Saroglitazar Magnesium 4 mg for Nonalcoholic Fatty Liver Disease (NAFLD) in People Living With HIV in the US: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Saroglitazar Magnesium 4 mg for Nonalcoholic Fatty Liver Disease (NAFLD) in People Living With HIV in the US (NCT05211284), a randomized phase 2 study. The primary outcome is To Evaluate the Effect of Saroglitazar Magnesium 4 mg Compared With Placebo on Changes in Hepatic Fat Content Measured by MRI Proton Density Fat Fraction (MRI PDFF).

2. Clinical Question

This is the question the revised endpoint was intended to address, not a question answered by posted efficacy results. The record states that all 4 participants were prematurely terminated before completing their planned treatment and before any efficacy data. It therefore does not provide a treatment-effect estimate for the primary question.

The listed secondary aims include MRI-PDFF, FibroScan/VCTE measures, and non-invasive markers of fibrosis and steatosis. These describe planned areas of assessment; they should not be read as evidence that the assessments were completed or that results were available.

3. Trial Design

The trial was registered as a phase 2, randomized, double-blind, placebo-controlled, multicenter parallel-group study. Its title identifies the intended population as people living with HIV in the US with NAFLD. Quadruple masking is recorded, but the registry record does not identify which roles or groups were masked. Details of the randomization procedure, allocation ratio, or sites are not reported in the registry record.

The intervention was Saroglitazar Magnesium 4 mg, taken orally once daily in the morning before breakfast without food. The placebo arm was described as receiving a placebo tablet on the same schedule. Both arms had a planned treatment duration of 24 weeks. These are descriptions of the planned regimen; the record states that the enrolled participants did not complete their planned treatment.

The study began on 2022-12-08, had a listed primary completion date of 2023-10-02, and is recorded as terminated. The enrollment was 4. The record explains that these participants enrolled under protocol V3.0, which had a biopsy-driven primary endpoint. Due to recruitment challenges, the outcome measure was modified to MRI-PDFF in protocol V4.0.

All 4 participants were prematurely terminated before completing their planned treatment and before any efficacy data. Consequently, the design description explains the planned comparison, while the available record does not support an estimate of the intended treatment contrast. The sponsor is Zydus Therapeutics Inc.

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: The 4 participants were enrolled under protocol V3.0, with biopsy-driven primary endpoint. Due to recruitment challenges, the outcome measure was modified to MRI-PDFF in the protocol V4.0. All 4 participants were prematurely terminated before completing their planned treatment before any efficacy data could be collected. No participants were enrolled under the revised protocol V4.0 as the study was terminated. Consequently, no MRI-PDFF based efficacy data were collected or analyzed

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: Safety Population

6. Primary Endpoint

The registry lists the primary outcome as To Evaluate the Effect of Saroglitazar Magnesium 4 mg Compared With Placebo on Changes in Hepatic Fat Content Measured by MRI Proton Density Fat Fraction (MRI PDFF), measured over Week 24/EOT.

The primary endpoint was intended to measure change from baseline in hepatic fat content using MRI proton density fat fraction (MRI-PDFF), with assessment at Week 24/end of treatment. MRI-PDFF is an imaging-based measure of the proportion of liver tissue signal attributable to fat. In general, measuring change from baseline asks how a participant’s measurement at follow-up differs from their starting measurement, rather than describing follow-up values alone.

The registry record says the original protocol, V3.0, used a biopsy-driven primary endpoint, and that the outcome measure was changed to MRI-PDFF in protocol V4.0 because of recruitment challenges. The record does not report further details about the endpoint definition, such as a specific MRI-PDFF summary measure or how measurements were to be combined across participants.

In general, MRI-based fat measurement can provide a non-invasive way to quantify hepatic fat. The endpoint’s intended role was to compare change in hepatic fat content between the saroglitazar and placebo groups. However, the record states that all 4 participants stopped prematurely before completing planned treatment and before any efficacy data. No primary endpoint result or between-group estimate is reported in the registry record, so the intended measure cannot be used to judge the comparative effect in this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization mean in this study?

Randomization is a method for assigning participants to treatment groups by chance. In general, it is intended to reduce systematic differences between groups at the start of a study, so that a comparison can be interpreted as a comparison of assigned treatments rather than a comparison of deliberately selected groups. The registry identifies this trial as randomized, but does not report the randomization sequence, allocation ratio, or procedures used to conceal assignments. With 4 participants and no efficacy data, the record cannot show whether randomization produced balanced groups or support an efficacy comparison.

What does masking add?

