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 Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (NCT02367014), a randomized phase 1, phase 2 study. The primary outcome is Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02367014 |
| Phase | Phase 1, Phase 2 |
| Condition | Mitochondrial Myopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 36 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Stealth BioTherapeutics Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had mitochondrial myopathy associated with genetically confirmed mitochondrial disease. The registry record describes a multicenter study and reports enrollment of 36 participants. The primary endpoint results are reported for four groups, each with 9 participants.
Intervention
Participants received intravenous elamipretide, also called MTP-131 in the study title, at one of three dose levels. The low dose was 0.01 mg/kg/hr, the intermediate dose was 0.10 mg/kg/hr, and the high dose was 0.25 mg/kg/hr. Each infusion was given over 2 hours for 5 days.
Comparator
The comparator was matching placebo, administered once daily over 2 hours for 5 days. The registry describes a randomized, double-blind, placebo-controlled study with parallel groups and multiple ascending doses. The masking field records quadruple masking; which specific roles were masked is not reported in the registry record.
Primary question
The primary endpoint asked how far participants walked on the six-minute walk test at Day 5 compared with baseline. The registry reports a least-squares mean change for each dose group and placebo, along with a full range for each estimate. These group-level summaries describe the observed endpoint results; the registry does not report a direct treatment-versus-placebo contrast or its inferential statistics.
3. Trial Design
This was a phase 1/2 randomized, double-blind, placebo-controlled, parallel-group study of intravenous MTP-131, or elamipretide, for mitochondrial myopathy. It used multiple ascending doses and enrolled participants with mitochondrial myopathy associated with genetically confirmed mitochondrial disease. The registry describes the study as multicenter. The study status is completed; the recorded start was 2015-02 and primary completion was 2016-04.
The registry reports enrollment of 36 participants. The primary results are presented for four groups, each with 9 participants: low-dose elamipretide, intermediate-dose elamipretide, high-dose elamipretide, and placebo. The active dose regimens were 0.01 mg/kg/hr, 0.10 mg/kg/hr, and 0.25 mg/kg/hr, respectively. Each was infused over 2 hours for 5 days. In each cohort, participants received either intravenous elamipretide once daily for 2 hours for 5 days or matching placebo.
The primary endpoint was change in distance walked on the six-minute walk test, measured from baseline to Day 5, the end-of-treatment visit. The study also listed outcomes covering exercise capacity, ventilation, oxygen use, and lactate. The registry describes safety, tolerability, pharmacokinetics, and preliminary efficacy as study aims. Details such as the randomization procedure, allocation concealment, the exact roles masked, and the statistical analysis plan 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.
Overall Study
| Stage | Low Dose | Intermediate Dose | High Dose | Placebo |
|---|---|---|---|---|
| STARTED | 9 | 9 | 9 | 9 |
| COMPLETED | 9 | 9 | 9 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
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 | Low Dose | Intermediate Dose | High Dose | Placebo | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 9 | 9 | 9 | 9 | 36 | |
| Age, Continuous | years | 40.8 (SD 11.32) | 45.0 (SD 14.09) | 42.3 (SD 16.84) | 41.9 (SD 15.83) | 42.5 (SD 14.12) |
| Sex: Female, Male: Female | Participants | 7 | 8 | 6 | 9 | 30 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 | 0 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT), measured over Assessed at Baseline, Day 5 (end-of-treatment visit).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Full Range |
| Unit | meters |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in distance walked, in meters, on the six-minute walk test from baseline to Day 5. Baseline is described as the last assessment before the study began, and Day 5 is the end-of-treatment visit. A positive change indicates a greater distance at the Day 5 assessment than at baseline; a negative change indicates a shorter distance. This describes the direction of the endpoint, not whether a treatment caused a change.
As a general measurement concept, a timed walking test captures a participant’s ability to cover distance during a standardized period of activity. It can therefore provide a functional measure that complements laboratory or physiological measures. The registry lists other outcomes related to oxygen uptake, ventilatory efficiency, aerobic efficiency, oxygen utilization, oxygen uptake kinetics, and lactate levels.
The reported endpoint statistic is a least-squares mean change, accompanied by a full range. The registry does not give the model used to obtain the least-squares means or define further details of endpoint collection. A full range describes the reported lower and upper values; it is not, by itself, a confidence interval or a measure of precision for a treatment-versus-placebo effect. The registry record does not report a direct contrast between groups for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported least-squares mean changes in six-minute walk distance were 13.5 meters for low-dose elamipretide, 36.5 meters for intermediate-dose elamipretide, 64.5 meters for high-dose elamipretide, and 20.4 meters for placebo. Each group had 9 participants in the primary results. These are group-level changes from baseline to Day 5, not estimates of the difference between an elamipretide dose and placebo.
