A Study of the Safety and Tolerability of LPCN 1144 in Subjects Who Completed the LPCN 1144-18-002 Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Tolerability of LPCN 1144 in Subjects Who Completed the LPCN 1144-18-002 Trial (NCT04685993), a na phase 2 study. The primary outcome is Safety and Tolerability of LPCN 1144.

2. Clinical Question

Statistically, this is a descriptive safety question rather than a randomized treatment-effect question. Event counts can describe what was recorded among participants in the extension, but without a concurrent comparison they cannot isolate the contribution of LPCN 1144 from other explanations. Prior completion of a different trial defines the extension population; it does not create a control group for this study. The registry record identifies enrollment as 25 and the study status as completed. Details about the characteristics of participants who entered the extension, the amount of follow-up actually observed for each person, and the handling of people who did not complete follow-up are not reported in the registry record.

3. Trial Design

The registry describes NCT04685993 as a Phase 2, open-label extension study of LPCN 1144. It is a single-group study, with no masking and no randomized allocation. The study was intended for adult men with NASH who completed LPCN 1144-18-002. Its stated aim was to evaluate the safety and tolerability of LPCN 1144 in this population.

The sole listed intervention is LPCN 1144, and Treatment A is described as receiving LPCN 1144. No concurrent placebo, standard-care, or other active-treatment group is listed. The record therefore supports a description of events observed in the treatment group, not a randomized comparison of treatment strategies. The design also means that changes over time cannot by themselves distinguish a treatment-related change from changes that might occur without treatment.

Enrollment is listed as 25. The study start date is 2020-11-11, and primary completion is listed as 2022-03-01; the overall status is completed. Those registry fields describe the study record, but do not establish how long each participant was followed or when every outcome was assessed. The primary outcome timeframe is baseline to Week 36.

The record lists one outcome measure and 0 analyses. No detailed statistical analysis plan, sample-size justification, interim analysis plan, dose schedule, eligibility criteria beyond the prior-trial requirement, or participant-flow account is reported in the registry record. The absence of those details prevents a fuller assessment of how the trial was conducted and how the posted safety counts were assembled.

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: Subjects who completed the 38 week study LPCN 1144-18-002 as planned and wanted to continue in this open label extension study

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of LPCN 1144, measured over Baseline to Week 36.

The primary endpoint is titled “Safety and Tolerability of LPCN 1144.” It is defined as the number of participants presenting with treatment-emergent adverse events, with participants as the unit and a timeframe from baseline to Week 36. A count of participants is a binary-style summary at the individual level: a participant either is or is not counted as having the specified event under the endpoint definition. It is not a count of the total number of event episodes.

Safety endpoints are used to describe adverse experiences recorded during treatment and follow-up. They can help characterize what occurred in the study population and provide a structured way to monitor harms. A participant count can be easier to interpret than a raw tally of event episodes when one person might experience repeated events. However, the registry record does not give additional endpoint rules, such as the precise event coding convention, the attribution process, or how recurring events were handled.

The endpoint's timeframe defines the intended observation window, not necessarily the actual follow-up received by every participant. The record does not report participant-level exposure or follow-up duration. Nor does the information available state a total count for participants with any treatment-emergent adverse event under the primary endpoint definition. The serious and other adverse-event figures are separate safety summaries and should not be treated as interchangeable with the primary endpoint unless the registry explicitly establishes that relationship.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical distinctions matter when reading this record. The design determines which comparisons are supported; the endpoint definition determines what is counted; and the completeness of follow-up determines how representative the recorded counts may be. General statistical explanations below clarify these issues without adding results that the registry does not report.

What does a single-group design allow?

A single-group study can describe outcomes among people who received the listed intervention. It has no concurrent group to represent outcomes under an alternative treatment or under no study intervention. As a result, a count in the treated group is not a treatment-versus-control effect. The study's extension setting adds another limit: eligibility required completion of LPCN 1144-18-002, so the enrolled population is defined by participation in that earlier trial. The record does not report how that selection affected the characteristics of people entering the extension.

Randomization, when used, helps balance measured and unmeasured prognostic factors between groups on average. This study is not listed as randomized and has no concurrent control group. Statistical adjustment cannot recreate the information posted by an absent comparator unless suitable data and a justified design are available; neither is described in the registry record. The posted counts should therefore be read descriptively, not as a causal estimate.

What is counted by a participant-level endpoint?

The primary outcome's unit is participants, and its description concerns participants presenting with treatment-emergent adverse events. Participant-level counting records whether each person meets the endpoint definition during the stated window. That differs from counting episodes: a person with repeated events might still contribute once to a participant count, depending on the endpoint rules. The record does not report whether or how repeat events were grouped, how onset and resolution were classified, or how treatment emergence was operationalized.

