The Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis (NCT04134091), a randomized phase 2 study. The primary outcome is Absolute Change in Hepatic Fat Fraction Based on MRI-PDFF Measurements in LPCN 1144 Treated Subjects Compared to Placebo..

2. Clinical Question

The clinical question is about an imaging measure of liver fat over the stated period, not a direct measure of symptoms, long-term health, or clinical events. The registry also lists secondary outcomes at Week 36, including histopathological assessments of NASH resolution and liver-fibrosis changes. Those outcomes address related but distinct questions and should not be treated as substitutes for the primary MRI-PDFF endpoint.

3. Trial Design

The registry describes NCT04134091 as a Phase 2, randomized, parallel-group study of oral LPCN 1144 in adult men with biopsy-confirmed NASH. It lists three groups: LPCN 1144 Formulation A, LPCN 1144 Formulation B, and placebo. The study was sponsored by Lipocine Inc. and is recorded as completed. The registry lists enrollment as 56.

The arm-level primary results include 18.0 participants in Treatment A, 19.0 in Treatment B, and 19.0 in Treatment C. These are the denominators attached to the posted primary endpoint estimates; they should not be assumed to describe every analysis population or every later outcome. The registry record does not report why denominators vary across outcomes or whether particular participants were excluded from particular analyses.

The primary endpoint is the absolute change in hepatic fat fraction based on MRI-PDFF measurements, from baseline to Week 12. The reported arm estimates are least-squares means with 95% confidence intervals. The registry reports ANCOVA superiority analyses for each LPCN 1144 group compared with placebo. Secondary outcomes include imaging and histopathology measures, several assessed at baseline and Week 36. The record also contains safety counts.

The study is described as double-blind in its official title and brief summary; its masking designation is quadruple. The record does not explain which people or roles were masked, so the precise masking arrangements are not reported in the registry record. Details of dose, treatment adherence, allocation procedures, and the statistical-analysis plan are also 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

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.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change in Hepatic Fat Fraction Based on MRI-PDFF Measurements in LPCN 1144 Treated Subjects Compared to Placebo., measured over Baseline and Week 12.

The primary endpoint measures change in hepatic fat fraction using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). It is specified as an absolute change from baseline to Week 12 and is expressed as a percentage of liver fat. A negative change indicates a lower measured liver-fat fraction at Week 12 than at baseline; this describes the direction of the measurement, not its clinical importance.

MRI-PDFF provides a quantitative imaging measure of liver fat. In general, continuous imaging measures can capture changes across a range rather than reducing each participant’s result to a yes-or-no category. The registry reports the primary outcome as a least-squares mean for each group, with a 95% confidence interval. Such a mean describes the estimated group-level change under the reported analysis, while the interval conveys uncertainty around that estimate.

The primary endpoint is distinct from the Week 36 secondary histopathology outcomes. The latter concern readings of liver biopsies and include NASH resolution and fibrosis-related assessments. A change in MRI-PDFF does not, by itself, establish a corresponding change in histopathology, symptoms, or other outcomes. The registry record does not report a threshold for a clinically meaningful MRI-PDFF change, nor does it explain how the primary endpoint was selected over the listed secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: each participant’s MRI-PDFF measurement can vary over a range, and the reported group result is a mean change rather than a count of participants crossing a threshold. The registry labels the arm estimates as least-squares means. In general, a least-squares mean is a model-based estimate of a group mean; the particular model and any covariates determine how it is adjusted. The record identifies ANCOVA for the pairwise primary comparisons but does not report the covariates, model specification, or missing-data approach. It is therefore not possible to determine from the registry record exactly how the arm estimates were adjusted.

What does a confidence interval describe?

A confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider one, while an interval’s location gives the range of values compatible with the estimate and method. The reported primary intervals are for the separate arm estimates. They are not intervals for the difference between an LPCN 1144 group and placebo. Comparing overlap or non-overlap of separate intervals is not a replacement for the reported pairwise test, because the uncertainty in a contrast depends on the joint analysis and its covariance structure.

