.
The serious-event terms listed most often are dystonia (11.8%), neutropenia (5.9%), gastrostomy (5.9%), pyrexia (4.4%), medical device implantation (4.4%), and bronchitis (2.9%). These are registry-reported percentages attached to event terms. The record excerpt does not explain whether each percentage refers to participants or events, or whether participants could contribute to more than one term. It is therefore important not to add these percentages or treat them as mutually exclusive categories.
Precision is limited by the descriptive design and the number of participants observed. Without a concurrent comparison group, there is no within-study estimate of how the event counts differ from an alternative treatment or background event occurrence. A confidence interval, when reported for an estimate, describes statistical uncertainty under the method used; it does not remedy the absence of a comparator or account automatically for differences between populations. The registry record does not report a comparative safety estimate or a confidence interval for these counts.
Eligibility also shapes the population to which the findings apply. Participants had completed an earlier study, so these observations concern that selected group of completers rather than all people with PKAN. The available record does not report how many otherwise eligible people did not enter the follow-on study or provide characteristics that would allow assessment of how participants who enrolled differed from those who did not.
Overall, the posted results describe adverse events recorded during 18 months of deferiprone treatment in this study population. They do not establish whether deferiprone increases, decreases, or has no effect on adverse-event occurrence relative to a control condition. Such causal or comparative conclusions require evidence beyond these single-group counts.
9. Statistical Methods Explained
The registry reports a participant-count endpoint and a single-group design. The key statistical distinction is between describing the number of people with events and estimating a treatment contrast. These results do the former. Since all participants received deferiprone, the study has no concurrent group from which to calculate a within-study difference in event occurrence between treatments.
What does a participant count describe?
A participant count records how many people experienced an event in a defined category during the specified follow-up. It is not the same as the total number of events. For example, one participant with repeated events may contribute one person to a participant count while contributing multiple events to an event total. The primary endpoint is explicitly a count of participants with adverse events. The registry separately describes serious and other adverse-event counts and discontinuation due to adverse events as safety measures, but does not give a discontinuation count in the registry record.
General explanation: a count is easiest to interpret when its denominator, follow-up period, and event definition are clear. The record identifies 68 participants at risk and an 18-month timeframe for the primary endpoint. A count alone does not communicate the timing of events, the number of repeated episodes, or how long each participant remained under observation. Those details are not reported in the registry record.
Why does the single-group design matter?
In a comparative trial, an outcome in one group can be contrasted with an outcome in another group, subject to the design and analysis. Here, all participants received the same study product, and the record says no statistical comparison between groups was conducted. Consequently, the event counts describe what happened among those treated in the study; they do not estimate a difference attributable to treatment.
General explanation: random assignment in a concurrent comparison can help balance measured and unmeasured factors across treatment groups on average. A follow-on study that enrolls only people who completed an earlier trial and then treats everyone alike does not maintain that concurrent comparison. Even if participants had different assignments in the earlier study, the current study is not a randomized comparison of those earlier assignments during its treatment period. Cross-study comparisons can be affected by changes in follow-up, participant selection, study context, and other differences; the registry record does not report an adjustment strategy that addresses these issues.
How should uncertainty be understood?
General explanation: statistical uncertainty reflects the fact that results from a study population may not equal the corresponding quantities in a broader population. A confidence interval, when available, gives a range of estimates compatible with the data and the method’s assumptions. It does not measure every source of uncertainty, and it cannot create a control group where none exists. The registry record does not report a confidence interval or comparative estimate for the adverse-event counts.
General explanation: for event counts, precision depends in part on how many people were observed and how common the event category was. Less frequent events are generally represented by fewer observations and may therefore be estimated less precisely. A count should not be mistaken for a precise estimate of the underlying frequency in all people with PKAN. The single-group design also leaves the comparative question unanswered regardless of the precision of a descriptive count.
What can planning calculations tell readers?
Any sample-size illustrations associated with this analysis are planning exercises based on an observed effect, not the design justification for this trial. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. Such illustrations do not represent observed power, and they should not be read as evidence that the study was designed or powered for a comparison that it did not conduct.
General explanation: a planning calculation asks how many participants a hypothetical study might need under specified assumptions to detect a target effect with a chosen statistical procedure. The result depends on those assumptions and is not a retrospective measure of how likely a completed study was to find a statistically significant result. Here, the registry record does not report the original sample-size justification or a planned two-arm design for the follow-on study.
Why do outcome definitions and analysis choices matter?
Safety summaries depend on how adverse events and serious adverse events are defined, collected, coded, and assigned to categories. The record gives selected serious-event terms and participant counts but does not describe the coding rules, event adjudication, or the detail of the collection process. The listed event-term percentages should therefore be interpreted as registry summaries, not as a complete account of event severity, timing, duration, or attribution.