The registry reports full ranges of -72.0 to 86.0 meters for the low-dose group, -20.0 to 107.0 meters for the intermediate-dose group, 4.0 to 133.0 meters for the high-dose group, and -37.0 to 90.0 meters for placebo. The reported ranges for low dose, intermediate dose, and placebo extend across zero; the reported high-dose range is above zero. These descriptions characterize the ranges as recorded, but do not establish the statistical significance of a group’s change or of a comparison between groups.
The largest posted group mean is for high-dose elamipretide. That ordering alone does not show that the high dose performed better than placebo: a dose-versus-placebo comparison requires a defined contrast and an estimate of its uncertainty. The registry record does not report a treatment-versus-placebo estimate, confidence interval, or p-value for the primary endpoint. It also does not report an adjusted or unadjusted inferential analysis for this outcome. No direct efficacy conclusion can be drawn from the group means and ranges alone.
There is no stated standard error or confidence interval around the least-squares means. The ranges are identified as full ranges, so they should not be interpreted as confidence intervals. A full range records the span represented by its endpoints, while a confidence interval is an inferential summary of uncertainty about an estimated quantity. Without the underlying observations and analysis details, the precision of the group means and the uncertainty in treatment contrasts cannot be determined from these summaries.
The result is also limited to the short assessment period: baseline to Day 5, at the end of the 5-day treatment regimen. It does not describe persistence after treatment or longer-term functional outcomes. The registry presents the study as an early-phase evaluation of safety, tolerability, pharmacokinetics, and preliminary efficacy. The primary endpoint summaries are therefore best read as descriptive results from this trial, rather than as a definitive estimate of comparative treatment effect.
9. Statistical Methods Explained
The posted primary endpoint is a change score: each participant’s distance at Day 5 is considered relative to that participant’s baseline distance, and the group result is summarized as a least-squares mean. The registry identifies the statistic as a least-squares mean and reports a full range for each group. It does not report the statistical model, any covariates, assumptions, or the method used to account for incomplete measurements. Those details are not reported in the registry record.
What does a least-squares mean represent?
As a general statistical concept, a least-squares mean is an estimated group mean derived from a fitted model. Depending on the model, it may represent a mean adjusted for other terms included in that model. The registry does not identify which terms, if any, were included in this study’s model. The reported values should therefore be described as least-squares means, without assuming a particular adjustment or model structure.
A group mean change and a treatment effect are different quantities. The mean change describes the group’s endpoint relative to its own baseline. A treatment effect for this randomized comparison would ordinarily be expressed through a defined contrast between an elamipretide group and placebo, with an uncertainty estimate. The registry reports the group summaries but no such contrast for the primary outcome. It is not appropriate to derive one from the posted means, since doing so would add a calculation not reported in the registry record and would not supply its uncertainty or analysis context.
How should the full ranges be read?
The registry labels the dispersion as a full range. In general, a range gives lower and upper values for the observations or summary represented; it does not quantify uncertainty in the same way as a confidence interval. A range can be strongly affected by extreme values, particularly when a group is small. It does not show the distribution of values within the endpoints, the standard error of the mean, or whether differences between groups are compatible with chance variation.
A confidence interval, in general, is a range constructed by an inferential procedure to describe uncertainty around an estimate. It is not interchangeable with a full range. No confidence intervals for the least-squares means or for treatment-versus-placebo effects are reported in the registry record. The ranges should therefore be interpreted literally as the stated dispersion measure, rather than as evidence of statistical significance or nonsignificance.
Why is a direct contrast important?
Randomization supports a comparison between assigned groups, but the comparison still needs to be specified and analyzed. A contrast states which groups are being compared and how their outcomes are combined. For example, a dose-versus-placebo contrast would answer a different question from a comparison among all dose groups. An estimate and uncertainty measure for that contrast are needed to judge how precisely the data distinguish the groups. The registry record does not report the primary-endpoint contrasts, their confidence intervals, or p-values.
There are several active dose groups and multiple listed outcomes. As a general statistical issue, examining many possible comparisons or outcomes increases the chance of an apparently notable result arising by chance if no adjustment or prespecified testing strategy is used. The registry’s multiplicity strategy and prespecified hierarchy are not reported in the registry record. This means it is not possible to tell from the record how the investigators planned to control error across tests, or which results were intended to be confirmatory rather than exploratory.
What do the sample-size illustrations mean?
The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider detecting a stated fraction of the observed effect. These are planning scenarios based on the observed effect, not observed power and not a description of the trial’s original design calculation. The original sample-size justification is not reported in the registry record. The illustrations do not establish that the trial was designed to detect a particular effect or that its results have a particular probability of being correct.
