A Double-blind, Placebo-controlled, Randomized INTerventional Clinical Trial (SARA-INT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Double-blind, Placebo-controlled, Randomized INTerventional Clinical Trial (SARA-INT) (NCT03452488), a randomized phase 2 study. The primary outcome is Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test.

2. Clinical Question

3. Trial Design

SARA-INT was a phase 2, randomized, double-blind, parallel-group clinical trial sponsored by Biophytis. The registry records enrollment of 233 participants. The trial is marked completed, with a start date of 2017-02-07 and a primary completion date of 2020-04-26. These administrative details describe the registry record and do not establish how complete the outcome data were.

The three treatment groups were placebo, 175 mg BIO101, and 350 mg BIO101. Each regimen was taken orally twice daily, 12 hours apart. Although the intended treatment duration was 6 months, the registry says that treatment was extended up to 9 months for some participants because of the COVID pandemic. The primary outcome timeframe remained baseline to 6 months; the endpoint description says data up to 9 months were used for some pandemic-era participants when 6-month data were unavailable.

The registry describes the primary outcome as change from baseline to 6 months in gait speed for the 400-meter walking test, reported as a least-squares mean with a 95% confidence interval. It also lists secondary measures including physical function, handgrip and knee-extension strength, lean body mass, chair stands, walking distance, response on the 400-meter test, and disability assessment for obese participants.

The record notes that >50% of endpoint data were missing because of the pandemic and that this may have affected the study's ability to deliver expected results. The numerical primary outcome results, allocation details beyond randomization, and full statistical 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: The Full Analysis Set (FAS) population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included. One participant randomized but not treated with 175 mg BIO101.

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: One participant randomized but not treated with 175 mg BIO101.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test, measured over Baseline and 6 Months.

The primary endpoint was change from baseline to 6 months in gait speed on the 400-meter walking test. The test measures the time taken to walk 400 meters; gait speed is expressed in meters per second. The endpoint therefore represents change in a continuous measure of walking performance rather than a count of events or a yes-or-no outcome.

Walking speed is used in this trial as a measure of mobility function in participants with age-related sarcopenia who were considered at risk of mobility disability. The 400-meter distance provides a sustained walking task, and the endpoint focuses on change from each participant's baseline rather than only the value at follow-up. In general, a change-from-baseline measure can describe how an outcome shifts over time, while a between-group comparison asks whether that change differs across assigned treatments.

The registry reports the endpoint as a least-squares mean with a 95% confidence interval. The endpoint description also states that missing values were addressed using adjusted Bayesian multiple imputation for non-completers who failed test feasibility and multiple imputation for participants without on-site visit data. For participants enrolled during the COVID-19 pandemic, data up to 9 months could be used when 6-month data were unavailable. Numerical estimates for the treatment groups and their comparisons are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: gait speed is measured in meters per second, and the target is change from baseline to 6 months. Continuous outcomes retain the scale of the measurement, so an estimate can describe the size and direction of a change. Here, the registry specifies least-squares means rather than a simple arithmetic mean. In general, a least-squares mean is a model-based estimate that can account for variables included in the statistical model. The registry record does not report which covariates were included or the full model specification.

What does a 95% confidence interval communicate?

In general, a confidence interval shows the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while an interval spanning a broad range leaves more uncertainty about the size of the estimate. The registry lists 95% confidence intervals for the primary outcome, but their limits are not reported in the registry record. Precision therefore cannot be evaluated for the primary estimate or treatment comparisons.

How should group comparisons be understood?

The study had a placebo group and two BIO101 dose groups. The clinical question concerns whether change in gait speed differed between each active-dose group and placebo. In general, a between-group contrast addresses a different question from whether a group changed from its own baseline: change within one group does not by itself establish a difference between groups. The registry record does not report the numerical contrasts, their uncertainty, or p-values, so those comparisons cannot be interpreted statistically from the available record.

What does imputation do?

The registry says missing data were imputed using adjusted Bayesian multiple imputation for non-completers who failed test feasibility and multiple imputation for participants without on-site visit data. In general, multiple imputation creates several plausible completed datasets based on an analysis model, analyzes each dataset, and combines the results to reflect uncertainty associated with missing values. It can preserve more information than analyzing only participants with observed measurements, but it relies on assumptions about the missingness process and the variables included in the imputation model. The registry record does not report the full models, variables, diagnostics, or sensitivity analyses.