The record lists BAD Scale outcomes and Patient Global Impression of Improvement among secondary outcomes. The presence of multiple outcomes raises general questions about how analyses were planned and how uncertainty across several tests should be interpreted. The statistical analysis plan, any prespecified hierarchy, and any multiplicity adjustment are not reported in the registry record. No inferential result for these secondary outcomes is included in the registry record for this explanation, so their estimates or significance cannot be characterized.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes: changes in BAD Scale scores, comparisons involving participants’ treatment histories across the earlier and current studies, the proportion with improved or unchanged BAD scores, and a Patient Global Impression of Improvement comparison across studies. Considering multiple outcomes can increase the chance that at least one apparently notable result arises by chance when many tests are conducted. General statistical methods for addressing this include prespecifying a primary outcome, using a testing hierarchy, or adjusting for multiple comparisons. Which methods were planned or used is not reported in the registry record.
The registry gives a primary safety endpoint and describes no statistical comparison between groups because all participants received the same study product. The statistical analysis plan, any interim analyses, and any multiplicity strategy are not reported in the registry record. Therefore, the scope and decision rules for inferential testing cannot be reconstructed from the information.
The record identifies a safety population of 68 participants and states the study timeframe, but the handling of missing outcome data, withdrawals, incomplete follow-up, or participants with differing observation time is not reported in the registry record. The number who discontinued because of adverse events is not stated in the registry record, although the endpoint description says discontinuation due to adverse events was assessed. It is also not reported whether the primary count required any particular minimum follow-up or how missing event information was handled.
These omissions matter because incomplete follow-up can affect event counts and the interpretation of outcome changes. General explanation: an analysis limited to participants with complete measurements may differ from one that uses all available observations or accounts for missingness, and each approach depends on assumptions. Without the analysis details, the direction or size of any such impact cannot be inferred. No assumptions about missingness or corrections for multiple testing should be attributed to the study without a reported plan.
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 |
|---|---|---|---|
| All Patients | 33 | 68 | 48.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Patients | 2 of 68 |
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 |
|---|---|
| All Patients | 66 of 68 |
Most frequent serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Dystonia | Nervous system disorders | 8 of 68 |
| Neutropenia | Blood and lymphatic system disorders | 4 of 68 |
| Gastrostomy | Surgical and medical procedures | 4 of 68 |
| Pyrexia | General disorders | 3 of 68 |
| Medical device implantation | Surgical and medical procedures | 3 of 68 |
| Bronchitis | Infections and infestations | 2 of 68 |
| Pneumonia | Infections and infestations | 2 of 68 |
| Wound infection | Infections and infestations | 2 of 68 |
| Medical device battery replacement | Surgical and medical procedures | 2 of 68 |
| Medical device change | Surgical and medical procedures | 2 of 68 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Dystonia | Nervous system disorders | 32 of 68 |
| Pyrexia | General disorders | 20 of 68 |
| Headache | Nervous system disorders | 19 of 68 |
| Serum ferritin decreased | Investigations | 18 of 68 |
| Condition aggravated | General disorders | 17 of 68 |
| Pain in extremity | Metabolism and nutrition disorders | 14 of 68 |
| Upper respiratory tract infection | Infections and infestations | 13 of 68 |
| Anemias | Blood and lymphatic system disorders | 12 of 68 |
| Cough | Respiratory, thoracic and mediastinal disorders | 12 of 68 |
| Nasopharyngitis | Infections and infestations | 11 of 68 |
Serious events with the highest arm-level rate: dystonia (11.8%), neutropenia (5.9%), gastrostomy (5.9%), pyrexia (4.4%), medical device implantation (4.4%).
The registry reports 33 participants with serious adverse events among 68 at risk, and 66 participants with other adverse events among 68 at risk. It also reports 2 deaths. These are counts of participants or deaths as specified in the record, not comparative estimates against another treatment group. All participants received deferiprone, and the registry states that no statistical comparison between groups was conducted.
The listed serious-event terms and percentages are dystonia (11.8%), neutropenia (5.9%), gastrostomy (5.9%), pyrexia (4.4%), medical device implantation (4.4%), and bronchitis (2.9%). They are a selection of the most frequent serious terms, not a complete list of all events. The record does not explain whether the percentages refer to participants or events, whether one participant could appear under multiple terms, or how serious events were classified.
Seriousness is not the same as causation. The registry information does not state whether the serious events or deaths were judged related to deferiprone. Nor does it specify whether the deaths overlap with the serious-event participant count. The counts therefore describe safety observations during the study period; they do not establish that treatment caused or prevented any event.
12. What the Result Does, and Does Not, Mean
The result supports a narrow descriptive statement: during the 18-month study, adverse events were recorded among participants receiving deferiprone, including serious adverse events, and the registry reports counts for these categories. The safety population was 68 participants. These observations matter for describing what occurred in this group and for understanding the kinds of safety information the registry recorded.
The result does not establish a comparative treatment effect. There was no concurrent control group, and all participants received the same study product. A count among treated participants cannot show whether more or fewer events occurred than would have occurred under placebo, another treatment, or no treatment. The earlier study had randomized placebo and deferiprone assignments, but the current study enrolled completers and treated all participants with deferiprone; it is not a continuation of a randomized comparison during the current follow-up.
