Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis (NCT04604652), a na phase 2 study. The primary outcome is Percent Change in Alkaline Phosphatase (ALP) at Week 12 Compared to Baseline.

2. Clinical Question

3. Trial Design

This is a Phase 2, open-label, single-group study of HTD1801 (BUDCA) in adults with primary biliary cholangitis and an inadequate response to standard therapy. The registry lists allocation as NA, masking as none, and a single-group model. Accordingly, the design does not provide a concurrent randomized control group for comparison. The study is marked completed, with enrollment of 24. The registry lists a start date of 2021-05-27 and a primary completion date of 2022-05-31.

The intervention is HTD1801 250 mg tablets, dosed at 1000 mg BID with food. The stated study purpose is to evaluate safety and tolerability over 12 weeks. The primary endpoint is percent change in ALP from baseline to Week 12. The registry also lists changes in total bilirubin, gamma-glutamyl transferase, total cholesterol, immunoglobulin M, GLOBE score, and pruritus measured by VAS as secondary outcomes.

The registry defines the primary analysis population as the ITT Population, including all subjects who received at least one dose of HTD1801. It does not report further details about the analysis plan, such as how missing observations were handled or whether analyses were adjusted for other factors. The endpoint’s numerical results are also not reported in the registry record. Thus, the design and intended measurements can be described, but the posted information does not permit an assessment of the observed ALP change or its uncertainty.

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: A total of 46 subjects were screened of which 24 subjects were eligible and enrolled in the study. Subjects discontinued use of ursodeoxycholic acid (UDCA) at baseline prior to transitioning to HTD1801.

Overall Study

Analysis population for the primary outcome, as defined in the registry: ITT Population: Included all subjects that received at least one dose of HTD1801

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 Percent Change in Alkaline Phosphatase (ALP) at Week 12 Compared to Baseline, measured over Baseline to Week 12.

The primary endpoint is percent change in serum alkaline phosphatase (ALP) from baseline to Week 12. ALP is a biochemical measure, and the registry identifies it as the measure used to evaluate HTD1801’s effects in adults with PBC who had an inadequate response to standard therapy. The eligibility description refers to persistently elevated ALP at least 1.5 times the upper limit of normal despite adequate UDCA treatment for at least 6 months. The registry states that a reduction in ALP represents an improvement.

Percent change expresses the endpoint relative to baseline rather than as a raw concentration change. In general, expressing change relative to baseline can help describe the size and direction of change on a scale tied to each participant’s starting value. The registry specifies the mean as the summary measure and standard deviation as the measure of dispersion. The standard deviation describes how variable individual observations are around the mean; it is not, by itself, a measure of how precisely the mean has been estimated.

The endpoint description and analysis population are reported, but the numerical mean, standard deviation, and other results for this endpoint are not reported in the registry record. The direction the investigators regarded as improvement is stated, but the observed direction and size of change cannot be determined from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as percent change in ALP from baseline to Week 12, summarized by a mean with standard deviation. The endpoint is continuous: it can take values across a scale rather than being limited to categories. A mean provides a summary of the group’s observed values, while the standard deviation describes their spread. These statistics answer different questions. A small standard deviation would indicate less dispersion around the mean, but would not by itself show that the mean is estimated precisely; precision also depends on information such as the number of observations and the analysis method.

General statistical explanation: A confidence interval, when reported, gives a range of values compatible with the data and the interval’s stated method. It helps communicate uncertainty around an estimate; it is not a range containing a known true value with certainty. The registry record does not report a confidence interval for the primary endpoint. It also does not report a p-value or a test used to assess the endpoint. Without such results, the mean change’s precision and any inferential claim cannot be assessed from the registry information.

The primary endpoint is a change from baseline, not a comparison between independent treatment groups. In general, a before-and-after measure can be useful for describing how observations differ over time within a treated group. However, those changes alone do not show what would have happened over the same period without treatment. A concurrent control group can help address that question, but this registry lists a single-group model and no masking. The result, if reported, would therefore need to be interpreted as a within-group observation rather than a randomized between-group treatment contrast.

The registry defines the primary analysis population as the ITT Population, consisting of all subjects who received at least one dose of HTD1801. The label does not establish how every possible analysis issue was handled. Details such as the treatment of participants with missing Week 12 values, the method for calculating percent change, and whether any adjustments were applied are not reported in the registry record.

General statistical explanation: Missing outcome data can affect an estimate if the participants with observed follow-up differ systematically from those without it. Analysis methods may make different assumptions about missingness, so reporting the number and pattern of missing observations and the analysis approach is important. The registry record does not report those details for the primary endpoint. No particular missing-data method or assumption can therefore be attributed to this study based on the posted information.

The registry lists a mean and standard deviation as the primary summary, but does not state whether additional summaries or sensitivity analyses were used. It reports one analysis in the record’s analysis information, without providing further statistical-plan details. Whether the endpoint was analyzed with a particular model, whether covariates were included, and how any assumptions were checked are not reported in the registry record.

Multiple outcomes raise a separate interpretive issue. The registry lists a primary endpoint and secondary outcomes covering biochemical measures, GLOBE score, and pruritus. When researchers evaluate multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately without an appropriate strategy. In general, multiplicity procedures can control or otherwise address this issue, but the registry record does not report a multiplicity plan, adjustment, or hierarchy for interpreting secondary results. The numerical secondary results are also not reported in the registry record.

The record includes sample-size planning illustrations based on an observed effect, with assumptions describing two-sided significance, equal allocation between two arms, and a normal approximation. It characterizes these as planning illustrations rather than the trial’s own design. Such calculations concern hypothetical future planning under their stated assumptions; they are not observed power and do not supply missing outcome evidence. The registry does not report the trial’s own sample-size justification. Since the numerical illustrations and primary effect estimate are not reported in the registry information used for this analysis, their numerical implications cannot be described.