Why can over-dispersion matter?

Over-dispersion is a general issue for count outcomes when variability exceeds what a model assumes. It can make standard errors too small if ignored. The primary outcome in SARA-INT is continuous gait speed, not a count, so over-dispersion is not the defining issue for that endpoint. Some secondary outcomes may be expressed in other forms, but their analysis details are not reported in the registry record.

What do planning calculations mean?

In general, sample-size calculations are planning exercises that estimate how many participants per arm may be needed for a specified power under stated assumptions. They do not describe the observed power of a completed trial. The record's planning illustration is based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers an effect set as a stated fraction of the observed effect. These are illustration assumptions, not evidence that they were the original design assumptions. The record does not report a sample-size justification or the trial's original statistical plan. No planning calculation can replace the missing outcome estimates or establish what the trial found.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary gait-speed outcome and numerous secondary measures, including physical function, strength, lean body mass, walking performance, and disability. Testing multiple outcomes or multiple treatment comparisons can increase the chance of at least one apparently unusual result arising by chance. In general, a prespecified multiplicity strategy can control or describe that issue. The registry record does not report whether an adjustment was planned, which comparisons were prioritized, or how the family of tests was defined. Numerical results for the listed secondary outcomes are also not reported in the registry record.

Missing data are a particular concern in this trial. The registry states that >50% of endpoint data were missing due to the COVID pandemic, and notes that this may have affected the ability to deliver expected results. It describes adjusted Bayesian multiple imputation for non-completers who failed test feasibility and multiple imputation for participants without on-site visit data. It also says that data up to 9 months were used when 6-month observations were unavailable for participants enrolled during the pandemic.

In general, imputation depends on assumptions about how missingness relates to observed and unobserved outcomes. The record does not provide the imputation models, diagnostics, sensitivity analyses, or the amount of missingness by group. It also does not report how many participants contributed observed versus imputed endpoint data. The Full Analysis Set is identified, with a partial description of exclusions, but the full population definition is not reported in the registry record. These omissions limit assessment of missing-data bias, population selection, and robustness of the outcome analysis.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (1.4%), partial bowel obstruction (1.4%), orthostatic hypotension (1.4%), coronavirus infection (1.4%), ischemic stroke (1.3%).

The registry reports serious adverse events and other adverse events separately for the three groups. For placebo, the serious-event count affected was 10 among 81 at risk, and the other-event count affected was 48 among 81 at risk; one death was reported. For 175mg BIO101, the corresponding counts were 10 among 75 at risk and 45 among 75 at risk, with no deaths reported. For 350mg BIO101, the counts were 4 among 74 at risk and 38 among 74 at risk, with one death reported.

These figures are descriptive counts, not estimates of whether treatment caused an event. In general, adverse-event comparisons require attention to the definition of an event, duration of observation, completeness of reporting, and uncertainty around group differences. The registry record does not report statistical comparisons for these safety counts, nor does it provide enough detail to determine whether affected counts represent participants with at least one event or event episodes. They should not be converted into a causal conclusion.

The listed serious-event terms include chest pain, partial bowel obstruction, orthostatic hypotension, coronavirus infection, ischemic stroke, and recurrent cardiac decompensation, each with a percentage recorded in the registry. The record does not identify a treatment group alongside each listed term in the available information. The terms and percentages therefore should not be interpreted as a comparative ranking of risk across groups.

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

This record establishes the trial's design and the question it set out to answer: whether either BIO101 dose differed from placebo in change in gait speed on the 400-meter walking test. It also documents the population, dosing schedules, the specified outcome measure, and the use of imputation for some missing observations. Those details help readers understand what the primary analysis was intended to represent.

However, the numerical primary outcome estimates and comparisons are not reported in the registry record. The record therefore does not establish the size or direction of any difference, how precisely it was estimated, or whether a statistical test indicated a difference. A treatment cannot be described as beneficial, ineffective, or equivalent to placebo on the basis of this information alone.