The trial is described as double-blind and as having quadruple masking. In general, masking means keeping treatment assignments unknown to specified people involved in a trial, which can reduce the chance that knowledge of assignment influences care, measurement, or reporting. The registry does not identify which people were masked or provide details of how masking was maintained. The design labels alone do not establish that outcomes were measured or analyzed.

How should the endpoint comparison be understood?

The planned primary endpoint was change from baseline in hepatic fat content measured by MRI-PDFF at Week 24/end of treatment. In general, an analysis of change compares the follow-up measurement with the baseline measurement for each participant, then compares the changes between groups. An estimate would describe the size and direction of that contrast. The registry record does not report a primary result, an analysis method, or data from which the contrast can be interpreted. It specifically states that all 4 participants were terminated before completing planned treatment and before any efficacy data.

What do uncertainty measures usually convey?

In general, a confidence interval expresses statistical uncertainty around an estimate: narrower intervals indicate greater precision under the method’s assumptions, while wider intervals indicate less precision. A p-value, when reported, measures how unusual the observed data would be under a specified null hypothesis and model; it is not the probability that a treatment is effective. Neither measure is available for the primary comparison in the registry record. It would be inappropriate to infer statistical significance or precision from the enrollment count alone.

Why can small studies be difficult to interpret?

In general, small studies tend to provide less information for estimating treatment effects, and estimates can be sensitive to the outcomes of individual participants. They may also provide limited information about uncommon events. These are general statistical considerations, not estimates of the effect or uncertainty in this trial. The enrollment of 4 and the absence of efficacy data mean that no primary treatment-effect estimate is reported to assess.

What does an over-dispersion adjustment mean?

In general, over-dispersion refers to data varying more than a statistical model expects. For count outcomes, for example, a model that assumes a particular level of variability may understate uncertainty if the observed variation is larger. An adjustment can widen uncertainty estimates to reflect that additional variation. The registry record does not report an analysis model or an over-dispersion adjustment for this trial, and no outcome estimates are available to which such an explanation could be applied.

What are the planning sample-size illustrations?

In general, sample-size calculations estimate how many participants might be needed under stated assumptions about an effect, significance level, allocation, and statistical model. They are planning illustrations, not observed power and not evidence that a treatment effect exists. The record’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a fraction of an observed effect. Since the registry record reports no efficacy data and no primary treatment-effect estimate, an observed effect cannot be evaluated from this record. Any planning illustration should be read as conditional on its assumptions, not as a result of the trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures and 0 analyses. The primary outcome was intended to assess change in hepatic fat content by MRI-PDFF at Week 24/end of treatment. The listed secondary aims include liver fat, FibroScan/VCTE measures, and non-invasive markers of fibrosis and steatosis. Multiple outcomes create a general statistical issue: if many hypotheses are tested, the chance of at least one apparently positive finding can increase unless the testing strategy accounts for multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a testing strategy.

The record does not report an analysis population, such as whether the planned analysis would include all randomized participants or only participants who completed treatment. It also does not describe how missing measurements, early termination, or incomplete treatment would be handled. These details are important in general because the analysis population and missing-data approach can affect both the estimate and its interpretation.

All 4 participants were prematurely terminated before completing planned treatment and before any efficacy data. No efficacy analysis is reported in the registry record, so it is not possible to assess how missing outcome measurements were handled or whether outcomes were collected under the revised endpoint. The record also does not report interim analyses or stopping rules. The reason given for the endpoint modification is recruitment challenges; further procedural details are not reported in the registry record.

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 non-serious adverse event terms

The registry reports serious adverse events for 0 of 3 participants at risk in the Saroglitazar Magnesium 4 mg group and 0 of 1 participant at risk in the placebo group. It reports 0 deaths in both groups. For other adverse events, the record reports 0 of 3 participants in the saroglitazar group and 1 of 1 participant in the placebo group as affected.

These are counts from a trial with 4 enrolled participants, not stable estimates of event rates or evidence of a comparative safety difference. In general, event counts describe what was reported among participants at risk; they do not by themselves establish whether an event was caused by treatment. The registry record does not provide event descriptions, timing, severity, duration, or an assessment of relatedness for the other adverse event. It also does not provide enough detail to interpret exposure time across groups. The absence of reported serious events in these small groups should not be taken as evidence that serious events cannot occur.

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

The record establishes that a randomized, masked, placebo-controlled phase 2 trial was planned to study saroglitazar magnesium in people living with HIV and NAFLD. It records an enrollment of 4, a planned 24-week treatment period, and a primary question about change in hepatic fat content measured by MRI-PDFF. It also documents that the endpoint changed from a biopsy-driven measure under protocol V3.0 to MRI-PDFF under protocol V4.0 because of recruitment challenges.

