A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly (NCT02245620), a randomized phase 2 study. The primary outcome is Change From Baseline in ATPmax (Maximal ATP Synthetic Rate).

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, placebo-controlled study with a parallel-group model. The registry record reports enrollment of 41 participants and lists Elamipretide and Placebo as the two interventions. Its masking designation is quadruple. The record does not explain which roles were masked, so more specific claims about who remained unaware of assignment are not warranted.

The study addressed skeletal muscle mitochondrial dysfunction in elderly participants. Its brief summary says that participants had previous evidence of mitochondrial dysfunction. The registry record does not specify an age cutoff or provide further eligibility criteria in the information available for this summary.

Participants assigned to elamipretide received a single intravenous infusion at 0.25 mg/kg/hr, delivered at 60 mL/hr for 2 hours. The placebo infusion was also given at 60 mL/hr for 2 hours and contained lyophilized excipients without elamipretide. The parallel design means the two assigned groups were followed as separate groups rather than crossing over between interventions.

The listed primary outcome was change from baseline in ATPmax. The measurement schedule included baseline, Day 1 Hour 2—described as 2 hours after infusion began or the end of infusion—and Day 7. Secondary outcomes included mean change from baseline in the phosphate/oxygen ratio, nicotine adenine dinucleotide, and muscle force-time-integral. The record lists four outcome measures overall but reports no analysis entries. Detailed randomization procedures, the planned statistical model, and the rationale for the enrollment target 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.

Before assignment: 2 subjects discontinued prematurely as per Investigator's discretion. These 2 subjects (Subject 001019 \[Elamipretide group\] and Subject 001063 \[Placebo group\]) were discontinued after randomization but prior to receiving study treatment; both were not treated due to their pre-infusion sodium levels meeting Exclusion Criteria 6.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants for whom Maximal ATP synthetic rate was measured at baseline and Day 1 Hour 2, and Day 7

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.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in ATPmax (Maximal ATP Synthetic Rate), measured over From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7.

ATPmax is the maximal ATP synthetic rate, expressed in mM/sec. The registry record describes it as phosphorylation capacity per unit muscle volume, determined using a muscle fatigue test. It is a continuous measure: each recorded value can take a range of numeric values rather than representing an event such as hospitalization or death.

The primary outcome concerns change from baseline at the post-infusion assessment and at Day 7. Measuring change can describe how a participant’s ATPmax differs from their own baseline, while a comparison between randomized groups can address whether the recorded changes differ between assigned interventions. Those are distinct questions: a change within one group alone does not establish a difference between groups.

ATPmax was selected as a measure of skeletal muscle energy production capacity, a process relevant to the study’s focus on mitochondrial dysfunction. This is a general explanation of why a continuous physiological measure may be used as an endpoint; the registry record does not state the full endpoint-selection rationale or establish how strongly ATPmax represents broader muscle function.

The record describes multiple assessment times and says the outcome population consisted of participants with ATPmax measured at baseline, Day 1 Hour 2, and Day 7. It does not give the reported group means, standard deviations, estimated changes, uncertainty intervals, or a test of the between-group contrast. Consequently, the endpoint definition can be explained, but the magnitude and precision of the outcome cannot be interpreted from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, and the registry record identifies the outcome parameter as a mean with standard deviation as its dispersion measure. That describes a way to summarize measurements: the mean represents the average, while the standard deviation describes how spread out participant measurements are around that average. It does not identify the statistical test or model used to compare groups. The planned analysis method is not reported in the registry record.

What does a change-from-baseline outcome represent?

In general, change from baseline is calculated for each participant by comparing a follow-up measurement with that participant’s baseline measurement. Group summaries can then describe the average change among participants with usable measurements. A treatment comparison generally requires a contrast between the assigned groups, rather than interpreting change in one group alone. The registry record names changes from baseline at Day 1 Hour 2 and Day 7 but does not report the group-level changes or the between-group estimates.

There are different ways to analyze repeated measurements. A model may compare groups at a specified time, account for baseline values, or use measurements across multiple times together. These approaches can rely on different assumptions and can answer somewhat different questions. This is general statistical context, not a description of the method used in this study: the registry record does not identify a model, covariate adjustment, or method for handling repeated measurements.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the analysis at a stated confidence level. Its width conveys precision: wider intervals indicate greater uncertainty than narrower intervals. A p-value, when reported, summarizes how compatible the observed data are with a specified null hypothesis under the statistical model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for ATPmax is reported in the registry record, so neither can be interpreted for this study from the recorded information.

