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 Ataluren for Nonsense Mutation Methylmalonic Acidemia (NCT01141075), a na phase 2 study. The primary outcome is Plasma Methylmalonic Acid (MMacid) Levels.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01141075 |
| Phase | Phase 2 |
| Condition | Amino Acid Metabolism, Inborn Errors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | PTC Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Participants with methylmalonic acidemia (MMA) due to a nonsense mutation were the population of interest. The registry describes MMA as a rare genetic disorder associated with elevated methylmalonic acid (MMacid) and explains that a nonsense mutation is a premature stop codon. The primary-outcome population is described as all randomized participants who received at least 1 dose of study drug; the number in that population is not reported in the registry record.
Intervention
The intervention was oral ataluren, an investigational drug. The registry describes the study as evaluating its safety and activity. The available dosing description gives a first cycle with treatment taken 3 times per day with meals for 28 days, followed by an interval without treatment. It also starts to describe a second cycle, but the dosing details for that cycle are incomplete in the registry record.
Comparator
No separate comparator group is described. The study model is single-group, allocation is recorded as NA, and masking is recorded as NONE. Baseline measurements can provide a within-participant reference for later measurements, but they are not a concurrent control group and cannot by themselves distinguish a treatment-related change from other changes over time.
Primary question
The primary outcome was plasma MMacid levels at baseline and at Day 28 and Day 29, the last day of dosing, in Cycles 1 and 2. The study’s stated purpose was to understand whether ataluren could safely decrease MMacid levels. The primary outcome values are not reported in the registry record, so the magnitude and direction of any change cannot be described from this record.
3. Trial Design
This was a Phase 2 study of oral ataluren for MMA due to a nonsense mutation. The registry records a single-group model, allocation as NA, and no masking. Thus, the record does not describe a randomized comparison between ataluren and a separate control treatment. The enrollment was 11. The study status is TERMINATED.
The registry lists the study start as 2010-07-19 and primary completion as 2011-11-03. These dates describe the recorded study timeline; they do not establish when every participant completed follow-up or why the study was terminated. The reason for termination is not reported in the registry record.
The intervention description specifies oral dosing with meals 3 times per day during Cycle 1 for 28 days, followed by an interval without treatment of 21 up to 42 days. The description begins to outline Cycle 2 but is truncated before its full regimen is given. Further details of the second cycle and the overall schedule are not reported in the registry record.
The primary outcome was assessed at baseline and at Day 28 and Day 29, the last day of dosing, in Cycles 1 and 2. Other listed outcomes included urinary MMacid, plasma propionylcarnitine, urine methylcitric acid, adverse events, laboratory abnormalities, metabolic decompensation episodes, treatment compliance, and ataluren plasma exposure. The registry lists 9 outcome measures. It does not report the results for the primary outcome or these secondary outcomes in the registry record for this description.
Because this is a single-group record, any change from baseline would be a within-group observation rather than an estimate from a concurrent treatment-versus-control contrast. The protocol’s detailed statistical plan, rationale for the sample size, and reason for termination are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Cycle 1
| Stage | Ataluren |
|---|---|
| STARTED | 11 |
| Received at Least 1 Dose of Study Drug | 11 |
| COMPLETED | 11 |
| NOT COMPLETED | 0 |
Cycle 2
| Stage | Ataluren |
|---|---|
| STARTED | 11 |
| Received at Least 1 Dose of Study Drug | 11 |
| COMPLETED | 11 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 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: All randomized participants who received at least 1 dose of study drug.
| Characteristic | Unit | Ataluren |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | years | 12 (SD 7.8) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Methylmalonic Acid (MMacid) Levels, measured over Baseline and Day 28 and Day 29 (last day of dosing) of Cycles 1 and 2.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | umol/L |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is plasma methylmalonic acid, abbreviated MMacid, measured in umol/L. The registry specifies a median and full range at baseline and at Day 28 and Day 29, the last day of dosing, in Cycles 1 and 2. Plasma samples were collected after a 2- to 4-hour fast and measured using a standard gas chromatography/mass spectroscopy stable-isotope dilution method. The registry describes normal plasma MMacid as <0.27 umol/L.
MMacid is relevant to the study’s stated question because the registry describes toxic elevations of this substance in MMA and says the study aimed to understand whether ataluren could safely decrease its levels. A laboratory measure can track the measured substance over time; it does not, by itself, establish a change in symptoms or other clinical outcomes. Those broader outcomes require their own measurements and interpretation.