The record does not establish what effect saroglitazar magnesium had on hepatic fat content. It states that all 4 participants were prematurely terminated before completing planned treatment and before any efficacy data. There is no reported primary endpoint estimate, treatment-group contrast, confidence interval, or test result. The secondary outcomes are listed as intended assessments, not as observed findings.

In general, an inconclusive or unavailable result is different from evidence that two treatments have the same effect. No efficacy estimate is reported, so the record cannot establish equivalence, non-inferiority, benefit, or absence of benefit. It also cannot quantify the size or precision of a treatment effect.

The safety counts describe a small set of participants and do not establish a complete safety profile. The record reports no serious adverse events and no deaths in either group, and one other adverse event in the placebo group. These observations do not establish that treatment caused or prevented events.

The central interpretation is therefore about what was and was not observed in the registry record: the study’s planned comparison is identifiable, but its efficacy question remains unanswered by posted results.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a planned clinical question and an answer supported by outcome data. A randomized design can be intended to support a fair comparison, but randomization alone cannot produce an effect estimate when efficacy data are unavailable. Here, the record reports 4 enrolled participants, premature termination before planned treatment was completed, and no efficacy data.

The change in primary endpoint is also relevant to interpreting the study’s history. The original protocol was biopsy-driven, while the endpoint was changed to MRI-PDFF in protocol V4.0 because of recruitment challenges. Endpoint changes can alter what a study is designed to measure. In general, readers need to know when and why an endpoint changed, and whether the revised measure was collected and analyzed. The record gives the reason for the change but does not report whether MRI-PDFF efficacy measurements were obtained.

The record also demonstrates why outcome lists and sample-size illustrations should not be mistaken for findings. Secondary outcomes describe planned assessments, while planning calculations depend on assumptions and do not substitute for observed comparisons. With no primary efficacy analysis reported, there is no treatment-effect estimate whose precision or clinical relevance can be assessed.

Finally, sparse safety counts require cautious interpretation. The reported counts are descriptive observations among a small number of participants, not a definitive comparison of adverse-event risk. Together, these features make the trial a useful example of how design information, endpoint history, data availability, and uncertainty all matter when interpreting a clinical study.

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 most consequential limitation is that the trial ended before any efficacy data were available. The record reports 4 participants enrolled and states that all were prematurely terminated before completing planned treatment. No primary endpoint result or secondary efficacy result is reported in the registry record. As a result, neither the intended MRI-PDFF comparison nor the listed secondary aims can be evaluated from posted efficacy findings.

The primary endpoint changed during the trial. Participants enrolled under protocol V3.0, which had a biopsy-driven primary endpoint, and the outcome measure was modified to MRI-PDFF in protocol V4.0 due to recruitment challenges. The record does not report further details about the timing of the change, whether the revised endpoint was collected, or how any data from different protocol versions would have been handled.

The enrollment was 4, leaving very limited information even for descriptive comparisons. The record does not report the allocation ratio, group-specific efficacy measurements, analysis populations, statistical analysis methods, missing-data procedures, or multiplicity strategy. It also does not report details about which roles were masked. These omissions prevent assessment of how the intended analysis would have been conducted.

The safety record is also limited: group counts are small, and details about event type, severity, timing, and relatedness are not reported. The registry record describes the study as terminated and gives recruitment challenges as the reason for modifying the endpoint, but further reasons for termination are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Saroglitazar Magnesium 4 mg for Nonalcoholic Fatty Liver Disease (NAFLD) in People Living With HIV in the US — NCT05211284.
• Registry record last updated 2025-09-02; status last verified 2025-08.
• Results first posted 2025-07-16.
• 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

NCT05211284 is a phase 2 randomized, double-blind, placebo-controlled, multicenter parallel-group trial of Saroglitazar Magnesium 4 mg for NAFLD in people living with HIV in the US. The planned regimen was a daily oral tablet before breakfast without food for 24 weeks, compared with placebo.

The trial began on 2022-12-08, has a listed primary completion date of 2023-10-02, and is recorded as terminated. Enrollment was 4. The primary endpoint was change from baseline in hepatic fat content measured by MRI-PDFF at Week 24/end of treatment. The endpoint was modified from a biopsy-driven measure in protocol V3.0 to MRI-PDFF in protocol V4.0 due to recruitment challenges.

All 4 participants were prematurely terminated before completing planned treatment and before any efficacy data. The registry record lists 17 outcome measures and 0 analyses. It reports no serious adverse events or deaths in either group, and one other adverse event in the placebo group.