For continuous outcomes, a standard deviation describes variability among measurements, whereas a standard error describes uncertainty in an estimated mean. They are not interchangeable. The registry record identifies standard deviation as the dispersion measure for the primary outcome, but gives no numerical standard deviation or standard error. It also does not report the distribution of ATPmax values or whether assumptions for any particular statistical test were checked.

Why can over-dispersion matter?

In general, over-dispersion means that the observed variability is greater than a statistical model assumes. When a model underestimates variability, its uncertainty estimates may be too small and its intervals too narrow. Over-dispersion is especially discussed for count outcomes, where the variability may exceed what a simple count model expects. ATPmax is a continuous measure, and the registry record does not report a model or a dispersion assessment. This general concept should not be taken to mean that over-dispersion occurred in this trial.

What do planning illustrations mean?

In general, sample-size planning asks how many participants would be needed under stated assumptions about an effect, variability, allocation, and statistical error rates. The registry record describes planning illustrations based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are hypothetical planning calculations, not observed trial outcomes and not observed power. Their assumptions do not show that the original study was designed using those calculations.

A planning calculation based on an observed effect is sensitive to that effect estimate. If the estimate is uncertain, the resulting planning illustration is uncertain as well. Considering a fraction of an effect can illustrate how the required sample size changes when a smaller effect is targeted, but it does not establish which effect would be important or likely in another study. The registry record does not report the study’s own sample-size justification, so the planning assumptions should not be mistaken for the original design rationale.

Random allocation can support a fair comparison by reducing systematic differences in expectation between assigned groups, but it does not guarantee identical groups, especially in a modest-sized study. Masking can reduce some forms of bias, though the registry designation alone does not explain the practical masking procedures. These are general design principles. The registry record does not describe the randomization sequence, allocation concealment, or masking procedures in detail.

Because the primary outcome has multiple listed assessment times, interpretation depends on which time-specific contrast is considered and how those comparisons were planned. The registry record does not describe a statistical analysis plan, a prespecified hierarchy, or adjustment for multiple comparisons. The record also contains no analysis entries. Therefore, no specific test, adjustment, or model should be attributed to the investigators on the basis of the recorded information.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described at baseline, Day 1 Hour 2, and Day 7. In addition, the record lists secondary outcomes for phosphate/oxygen ratio, nicotine adenine dinucleotide, and muscle force-time-integral. Considering multiple outcomes or assessment times raises the general issue of multiplicity: the more comparisons examined, the greater the chance that at least one may appear notable by chance if each is treated as a separate test.

Statistical plans can address multiplicity in different ways, including identifying a primary comparison in advance, setting an order for interpreting outcomes, or adjusting significance thresholds. The registry record does not state whether any such approach was planned or used. It does not describe interim analyses or a testing hierarchy. These details are not reported in the registry record and should not be inferred from the outcome list.

The record defines the primary outcome population as participants with measurements at baseline, Day 1 Hour 2, and Day 7. This identifies a measurement-based population, but it does not explain how many participants had complete observations at each time or how missing measurements were handled. The method for missing data, if any, is not reported in the registry record.

The record also does not specify whether the primary analysis used all randomized participants, only participants with available measurements, or another analysis population. Enrollment alone does not resolve that question. Without participant flow and analysis details, the effect of missing outcome data on the estimated comparison cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious adverse events separately from other adverse events and deaths. In the elamipretide group, 19 participants were at risk for serious events and 19 for other events; zero serious events and three other adverse events were reported. In the placebo group, 20 participants were at risk for serious events and 20 for other events; zero serious events and two other adverse events were reported. No deaths were reported in either group.

These are counts, not rates, and the record does not provide event descriptions, severity details beyond the serious-event category, timing, or participant-level information. It also does not report a statistical comparison of adverse events. The listed counts therefore describe what was recorded, but cannot establish whether the groups differed in risk.

Zero reported serious events means none were recorded in these group entries; it does not demonstrate that serious events are impossible or that a treatment has no safety risks. General interpretation of safety counts depends on the number followed, duration and completeness of follow-up, event definitions, and how events were collected. Those details are not reported in the registry record. The figures should be read as descriptive registry entries, not as a comprehensive safety assessment or a basis for medical advice.

12. What the Result Does, and Does Not, Mean

The record establishes that a randomized, double-blind, placebo-controlled Phase 2 study evaluated a single intravenous dose of elamipretide in elderly participants with previous evidence of mitochondrial dysfunction. It specifies ATPmax change from baseline as the primary outcome and describes measurement at baseline, Day 1 Hour 2, and Day 7. It also identifies additional muscle energetics and performance outcomes.