The counts also do not establish that deferiprone caused the events. Events occurring during treatment can have multiple possible explanations, and the registry information does not give causality assessments. The deaths are reported as a count, without information in this record about cause or attribution. Likewise, the serious-event terms and percentages do not by themselves describe severity beyond their classification, timing, duration, or clinical course.
General explanation: statistical precision and causal interpretation are separate issues. A descriptive count may be measured clearly for the participants observed yet still fail to answer what would have happened to those same participants under a different treatment. Comparative inference needs an appropriate comparison and an analysis suited to the design. More precise description cannot substitute for the missing counterfactual comparison.
The population is also selected: eligibility required completion of the earlier study. The results therefore describe enrolled completers, not necessarily all people with PKAN or all people who might be considered for treatment. The registry record does not report enough information to assess how participants who entered this follow-on study differ from people who did not. The most defensible interpretation is consequently limited to the reported safety experience in the study population, without claims about efficacy or comparative safety.
13. Why This Trial Matters Statistically
This study is statistically important because it illustrates the difference between continued treatment observation and randomized comparative evidence. Participants came from an earlier randomized study, but this follow-on study used a single-group design in which everyone received deferiprone. The earlier trial context does not turn the current safety counts into a concurrent randomized comparison.
That distinction is especially relevant when interpreting long-term safety information. Descriptive follow-up can document events in people who continue into a later study and can identify categories that merit careful reporting. At the same time, selection based on completion of the earlier study means the enrolled group is defined by a prior study history. Results in this group should not automatically be generalized to all people with PKAN.
The record also shows why endpoint type matters. A count of participants with adverse events answers how many people were recorded as affected in a category; it does not report the total burden of repeated events or estimate a relative risk. Likewise, serious-event terms and deaths should be read as reported observations, without assuming treatment causality where the record does not report attribution.
General statistical context: researchers and readers need to match each conclusion to the design and estimand. A single-arm study can provide descriptive information, while a causal contrast generally requires a suitable comparison and assumptions that support that contrast. The registry record does not report a comparative analysis for the primary safety endpoint. Thus, the key statistical contribution is documentation of the observed safety experience in this follow-on population, not a treatment-effect estimate.
Finally, this study highlights the importance of transparent analysis details. Information about missing data, event classification, multiplicity, and analysis populations helps readers understand how reported outcomes were constructed. Where those details are not reported in the registry record, interpretation should remain bounded by the counts and design information that are available.
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 trial-specific limitation is the absence of a concurrent control group. Because every participant received deferiprone, the safety counts cannot estimate a within-study difference between treatments. The registry explicitly states that no statistical comparison between groups was conducted.
Enrollment was limited to people who had completed the earlier study. This eligibility condition creates a selected follow-on population and limits how directly the findings can be applied to people with PKAN who were not earlier-trial completers. The registry information does not report the characteristics of people who were eligible but did not enroll, or allow assessment of how they differed from participants.
The event summaries are limited in detail. The record reports counts for serious and other adverse events, selected serious-event terms with percentages, and 2 deaths, but does not report event timing, duration, repeated-event counts, relatedness assessments, or circumstances of death in the registry record. It also does not clarify whether the listed term percentages describe participants or events, or whether categories overlap. The number discontinuing due to adverse events is not reported in the registry record.
The available information does not specify how incomplete follow-up or missing outcome data were handled, whether event classification was independently reviewed, or what statistical analysis plan governed the secondary outcomes. The study’s sample-size justification and any interim analyses are not reported in the registry record. These gaps prevent a full assessment of analysis choices and precision beyond the reported descriptive counts.
Finally, the secondary outcomes include comparisons across study periods and prior treatment histories. Those comparisons are not the same as a randomized comparison within this follow-on study. Their interpretation depends on details of eligibility, follow-up, and analysis that are not reported in the registry record. These limitations do not negate the descriptive observations, but they constrain comparative and causal conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration — NCT02174848.
- Registry record last updated 2020-08-25; status last verified 2020-08.
- Results first posted 2019-07-17.
- 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
NCT02174848 is a completed Phase 3, single-group study of long-term deferiprone treatment in people with PKAN. Participants had to complete the earlier TIRCON2012V1 study, and all participants in this study received deferiprone oral solution for an 18-month treatment period. The safety population included 68 participants.
The primary endpoint was the number of participants with adverse events. The registry reports 33 participants with serious adverse events, 66 with other adverse events, and 2 deaths. It lists dystonia, neutropenia, gastrostomy, pyrexia, medical device implantation, and bronchitis among the most frequent serious-event terms. The record states that no statistical comparison between groups was conducted because all participants received the same study product.
The findings describe recorded events in this selected follow-on population. They do not provide a concurrent treatment comparison or establish that deferiprone caused or prevented the reported events. Further details about missing data, event attribution, the analysis plan, and sample-size justification are not reported in the registry record.