The registry describes this as a phase 1/2 study with safety, tolerability, pharmacokinetic, and preliminary efficacy aims. The statistical analysis plan, including model specifications, handling of repeated measurements, treatment of missing values, and methods for any interim analyses, is not reported in the registry record. No interim analyses are reported in the registry record. Without those details, the posted endpoint summaries can be described, but their analytic derivation cannot be fully reconstructed.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 27 secondary outcomes and reports 28 outcome measures. These include measures of oxygen uptake, ventilatory and aerobic efficiency, oxygen utilization, oxygen uptake kinetics, and pre-exercise and post-exercise lactate, among others. With multiple outcomes and three active dose groups, the interpretation of any collection of tests depends on the planned testing strategy. The registry’s multiplicity adjustment, outcome hierarchy, and distinction between confirmatory and exploratory analyses are not reported in the registry record. The registry record lists no analysis entries for the reported outcomes.
Details on missing data are not reported in the registry record. It does not state whether any primary endpoint measurements were missing, how missing measurements were handled, or which analysis population was used. The record’s reported group sizes do not establish whether every randomized participant contributed an evaluable baseline and Day 5 measurement, nor do they identify an intention-to-treat, per-protocol, or other analysis population.
These omissions matter because the treatment contrast and its uncertainty can depend on the analysis population, the handling of incomplete data, and any adjustment for multiple comparisons. Without those details, the posted group summaries cannot establish whether a particular missing-data assumption or multiplicity procedure was used. The record does not report interim analyses or the statistical plan for the primary endpoint.
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 |
|---|---|---|---|
| Low Dose | 0 | 9 | 0.0% |
| Intermediate Dose | 0 | 9 | 0.0% |
| High Dose | 0 | 9 | 0.0% |
| Placebo | 0 | 9 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Low Dose | 0 of 9 |
| Intermediate Dose | 0 of 9 |
| High Dose | 0 of 9 |
| Placebo | 0 of 9 |
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 |
|---|---|
| Low Dose | 7 of 9 |
| Intermediate Dose | 7 of 9 |
| High Dose | 5 of 9 |
| Placebo | 5 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Low Dose | Intermediate Dose | High Dose | Placebo |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 1 of 9 | 1 of 9 | 2 of 9 | 2 of 9 |
| Dizziness | Nervous system disorders | 2 of 9 | 1 of 9 | 0 of 9 | 0 of 9 |
| Abdominal pain | Gastrointestinal disorders | 0 of 9 | 2 of 9 | 0 of 9 | 0 of 9 |
| Flatulence | Gastrointestinal disorders | 1 of 9 | 0 of 9 | 0 of 9 | 1 of 9 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 1 of 9 | 0 of 9 | 0 of 9 | 1 of 9 |
| Increased appetite | Metabolism and nutrition disorders | 1 of 9 | 0 of 9 | 0 of 9 | 1 of 9 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 9 | 1 of 9 | 1 of 9 | 0 of 9 |
| Constipation | Gastrointestinal disorders | 0 of 9 | 0 of 9 | 0 of 9 | 1 of 9 |
| Nausea | Gastrointestinal disorders | 0 of 9 | 1 of 9 | 0 of 9 | 0 of 9 |
| Injection site bruising | General disorders | 1 of 9 | 0 of 9 | 0 of 9 | 0 of 9 |
The registry reports serious adverse events by group. For low-dose elamipretide, 0 of 9 participants at risk had a serious adverse event; the same figures are reported for intermediate dose, high dose, and placebo. Deaths are reported as 0 in each group. No serious adverse event terms are listed in the record.
These are observed counts during the trial’s reported safety assessment, not proof that serious events cannot occur. With 9 participants at risk in each group, the counts provide limited information about uncommon events, and the record does not provide a comparative statistical analysis of serious adverse events. The serious-event figures should not be used to claim that the groups have equivalent safety profiles.
The record also reports other adverse events affecting 7 participants in the low-dose group, 7 in the intermediate-dose group, 5 in the high-dose group, and 5 in the placebo group; 9 participants were at risk in each group. These counts are separate from the serious adverse event counts as presented in the record. The registry does not provide event-level detail for these other adverse events in the information, so their type, severity, timing, and relationship to treatment cannot be assessed from these counts alone.
12. What the Result Does, and Does Not, Mean
The primary endpoint summaries describe change in six-minute walk distance from baseline to the end of the 5-day treatment period. The reported least-squares mean changes are 13.5 meters for low dose, 36.5 meters for intermediate dose, 64.5 meters for high dose, and 20.4 meters for placebo. The full ranges are also reported for each group. These statistics describe the groups as recorded; they do not, on their own, estimate the effect of elamipretide compared with placebo.