Those design details explain the question the study set out to examine. They do not supply an answer to that question. Numerical results for ATPmax and the secondary outcomes are not reported in the registry record, and no analysis entries are listed. The record therefore does not establish the size, direction, or precision of a treatment-group difference. It also does not show that the groups were equivalent.

Even when a trial reports a measured difference, statistical interpretation requires attention to uncertainty, the chosen analysis population, missing data, and the exact comparison being made. Here, the details needed to assess those features are absent. The study’s enrollment and design cannot substitute for outcome estimates, and its stated objective cannot be treated as evidence of an effect.

The safety entries report zero serious adverse events and zero deaths in both groups, with three other adverse events recorded for elamipretide and two for placebo. These counts are descriptive and do not establish a comparative safety conclusion. The registry record does not give the event details or analysis needed for a fuller assessment.

Accordingly, the appropriate reading is narrow: the registry record documents a clinical study design, intervention regimens, outcome definitions, and limited adverse-event counts, while leaving key results and analysis details unreported. It does not support a conclusion about whether elamipretide changed ATPmax or whether any observed change was precise or meaningful.

13. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the distinction between a registered research question and a reported result. A randomized design can be informative only when the outcome estimates and their uncertainty are available for interpretation. In this registry record, the intervention, comparator, endpoint, assessment schedule, and broad design are described, but the primary numerical comparison is not.

The endpoint also shows why outcome definition matters. ATPmax is a continuous measure of maximal ATP synthetic rate, assessed at more than one follow-up time. A result needs to identify the time point and the contrast being estimated; a change within a group is not the same as a difference between groups. Without the estimates and analysis details, readers cannot determine which interpretation would apply.

The record’s outcome list raises general questions about how several outcomes and time points are handled. A prespecified analysis strategy helps readers distinguish primary conclusions from exploratory comparisons and understand how multiplicity was considered. No such strategy is described in the registry record. The absence of that information does not show that no plan existed, but it means the plan cannot be evaluated from this record.

Finally, the safety entries demonstrate the limits of small descriptive counts. Counts of serious and other adverse events are useful information, but their interpretation depends on follow-up, event definitions, and complete reporting. The record does not include enough detail to support a comparative safety analysis. These limitations make transparent reporting of estimates, uncertainty, analysis populations, and missing-data handling especially important for interpreting a 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 main limitation for statistical interpretation is that the registry record does not report numerical results for the primary ATPmax outcome. It gives no group-specific changes, between-group estimate, uncertainty interval, or p-value. As a result, the observed effect and its precision cannot be assessed.

The assessment schedule includes Day 1 Hour 2 and Day 7, but the record does not provide separate estimates for those time points or explain which comparison was intended to carry the primary interpretation. It lists secondary outcomes but provides no numerical findings for them. No analysis entries are reported.

Important design and analysis details are also absent. The statistical model, test, covariate adjustment, handling of repeated measurements, multiplicity approach, missing-data method, and analysis population beyond the measurement-based description are not reported in the registry record. The participant flow and the numbers with usable observations at each assessment are not given. The record also does not describe the randomization procedure or masking procedures in detail.

The safety information is limited to group counts. It does not identify the events, their timing, or the methods used to collect them, and it reports no comparative safety analysis. The enrollment count and the safety group counts do not by themselves describe endpoint completion or follow-up completeness.

Finally, the registry record does not report the study’s sample-size justification. Planning illustrations based on an observed effect are not a substitute for that rationale and are not observed power. These gaps constrain interpretation of the record; they do not establish that the study lacked a protocol or that unreported procedures were not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly — NCT02245620.
• Registry record last updated 2020-06-23; status last verified 2020-06.
• Results first posted 2020-06-23.
• 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.

18. Record Summary

NCT02245620 is a completed Phase 2 randomized, double-blind, placebo-controlled, parallel-group study sponsored by Stealth BioTherapeutics Inc. It enrolled 41 elderly participants with previous evidence of mitochondrial dysfunction. The elamipretide group received a single intravenous infusion of 0.25 mg/kg/hr at 60 mL/hr for 2 hours; the placebo group received an infusion at 60 mL/hr for 2 hours.

The primary outcome was change from baseline in ATPmax, measured at baseline, Day 1 Hour 2, and Day 7. Secondary outcomes addressed phosphate/oxygen ratio, nicotine adenine dinucleotide, and muscle force-time-integral. Numerical outcome results and analysis entries are not reported in the registry record. The safety entries list zero serious adverse events and zero deaths in each group, with three other adverse events in the elamipretide group and two in the placebo group.