The substantial endpoint missingness reported in the record adds uncertainty about how representative the analyzed data may be of the randomized groups. Imputation can address missing measurements under specified assumptions, but it cannot recover observed outcomes for participants whose data are absent. The use of later observations for some participants also means that follow-up timing may vary for the endpoint analysis. The record does not report sensitivity analyses that would show how conclusions changed under different missing-data assumptions or timing choices.

The safety counts document reported events in each group, but they are not, by themselves, proof of a treatment-caused effect. The available information does not include comparative statistical analyses or enough detail to judge differences in exposure and event ascertainment. The most defensible interpretation is therefore limited: SARA-INT was a randomized, double-blind phase 2 trial with a mobility-focused primary outcome, and the registry record notes substantial pandemic-related missingness. It does not report the numerical primary results needed to characterize the trial's outcome.

13. Why This Trial Matters Statistically

SARA-INT illustrates why a trial's endpoint definition and its result estimates need to be considered together. The primary measure was change in walking speed on a 400-meter test, a continuous outcome intended to capture mobility function. The registry specifies that the result would be expressed as a least-squares mean with a 95% confidence interval. That format would ordinarily allow readers to assess both the estimated change and its precision, but those numerical results are not reported in the registry record.

The record also makes missing data central to the statistical context rather than a minor footnote. It states that >50% of endpoint data were missing because of the COVID pandemic, describes imputation procedures, and notes that some later observations were used when 6-month data were unavailable. These features raise questions about the assumptions underlying the analysis and the comparability of follow-up times. Without detailed sensitivity analyses, readers cannot judge how dependent the result might be on those choices.

More broadly, the study lists several secondary outcome domains alongside its primary measure. When many outcomes and comparisons are assessed, clear reporting of the planned analysis and multiplicity approach is important for distinguishing confirmatory evidence from exploratory findings. Those details are not reported in the registry record. The case demonstrates that a completed status and a detailed outcome definition do not substitute for numerical estimates, analysis details, and transparent reporting of missingness. It also shows why safety counts and efficacy outcomes must be interpreted separately and cautiously.

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 interpreting the primary endpoint is that the registry record does not report its numerical estimates, confidence-interval limits, or treatment comparisons. The direction and size of any difference in gait-speed change therefore cannot be assessed. The record also does not report p-values or sufficient analysis details to evaluate statistical significance.

The trial's endpoint data were affected by the COVID pandemic. The registry reports that >50% of endpoint data were missing, but does not give missingness by group or explain how the missing observations were distributed across participants. Although imputation methods are named, their model specifications and sensitivity analyses are not reported. Use of data up to 9 months for some participants when 6-month data were unavailable may also complicate interpretation of a nominal 6-month outcome; the number of participants affected is not reported in the registry record.

The analysis population is described as the Full Analysis Set, with part of its exclusion criteria stated, but the available description is incomplete. The record does not report the complete population definition, the number included in each primary analysis, or the original statistical plan. It also does not report how multiplicity across the primary and secondary outcomes was handled. These omissions limit assessment of selection, model assumptions, and the robustness of any reported findings. Finally, the adverse-event information is descriptive and does not provide comparative statistical analyses or enough detail to interpret the listed event-term percentages by group.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Double-blind, Placebo-controlled, Randomized INTerventional Clinical Trial (SARA-INT) — NCT03452488.
• Registry record last updated 2024-10-01; status last verified 2024-09.
• Results first posted 2024-10-01.
• 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

SARA-INT was a completed phase 2, randomized, double-blind, parallel-group trial of BIO101 versus placebo in people aged ≥65 years with age-related sarcopenia, including sarcopenic obesity, and at risk of mobility disability. The registry records enrollment of 233 participants and lists two BIO101 doses, 175 mg and 350 mg, alongside placebo. Treatment was intended for 6 months but continued up to 9 months for some participants during the COVID pandemic.

The primary outcome was change from baseline to 6 months in gait speed on the 400-meter walking test, reported as a least-squares mean with a 95% confidence interval. The registry reports >50% missing endpoint data and describes imputation methods and the use of later observations for some participants. Numerical primary outcome estimates and comparisons are not reported in the registry record. Serious and other adverse-event counts are listed by group, but no comparative safety analysis is reported in the available information.