General statistical context: the median describes the middle of an ordered set of observations and is less influenced by extreme values than the mean. A full range shows the lowest and highest observed values, but does not describe how values are distributed between those endpoints. These summaries can help describe a small or skewed set of measurements, but the underlying values and their variability matter for interpretation.
The registry record identifies the endpoint and its measurement schedule, but the observed medians and ranges are not reported in the registry record. Consequently, the size, direction, and precision of changes in plasma MMacid cannot be evaluated from the available record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the study question and design, but it does not provide the primary-outcome measurements needed to interpret the observed MMacid response. It specifies that plasma MMacid was to be summarized by median and full range at baseline and at scheduled end-of-dosing visits in Cycles 1 and 2. The actual values at those time points are not reported in the registry record. No conclusion about whether levels rose, fell, or remained similar can therefore be drawn from the information available.
The single-group design is important to interpretation. If measurements changed over time, such a pattern would describe participants receiving ataluren, but without a concurrent comparator it would not isolate the effect of treatment from other explanations. General statistical context: a control group can help account for changes that might also occur over time without the study treatment. A baseline measurement is useful as a reference, but it does not provide that concurrent comparison.
The record reports enrollment of 11 and identifies the primary-outcome population as all randomized participants who received at least 1 dose of study drug. The count included in each primary-outcome analysis, and the number of measurements available at each visit, are not reported in the registry record. This matters because summaries at different visits may be based on different sets of participants if observations are missing.
The primary endpoint is a laboratory measure, not a direct measure of symptoms, daily functioning, or longer-term clinical outcomes. The registry lists other outcomes, including adverse events and metabolic decompensation episodes, but their results are not reported in the registry record. The study’s status is TERMINATED; the reason and its implications for data collection or analysis are not reported in the registry record.
Overall, the record supports a description of a Phase 2, single-group evaluation of ataluren with a plasma MMacid outcome. It does not support a quantitative assessment of the primary outcome, a treatment-versus-control comparison, or a judgment about clinical benefit. Precision cannot be assessed because outcome estimates and uncertainty intervals are not reported in the registry record.
9. Statistical Methods Explained
What does a median and full range describe?
The primary outcome is reported in the registry as a median with a full range. General statistical context: the median is the central observation after values are ordered. It can be a useful summary when measurements are skewed or when extreme observations would pull the mean away from the typical value. The full range gives the smallest and largest observations, but it does not show whether most values cluster near the center or are spread across the interval. The registry does not report the observed medians or ranges, so these summaries cannot be evaluated for the study participants.
Reporting a summary at baseline and at later visits can describe how measurements differ over time. General statistical context: a within-participant analysis uses paired observations from the same participant, while a comparison of group summaries at separate visits may not preserve that pairing. The registry’s description identifies time points and a summary statistic, but the analysis approach used to compare visits is not reported in the registry record.
What can a confidence interval tell readers?
General statistical context: a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval for the same kind of estimate. An interval also helps readers distinguish a point estimate from the uncertainty around it. No confidence interval for the primary outcome is reported in the registry record. The precision of any change in MMacid therefore cannot be assessed from this information.
What does the design allow?
The registry records a single-group study without masking and without a separate comparator. General statistical context: a single-group study can describe observed measurements in the participants who receive the intervention. It cannot, on its own, estimate what would have happened to those same participants over the same period under a different treatment or no study treatment. A baseline-to-follow-up difference, if reported, would be a temporal change in the observed group, not a randomized treatment contrast.
Masking can reduce the influence of expectations on some aspects of study conduct or assessment. The registry records masking as NONE. It does not describe which outcome assessments, if any, involved subjective judgment. The degree to which the absence of masking could affect particular measurements is therefore not reported in the registry record.
How should the planning illustration be read?
The registry’s planning note describes a sample-size illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used that design or that a particular effect was established. The trial is recorded as single-group, so the hypothetical equal-allocation comparison should not be mistaken for the study’s actual allocation.
General statistical context: a planning calculation estimates the sample size that would be needed for a future design under specified assumptions. It is not observed power, and it does not show that a study had a particular probability of detecting an effect after its results are known. The record does not report the sample-size illustration’s numerical outputs or the effect values on which it was based. The trial’s own sample-size justification is not reported in the registry record.
What statistical analysis is reported?
The registry lists 0 analyses. That does not identify a statistical model, adjustment strategy, hypothesis test, or approach to repeated observations. Those methods are not reported in the registry record. No p-value, adjusted estimate, treatment contrast, or uncertainty interval for the primary outcome is reported in the registry record.