The primary arm intervals are reported at the 95% level. Treatment A’s interval and Treatment B’s interval are below zero; Treatment C’s interval includes zero. In general, an interval that includes zero means that zero is among the values compatible with that arm’s estimated change at the stated confidence level. This is a within-arm statement, not the result of a test comparing that arm with another. The registry’s reported ANCOVA tests address the active-versus-placebo comparisons.

Why use ANCOVA?

In general, analysis of covariance (ANCOVA) models an outcome using group assignment and one or more additional variables. It can estimate adjusted group comparisons and may account for baseline values or other prespecified covariates. The registry reports ANCOVA for the primary superiority tests, but it does not report which variables entered the model or whether the Week 12 outcome was modeled directly or through a change score. Those details are not reported in the registry record. Accordingly, the sponsor’s reported tests can be described, but their model cannot be fully reconstructed from the posted summaries.

How should the binary secondary outcomes be read?

For the posted histopathology outcomes, the registry reports participant counts and Fisher exact tests. In general, Fisher’s exact test evaluates an association in a two-group binary-outcome comparison and is useful when counts are small. A count is easier to interpret alongside its denominator: the same count can represent different observed proportions in groups of different sizes. The outcome-specific denominators in the registry are not uniform, and the record does not explain why they vary. The reported Fisher exact p-values are sponsor results; recalculated risk differences and their confidence intervals are unadjusted comparisons based on the posted counts.

A risk difference describes the difference between two observed proportions, with its sign depending on the order of the groups. Its confidence interval reflects uncertainty in that difference. If the interval includes zero, the data are compatible with no difference under that interval method as well as with differences in either direction. An unadjusted p-value does not account for testing several outcomes or comparisons. It should not be read as a confirmatory result unless the analysis plan and multiplicity procedure support that interpretation; those details are not reported in the registry record.

What do the planning illustrations mean?

In general, sample-size planning uses assumptions about the effect to be detected, the significance level, allocation, and the statistical method. The planning illustrations associated with the secondary comparisons use the observed effect or stated fractions of it, a two-sided significance level of 0.05, equal allocation between two groups, and a normal approximation. They are illustrations based on observed results, not the trial’s own design calculation and not observed power. Observed effects from small groups can be imprecise, so planning figures based on them should not be treated as reliable forecasts without further assumptions.

The registry record does not report the trial’s original sample-size justification, target power, or planned enrollment calculation. It also does not report whether interim analyses were conducted. The posted planning assumptions should therefore be kept separate from the trial’s design and from the reported results.

10. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses compare each LPCN 1144 formulation with placebo using ANCOVA. The registry reports superiority for Treatment A versus Treatment C at p < 0.001 and for Treatment B versus Treatment C at p < 0.001. These reported tests are the primary inferential results available in the registry record.

The arm-level least-squares means and their confidence intervals do not contain the pairwise contrast estimates, their confidence intervals, or the information needed to reconstruct those quantities reliably. The registry’s posted details do not permit an independent recalculation of the primary pairwise comparisons from the arm summaries. This is different from a comparison where recalculated and sponsor-reported results conflict: the registry record does not indicate such a discrepancy for the primary endpoint. The sponsor’s reported ANCOVA results should therefore be presented as reported, without suggesting that an unavailable reconstruction confirms or overturns them.

For the binary secondary outcomes, unadjusted recalculations from posted counts are descriptive checks, not replacements for the sponsor’s Fisher exact analyses. They may differ because of methods and rounding, and multiple testing remains relevant. The registry record does not provide enough detail to assess the full analysis plan or reconcile every methodological choice.