The result does not establish that one dose differs from placebo. A comparative conclusion would require a treatment contrast and an uncertainty measure, neither of which is reported for the primary endpoint in the registry record. The group mean ordering is not a substitute for that analysis. Nor do the ranges serve as confidence intervals or as a formal test of a treatment effect.
The endpoint addresses a functional measure at Day 5. It does not, by itself, establish whether any change persists beyond the end of treatment or whether it corresponds to changes in the other listed physiological outcomes. The registry record does not report longer-term primary endpoint results. The study’s broader aims included safety, tolerability, pharmacokinetics, and preliminary efficacy, but the available primary endpoint summaries do not answer all of those questions.
As a general principle, a randomized, placebo-controlled design can support a fair comparison when the analysis appropriately preserves the randomized groups and accounts for uncertainty. The record identifies the randomized design but does not include enough analysis detail to evaluate the primary treatment contrast. Its completed status indicates that the study is recorded as completed; it does not by itself establish the strength or certainty of a result.
The most defensible reading is therefore descriptive: the registry reports group-level changes and full ranges for a short-term walking outcome, alongside safety counts. The evidence displayed in these summaries should not be treated as a definitive demonstration of comparative efficacy or as proof of an absence of safety concerns.
13. Why This Trial Matters Statistically
This study illustrates why the reported form of a result matters as much as the numerical estimate. A least-squares mean change summarizes a group’s movement from baseline, but a randomized treatment question asks how outcomes compare between assigned groups. Without a reported contrast and its uncertainty, the group summaries cannot quantify the comparative effect that readers may want to assess.
The trial also highlights the distinction between a full range and an inferential interval. The registry reports full ranges, which convey the span of the reported values but do not directly quantify uncertainty around a mean or treatment effect. Readers need to know which kind of spread is reported before making claims about precision or statistical significance.
Multiple active doses and many secondary outcomes create a further interpretive issue. As a general matter, multiple testing can make isolated results difficult to evaluate unless the analysis plan specifies priorities and how error across tests will be addressed. The registry record does not report that plan. This is particularly relevant in a phase 1/2 study whose stated aims include preliminary efficacy alongside safety and pharmacokinetics.
The reported safety counts also show why zero observed serious events should be interpreted cautiously in small groups. Counts are useful descriptions of what was observed, but they do not establish that serious events are impossible or that safety is the same across groups. Overall, the record gives concrete short-term endpoint and adverse-event summaries while leaving important inferential and analysis details unreported.
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 endpoint results are presented as least-squares mean changes with full ranges, but no treatment-versus-placebo contrast, confidence interval, or p-value is reported in the registry record. The ranges are not confidence intervals, and the model used to calculate the least-squares means is not described. These omissions limit assessment of comparative effect and statistical precision.
Each primary results group has 9 participants, limiting how much the summaries can show about variability and uncommon outcomes. The treatment period lasted 5 days, and the primary endpoint was assessed at Day 5. Longer-term outcome results are not reported in the registry record. The study population was defined by mitochondrial myopathy associated with genetically confirmed mitochondrial disease; the record does not provide further participant characteristics needed to assess how closely these results apply to other populations.
The registry does not report the analysis population, missing-data handling, model specifications, multiplicity strategy, or original sample-size justification. It also does not report interim analyses. The adverse-event summaries provide counts but do not provide event-level detail for other adverse events, and no serious adverse event terms are listed. These gaps limit evaluation of the completeness of endpoint analyses, the role of multiple testing, and the interpretation of safety patterns.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy — NCT02367014.
- Registry record last updated 2019-12-27; status last verified 2019-12.
- Results first posted 2019-12-27.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02367014 is a completed phase 1/2 randomized, double-blind, placebo-controlled, parallel-group study of intravenous MTP-131, or elamipretide, for mitochondrial myopathy associated with genetically confirmed mitochondrial disease. The registry describes multiple ascending doses and reports enrollment of 36 participants. The active regimens were 0.01 mg/kg/hr, 0.10 mg/kg/hr, and 0.25 mg/kg/hr, infused over 2 hours for 5 days; the comparator was matching placebo.
The primary endpoint was change in six-minute walk distance from baseline to Day 5. The registry reports least-squares mean changes of 13.5 meters, 36.5 meters, 64.5 meters, and 20.4 meters for low dose, intermediate dose, high dose, and placebo, respectively, with full ranges. It does not report a primary treatment-versus-placebo contrast or its uncertainty. Serious adverse events and deaths are reported as 0 in each group. Analysis-plan details, missing-data handling, and multiplicity procedures are not reported in the registry record.