The registry describes the primary outcome as applying to all randomized participants who received at least 1 dose of study drug. This is the outcome population specified in the record; the actual number analyzed and the completeness of follow-up measurements are not reported. General statistical context: the population used for an analysis affects what its estimate represents. Reporting the participants included at each visit and how missing observations were handled helps readers assess whether the analysis reflects the intended population.
General statistical context: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, uncertainty can be understated. Whether over-dispersion was considered is not reported in the registry record, and the registry entries do not identify a model to which that issue could be applied. Without reported outcome estimates and analysis details, statistical precision and model adequacy cannot be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 9 outcome measures, including the primary plasma MMacid outcome and secondary biochemical, safety, and treatment-related outcomes. It reports 0 analyses. A multiplicity plan describing how the study handled repeated statistical testing across outcomes or time points is not reported in the registry record. This means the record does not establish whether results were adjusted for multiple comparisons, whether outcomes were tested in a prespecified order, or whether some results were intended to be descriptive.
General statistical context: when many outcomes or comparisons are examined, the chance of a seemingly notable result arising by chance can increase. Prespecified priorities and a clear analysis plan help readers distinguish confirmatory tests from exploratory observations. The list of outcomes alone does not establish which statistical tests were performed or how their results should be interpreted.
The primary-outcome population is described as all randomized participants who received at least 1 dose of study drug. The actual analysis population and the number of participants contributing measurements at each visit are not reported in the registry record. The record does not explain how missing measurements were handled, whether participants discontinued, or whether analyses used imputation or only observed data. The reason for termination is also not reported in the registry record.
These omissions limit assessment of possible attrition and the completeness of the outcome data. They also prevent readers from determining whether the reported population, if any, differed from the population specified for the primary outcome. No assumptions about missing-data methods or multiplicity procedures can be made from the available information.
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 |
|---|---|---|---|
| Ataluren | 0 | 11 | 0.0% |
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 |
|---|---|
| Ataluren | 10 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ataluren |
|---|---|---|
| Vomiting | Gastrointestinal disorders | 4 of 11 |
| Nasopharyngitis | Infections and infestations | 4 of 11 |
| Glomerular vascular disorder | Renal and urinary disorders | 2 of 11 |
| Hypercreatininaemia | Renal and urinary disorders | 2 of 11 |
| Abdominal pain | Gastrointestinal disorders | 2 of 11 |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | 2 of 11 |
| Diarrhoea | Gastrointestinal disorders | 2 of 11 |
| Hypertransaminasaemia | Hepatobiliary disorders | 1 of 11 |
| Hypercalcaemia | Metabolism and nutrition disorders | 1 of 11 |
| Hypercholesterolaemia | Metabolism and nutrition disorders | 1 of 11 |
The registry reports 11 participants at risk in the ataluren group. It records 0 participants with serious adverse events and 10 participants with other adverse events. These are the registry’s participant counts; they do not provide event-level detail or establish how severe, persistent, or related to treatment the events were. The record lists no top serious adverse-event terms.
The deaths field is null. Deaths are therefore not reported in the registry record; a null entry should not be interpreted as a reported count of zero. The registry also lists planned safety outcomes concerning potentially clinically significant laboratory abnormalities and metabolic decompensation episodes, but their results are not included in the registry entries.
General statistical context: safety counts describe events recorded within a study and are most informative when considered alongside follow-up duration, event definitions, severity, and attribution. Those details are not reported in the registry record. The single-group design also provides no concurrent comparison for interpreting how the recorded adverse events compare with another treatment or with no study treatment. These figures describe the registry’s reported safety counts and do not, by themselves, establish cause or comparative risk.
12. What the Result Does, and Does Not, Mean
This record describes a Phase 2 study of oral ataluren in participants with MMA due to a nonsense mutation. Its primary outcome was plasma MMacid, measured at baseline and at specified end-of-dosing visits. The registry also identifies safety and other biochemical outcomes. These details establish what the study set out to assess, but they do not reveal the primary outcome results: the observed MMacid values are not reported in the registry record.
The record does not establish whether plasma MMacid decreased, increased, or remained stable. It provides no estimated change, confidence interval, or reported statistical test for that outcome. The study’s stated purpose was to understand whether ataluren could safely decrease MMacid levels, but a stated purpose is not an observed result.