11. Multiplicity, Missing Data and Analysis Populations

The registry record reports a primary endpoint and numerous secondary outcomes, as well as multiple pairwise comparisons. It does not report a multiplicity-control procedure, a testing hierarchy, or whether any secondary outcomes were designated as confirmatory. In general, testing multiple hypotheses without adjustment increases the chance of obtaining one or more small p-values by chance. A nominal p-value can therefore be informative about an individual comparison while still providing limited evidence when viewed among many tests. The posted secondary p-values should not be treated as if they were adjusted for the full set of outcomes unless such an adjustment is reported.

Missing-data methods are not reported in the registry record. The posted denominators differ across outcomes, but the record does not explain whether this reflects missing measurements, eligibility for a particular assessment, exclusions, or another reason. It also does not report imputation methods, sensitivity analyses, or how participants without a Week 12 or Week 36 measurement were handled. Without those details, it is not possible to assess whether missing outcomes could have affected the estimates.

The analysis populations are not reported in the registry record. In particular, the posted information does not specify whether analyses followed intention-to-treat, modified intention-to-treat, per-protocol, or another population definition. It also does not describe exclusions after randomization or the treatment of participants who discontinued. The arm denominators attached to individual outcomes should consequently be read as the denominators for those posted results, not as a complete account of trial participation.

The record does not report the original sample-size justification, planned power, interim-analysis procedures, or a full statistical-analysis plan. These omissions limit assessment of whether the analyses and populations followed prespecified methods. They also prevent a full evaluation of the potential effects of multiplicity and missing data.

12. 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: acute myocardial infarction (5.6%), cardio-respiratory arrest (5.6%), coronary artery disease (5.6%), hyperprolactinemia (5.6%), lung cancer metastatic (5.6%).

The registry reports serious adverse events for Treatment A, Treatment B, and placebo in counts of 2, 2, and 1 participants, respectively. The corresponding groups at risk are reported as 18, 19, and 19. It reports other adverse events in counts of 12, 11, and 16 participants, with the same group-specific denominators. Deaths are reported as 1, 0, and 1, respectively. These are descriptive safety counts; the registry record does not provide a causal assessment for individual events.

The registry also lists serious-event terms with percentages, including acute myocardial infarction, cardio-respiratory arrest, coronary artery disease, hyperprolactinemia, lung cancer metastatic, and corona virus infection. The posted information does not establish whether any event was caused by study treatment, nor does it provide the clinical context needed to interpret individual events. Serious adverse events and other adverse events are different reporting categories and should not be combined into a single measure.

These counts should be read with the group denominators and the limitations of the available safety detail. The registry record does not report event onset, duration, severity grading beyond the serious-event classification, exposure time, or a fuller account of how adverse events were collected. The counts alone are not a comparative safety analysis and cannot determine whether observed differences reflect treatment, chance, or other factors.

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

The primary results describe estimated changes in MRI-PDFF liver-fat fraction from baseline to Week 12 in three randomized groups. The estimates are negative in all groups, and the registry reports ANCOVA superiority tests for each LPCN 1144 formulation compared with placebo, both at p < 0.001. These findings concern the specified imaging endpoint and the reported analysis. They do not by themselves establish the clinical importance of the change.

The primary endpoint is not a direct measure of how participants felt or functioned, nor does it report long-term clinical outcomes. The registry record does not report a threshold for a clinically meaningful change, long-term follow-up results, or evidence that an imaging change predicts later outcomes in this study. The posted primary outcome therefore cannot establish effects on symptoms, disease progression, or other health outcomes not measured by that endpoint.

The secondary biopsy outcomes provide additional information about histopathology at Week 36, but they are not interchangeable with the Week 12 imaging result. Their denominators and precision vary, and the registry record does not report multiplicity control or a hierarchy that would establish them as confirmatory. They should be considered alongside, rather than merged with, the primary finding.

The registry record also does not supply full analysis-population definitions, missing-data methods, treatment exposure details, or a complete statistical-analysis plan. These gaps limit how fully the results can be assessed. The posted findings are evidence about measurements and comparisons recorded for this trial; they are not a standalone basis for a treatment decision or a conclusion about all people with NASH.