The serious and other adverse-event summaries also use participants affected. These categories should be kept distinct from a general count of anyone with a treatment-emergent adverse event. They may describe subsets, but the registry record does not provide enough detail to establish exact relationships among the categories. Overlap is not specified, so adding category counts or interpreting them as mutually exclusive would not be justified.

Why do denominators and follow-up matter?

A count is most informative when its denominator and observation window are clear. The safety summaries list 25 participants at risk, while the primary endpoint timeframe is baseline to Week 36. A participant who leaves early may have less opportunity for an event to be observed than someone followed throughout the intended window. The registry record does not report individual follow-up, exposure time, withdrawal details, or missing outcome handling. The at-risk denominator should therefore be understood as the denominator listed for those summaries, not proof that each participant contributed the same amount of observation.

General statistical practice distinguishes a proportion of participants with at least one event from an event rate based on exposure time. An event rate needs an exposure-time denominator and suitable event-count information. Neither is reported in the registry record, so no event rate can be interpreted from these summaries. No new proportion or rate is calculated.

How should uncertainty be understood?

A confidence interval is a range of values compatible with the observed data under a specified statistical model and its assumptions. It communicates uncertainty around an estimate; it does not remove bias in the design or establish causality. The registry record does not report a confidence interval for the posted safety counts, nor does it report a comparative effect estimate. The record also lists 0 analyses, so no model or inferential procedure is documented in the available information.

General methods for sparse binary outcomes can produce imprecise estimates, especially when events are uncommon. Small counts can be compatible with a broad range of underlying risks. A confidence interval, if calculated, would still describe uncertainty under its assumptions and would not supply the missing control group. The posted information does not support a numerical estimate of that uncertainty beyond the event counts and listed value.

What do the planning assumptions mean?

The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. It distinguishes participant-per-arm outputs from total-event outputs for time-to-event settings. These are general planning assumptions, not evidence that the extension itself was designed as a two-arm trial. This study is recorded as single group and does not have a like-for-like control comparison.

No numerical planning illustration, observed effect estimate, or sample-size justification is reported in the registry record. Planning estimates, when available, describe sample sizes for a future design under assumptions; they are not observed power and do not measure the probability that this completed study detected a true effect. The registry record does not report the assumptions or calculations used by the sponsor for the study's enrollment target.

These distinctions keep the interpretation aligned with the record: the posted information describes safety counts in one group, while key inferential details, comparative data, and follow-up information are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment A")
n      <- c(25)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment A  25  10  40.0  21.1  61.3  23.4  59.3  23.4  59.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and 0 analyses. It does not report a multiplicity plan, a hierarchy of outcomes, or a method for controlling the chance of false-positive findings across multiple statistical tests. With no analyses listed, there are no reported hypothesis tests or analysis-specific estimates to evaluate for multiplicity. The absence of a recorded plan does not establish what procedures were used outside the information in the registry record.

Missing-data handling is also not reported in the registry record. There is no account of incomplete Week 36 assessments, withdrawals, reasons for loss to follow-up, or imputation methods. The enrollment field lists 25, and the adverse-event summaries list 25 at risk, but those fields do not establish that all participants had complete endpoint observation or that the analysis population was identical for every outcome.

The record does not describe an intention-to-treat population, a safety population definition, or exclusions from analysis. For a safety endpoint, the population may be defined using exposure or available follow-up, but the registry does not state the rule used for this trial. This limits assessment of whether the reported counts include all enrolled participants and how participants with partial follow-up were treated.

Missingness can affect interpretation when the chance that an outcome is unobserved is related to the outcome or to a participant's health. General statistical methods may examine patterns of missingness and test sensitivity to assumptions, but no such analyses are reported in the registry record. Without information on completeness, the posted figures remain descriptive summaries rather than a complete account of the endpoint for every enrolled participant.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (4.0%).

The serious adverse-event summary lists 25 participants at risk and 1 participant affected. The other adverse-event summary lists 25 at risk and 2 participants affected. The registry also lists 1 death. These are separate reported figures; the record does not explain whether the death overlaps with the serious adverse-event count or whether the other-event category overlaps with either of them. They should not be added together or treated as mutually exclusive groups.

Respiratory Failure is listed as the top serious adverse-event term, with a reported value of 4.0%. The registry record does not explain the term's coding rules, the time window for that term, or how the displayed value relates to the participant-level count. It is appropriate to quote the value as reported, but not to infer additional counts or a treatment relationship from it.

Serious adverse events and other adverse events are safety classifications, not automatic judgments about causation. The registry record does not state whether any event or death was considered related to LPCN 1144. In a single-group study, these figures describe recorded events among participants receiving the intervention; without a concurrent comparator, they do not estimate an excess risk attributable to treatment. The record also does not report event severity grading beyond the serious-versus-other summaries, event timing, or participant-level follow-up.