The single-group design also limits what any within-group change could establish. General statistical context: without a concurrent comparator, changes over time cannot be separated from other influences with the same confidence as a randomized treatment contrast. A laboratory outcome can describe a measured biochemical change, but it does not by itself show a change in symptoms or other clinical outcomes.
The registry records 0 participants with serious adverse events and 10 with other adverse events among 11 at risk in the ataluren group. These counts do not establish whether an event was caused by ataluren, and the record does not provide detailed event descriptions. The reason for the TERMINATED status is not reported in the registry record.
Accordingly, the record supports a description of the study’s population, intervention, design, outcome schedule, and recorded adverse-event counts. It does not support a conclusion about the size or precision of a treatment effect, a comparison with another treatment, or the overall clinical meaning of the study’s results.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a study question and a reported result. The registry identifies a biologically relevant laboratory outcome, a measurement method, and repeated measurement times. Those details help define what the study intended to observe. However, without the actual endpoint values, the direction and magnitude of the observed pattern cannot be assessed.
The single-group design is also central to interpretation. A sequence of measurements in participants receiving ataluren could describe change during the study, but it would not provide a concurrent treatment contrast. General statistical context: the design determines which comparisons can be made, regardless of how carefully an outcome is measured. Here, the record describes no separate control group.
The use of a median and full range makes clear that the planned summary focused on the distribution of plasma MMacid rather than only a mean. General statistical context: this can be useful when values are skewed or when extreme values are important to describe. But the statistic alone cannot convey precision, and the observed summaries are not reported in the registry record.
The record also illustrates why analysis details matter. It lists 9 outcome measures and 0 analyses, while multiplicity procedures, missing-data handling, and the detailed statistical plan are not reported in the registry record. Readers cannot determine how comparisons were prioritized or how incomplete measurements were treated.
Finally, the safety counts have to be read in context: the registry records 0 serious adverse events and 10 participants with other adverse events, but does not report detailed event descriptions or deaths. These registry entries describe the available record, not a comparative safety estimate. Taken together, the study design and reporting identify important questions but leave the principal outcome and its uncertainty unresolved.
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 primary limitation for interpreting efficacy is that the registry record does not report the observed plasma MMacid values. Although it specifies the outcome, summary statistic, measurement method, and assessment schedule, no medians, ranges, changes, or uncertainty estimates are available in the registry record. The magnitude and precision of any biochemical response therefore cannot be assessed.
The study is recorded as single-group, with allocation NA and masking NONE. No concurrent control group is described. Any change from baseline would consequently be difficult to distinguish from changes over time or other influences. The record does not report a treatment comparison.
The study status is TERMINATED, but the reason for termination is not reported in the registry record. The enrollment is 11, and the outcome population is defined as all randomized participants who received at least 1 dose. The number included in each analysis, follow-up completeness, and handling of missing measurements are not reported. The registry’s primary-outcome population wording does not provide the actual analysis count.
The intervention description is incomplete for Cycle 2. The analysis plan, sample-size justification, multiplicity procedures, and statistical methods are not reported in the registry record. The record lists 9 outcome measures but reports 0 analyses, limiting assessment of the intended comparisons and their interpretation.
Safety information is also limited: the record gives participant counts for serious and other adverse events but does not provide detailed terms for the other events, and deaths are not reported in the registry record. These limitations restrict both efficacy and safety interpretation; they do not establish that a particular result occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ataluren for Nonsense Mutation Methylmalonic Acidemia — NCT01141075.
- Registry record last updated 2020-07-07; status last verified 2020-06.
- Results first posted 2020-07-07.
- 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
NCT01141075 is a Phase 2 study titled Ataluren for Nonsense Mutation Methylmalonic Acidemia. It evaluated oral ataluren in a single-group design for participants with MMA due to a nonsense mutation. Allocation is recorded as NA and masking as NONE. Enrollment was 11. The study status is TERMINATED; its reason for termination is not reported in the registry record.
The primary outcome was plasma MMacid, summarized by median and full range at baseline and at Day 28 and Day 29, the last day of dosing, in Cycles 1 and 2. The observed primary-outcome values and the listed secondary-outcome results are not reported in the registry record. The record reports 0 participants with serious adverse events and 10 with other adverse events among 11 at risk in the ataluren group; deaths are not reported in the registry record.
The single-group design does not provide a concurrent treatment comparison. Missing-data handling, multiplicity procedures, and the detailed statistical analysis plan are not reported in the registry record.