14. Why This Trial Matters Statistically

This trial is statistically notable for reporting a continuous imaging endpoint alongside later binary histopathology outcomes. The distinction matters: continuous measurements retain information about degree of change, while binary outcomes classify participants according to whether a stated outcome occurred. Each design raises different questions about effect estimation, precision, and interpretation.

The primary endpoint estimates are accompanied by 95% confidence intervals, and the registry reports ANCOVA comparisons against placebo. This makes it important to distinguish arm-level change from the between-group contrast that addresses the comparative question. The posted arm estimates show the direction and uncertainty of within-group change; the sponsor-reported ANCOVA tests address the pairwise comparisons. Without pairwise estimates and intervals, the magnitude and precision of those contrasts cannot be assessed directly from the posted primary summaries.

The secondary outcomes illustrate another central issue in clinical-trial interpretation: several outcomes and comparisons can generate a collection of p-values that is not equivalent to one prespecified test. The record does not report multiplicity control or a hierarchy, so secondary statistical signals deserve cautious interpretation. The outcome-specific denominators also reinforce why counts should be read with their denominators and uncertainty, rather than as isolated totals.

Finally, planning illustrations based on observed effects are not observed power and are not the trial’s own sample-size justification. This distinction is important because observed effects from small groups can be unstable. Together, the endpoint structure, analysis reporting, and missing design details make this record a useful example of separating descriptive estimates, sponsor-reported tests, exploratory findings, and information the registry does not report.

15. 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.

Several limitations specific to this record affect interpretation. The primary results give arm-level least-squares means and confidence intervals, but do not report the pairwise treatment-versus-placebo effect estimates or their confidence intervals. The sponsor-reported ANCOVA p-values indicate the reported test results, but the registry does not provide the model covariates or enough detail to reproduce the analysis.

The registry describes an adult-male population with biopsy-confirmed NASH, but does not provide participant characteristics or further eligibility criteria in the posted details. This limits assessment of how the enrolled group relates to other populations. The record also does not report formulation doses, adherence, treatment exposure, or detailed discontinuation information.

Outcome denominators vary across the secondary results, and the reasons are not reported in the registry record. Missing-data methods and analysis-population definitions are also absent, limiting assessment of potential bias from incomplete measurements or post-randomization exclusions. The Week 36 binary outcomes have small denominators, so their estimates may be imprecise and sensitive to individual outcomes.

The registry record does not report a multiplicity procedure, a secondary-outcome hierarchy, or the original sample-size justification. Consequently, the secondary p-values cannot be interpreted as adjusted confirmatory evidence, and planning illustrations based on observed effects should not be confused with the trial’s design assumptions. The posted safety counts lack event-level clinical context and do not establish causality. These limitations do not erase the reported results, but they constrain the strength and scope of conclusions that can be drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Efficacy, Safety and Tolerability of Oral LPCN 1144 in Subjects With Nonalcoholic Steatohepatitis — NCT04134091.
• Registry record last updated 2023-12-14; status last verified 2023-12.
• Results first posted 2023-12-14.
• 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.

19. Record Summary

NCT04134091 is a completed Phase 2 randomized, parallel-group, placebo-controlled study sponsored by Lipocine Inc. It enrolled adult men with biopsy-confirmed NASH and compared LPCN 1144 Formulation A, LPCN 1144 Formulation B, and placebo. The registry lists enrollment as 56.

The primary endpoint was absolute change in MRI-PDFF hepatic fat fraction from baseline to Week 12. The registry reports negative least-squares mean changes in all groups and ANCOVA superiority tests for each formulation versus placebo, both at p < 0.001. Secondary outcomes include Week 36 histopathology assessments. The record does not report full model details, analysis populations, missing-data methods, or multiplicity procedures, which limits interpretation of the posted results.