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

The record establishes that NCT04685993 was a completed, Phase 2, open-label extension study of LPCN 1144 in adult men with NASH who completed LPCN 1144-18-002. It identifies safety and tolerability as the study aim and gives a primary outcome focused on participants with treatment-emergent adverse events from baseline to Week 36. It also posts single-group safety summaries: 1 participant affected by a serious adverse event, 2 affected by other adverse events, and 1 death, with 25 listed at risk in the adverse-event summaries.

These registry entries describe what the registry record reports; they do not establish the cause of events, the comparative safety of LPCN 1144, or the likelihood of an event in a different population. The single-group design has no concurrent control, and the record does not report a comparative effect estimate or inferential analysis. The serious-event count and other-event count do not substitute for the overall primary endpoint result, which is not reported in the registry record.

The record also does not establish whether every participant completed the intended follow-up, how missing outcome information was handled, or whether the death was considered treatment-emergent or treatment-related. Without those details, the counts cannot be interpreted as complete participant-level risk estimates for the full intended observation period. The value of 4.0% for Respiratory Failure is reported as the top serious adverse-event term; it should not be used to infer unreported event counts or causal attribution.

Thus, the result supports a limited descriptive reading of the safety summaries in the enrolled extension group. It does not prove that treatment caused a reported event, establish that treatment prevented events, or determine how outcomes would differ under another approach. Broader claims would require information and comparisons not reported in the registry record.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between safety surveillance and comparative treatment-effect estimation. A single-group extension can document events observed during treatment and follow-up in a population defined by prior trial completion. That descriptive information can be useful, but it cannot answer what would have occurred in a comparable group without LPCN 1144 or under another intervention.

The endpoint's participant-based count also highlights why outcome definitions matter. A count of people affected is not the same as a count of event episodes, and serious-event summaries are not automatically equivalent to a broad treatment-emergent adverse-event endpoint. When the registry does not explain category overlap or event coding, interpretation needs to remain close to the stated definitions rather than treating distinct safety summaries as interchangeable.

Denominators and observation time matter alongside counts. The adverse-event summaries list 25 at risk, while the primary timeframe extends from baseline to Week 36. The record does not report whether follow-up was complete for each participant or how incomplete observation was handled. Such details affect how confidently a reader can generalize the observed summaries to the intended follow-up period.

Finally, the record lists 0 analyses and reports no comparative estimate or confidence interval. This limits assessment of statistical uncertainty and makes it especially important not to treat a small count as proof of low risk or as evidence of causality. The trial is a useful example of how a completed study can have a stated endpoint and posted safety counts while leaving key inferential, follow-up, and analysis details unreported in the registry record.

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.

The single-group, open-label design is the main limitation for causal interpretation. There is no concurrent comparator, and treatment masking is listed as none. Event counts therefore cannot establish whether LPCN 1144 caused, prevented, or changed the occurrence of an adverse event relative to an alternative. The prior-trial completion requirement further defines a selected extension population; the record does not report how this population compares with people who did not enter the extension.

Several details needed to assess the safety summaries are not reported in the registry record. These include participant characteristics, eligibility criteria beyond prior-trial completion, dosing and exposure, adherence, participant flow, event definitions, attribution procedures, and individual follow-up. The record also does not report missing-data methods, the analysis-population definitions, or whether all participants contributed data through Week 36.

The overall number of participants meeting the primary treatment-emergent adverse-event definition is not reported in the registry record. The serious and other adverse-event figures should not be assumed to be that primary outcome, and their overlap is not specified. The relationship between the listed death and the serious adverse-event summary is also not described. The Respiratory Failure term is reported at 4.0%, but coding and denominator details are not stated.

Finally, the registry lists 0 analyses and no comparative estimate or confidence interval. It does not report a detailed statistical analysis plan, multiplicity procedures, interim analyses, or the sponsor's sample-size justification. The record's general planning assumptions are not evidence of the design used in this single-group extension and do not provide a numerical planning result. These gaps constrain interpretation to the registry entries actually posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Safety and Tolerability of LPCN 1144 in Subjects Who Completed the LPCN 1144-18-002 Trial — NCT04685993.
• Registry record last updated 2024-07-17; status last verified 2024-03.
• Results first posted 2024-07-17.
• 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

NCT04685993 is listed as a completed Phase 2, open-label extension study of LPCN 1144 in adult men with NASH who completed LPCN 1144-18-002. The design is single group, with no masking and no comparator. Enrollment is listed as 25; the study start date is 2020-11-11, and primary completion is listed as 2022-03-01.

The primary outcome is the number of participants presenting with treatment-emergent adverse events from baseline to Week 36. The registry lists 1 outcome measure and 0 analyses. Safety summaries list 25 at risk, 1 participant affected by a serious adverse event, 2 affected by other adverse events, and 1 death. Respiratory Failure is the top serious adverse-event term at 4.0%.

The registry record does not report a comparator, a primary endpoint total, an inferential analysis, or key details about follow-up and missing data. The event figures are descriptive and do not establish treatment causation or comparative risk.