General statistical explanation: Over-dispersion occurs when variability is greater than a model assumes. If ignored, standard errors and uncertainty estimates can be misleading. That issue is relevant only when a suitable model and data structure warrant its assessment; the registry does not report a model or an over-dispersion assessment for this endpoint. It would be inappropriate to assert that over-dispersion occurred or that a particular correction was used.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("HTD1801 1000 mg BID")
n   <- c(20)
m   <- c(-7.7)
sp  <- c(23.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  HTD1801 1000 mg BID  20  -7.700  23.300  -18.605  3.205

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies ALP percent change as the primary endpoint and lists secondary outcomes covering total bilirubin, GGT, total cholesterol, IgM, GLOBE score, and pruritus VAS. It does not report a multiplicity strategy, such as an adjustment for multiple testing or a hierarchy governing how secondary outcomes were interpreted. The registry record also does not report numerical results for those secondary outcomes. Without the analysis plan and results, it is not possible to assess how multiplicity was handled or to interpret a collection of outcome tests.

The primary analysis population is described as the ITT Population, including all subjects who received at least one dose of HTD1801. The record does not report how many participants contributed observations at each endpoint time, whether any Week 12 values were missing, or how missing values were handled. It also does not report whether the analysis used any imputation, a model accommodating incomplete data, or a sensitivity analysis. No particular method or missing-data assumption should be inferred.

The registry gives enrollment of 24 and defines the analysis population, but those details do not reveal the availability of primary endpoint observations. In general, missingness can affect interpretation if the availability of measurements is related to participants’ outcomes or characteristics. Knowing the analysis population’s definition alone does not show whether that concern arose or how it was addressed.

The registry record does not report a statistical analysis plan, interim analyses, or a sample-size justification for this study. The planning illustrations described in the record are not a substitute for those design details or for observed endpoint results.

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: covid-19 pneumonia (4.2%).

The safety record lists the HTD1801 1000 mg BID group with 24 participants at risk for the serious-event summary and 1 affected. It lists 24 at risk for the other adverse-event summary and 23 affected. The deaths count is 0. These are descriptive counts from the registry record; they do not provide a comparison with an untreated or alternative-treatment group.

The record identifies COVID-19 Pneumonia as a top serious adverse event term, with 4.2% listed beside it. The information does not establish the event’s relationship to treatment, its timing, severity details beyond its placement among serious terms, or the circumstances for any affected participant. Those details are not reported in the registry record.

In general, an at-risk denominator describes the group being considered for an event summary, while the affected count describes participants recorded as having an event. Serious events and other adverse events are separate summaries and should not be conflated. These counts do not by themselves quantify comparative risk or determine causation. The study is open-label and single-group, so the posted safety figures are descriptive rather than a controlled safety comparison.

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

The registry record establishes that a Phase 2, open-label, single-group study evaluated HTD1801 in adults with PBC who had an inadequate response to standard therapy. It specifies a 12-week study purpose focused on safety and tolerability, a primary endpoint of percent change in ALP from baseline to Week 12, and a primary analysis population defined by receipt of at least one dose. It also provides descriptive adverse-event counts.

The registry description says a reduction in ALP represents an improvement, but the numerical primary endpoint result is not reported in the registry record. Therefore, the posted information does not establish whether ALP increased or decreased, how large any change was, or how precisely it was estimated. The secondary outcome results are likewise not reported. A statement about the intended meaning of an endpoint must not be mistaken for a reported result.

Even if a within-group change were available, a single-group open-label design would not provide the same evidence as a randomized comparison with a concurrent control. In general, a baseline comparison cannot distinguish intervention-associated change from other influences on change over time. The design also does not support a direct estimate of how outcomes would differ under another treatment.

The safety counts describe events recorded among participants in the treatment group, including the listed count of serious events, other adverse events, and deaths. They do not by themselves determine whether an event was caused by HTD1801 or how the safety profile compares with another option. The record’s listed COVID-19 Pneumonia term is a descriptive entry, not a causal conclusion.

Overall, the registry information supports understanding the question and design, but the unreported outcome values leave the central efficacy interpretation unresolved. It does not establish that HTD1801 works or does not work, and it does not establish comparative benefit or harm.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a clinical question and an outcome can be clearly specified even when registry results do not allow an estimate of the outcome itself. The record identifies the target population, intervention, time point, primary measure, summary statistic, and analysis population. Those elements help readers understand what the investigators intended to evaluate.

It also illustrates the interpretive limits of a single-group, open-label design. A change from baseline can describe the course of a measure among treated participants, but without a concurrent control it cannot isolate the contribution of treatment from other explanations for change over time. This distinction is important when interpreting biological measures and patient-reported outcomes alike.

The primary endpoint’s interpretation is directionally stated: a reduction in ALP represents improvement. Yet the registry does not report the numerical primary result. This makes the distinction between a defined endpoint and an observed finding especially important. A planned measurement, a favorable direction, or a sample-size planning illustration is not a substitute for a posted estimate and its uncertainty.

The record also shows why safety summaries require context. Counts of affected participants and a listed serious event term can describe what was recorded, but a single-group registry summary cannot establish comparative risk or causality. Details about analysis populations, missing observations, multiplicity, and statistical methods further shape how results should be interpreted; these are not reported 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 principal limitation for interpreting outcomes is that the registry record does not report the numerical result for the primary ALP endpoint. The mean percent change and standard deviation are not available in the posted information, and the record does not provide a confidence interval or test result. Numerical results for the listed secondary outcomes are also not reported. As a result, neither the magnitude nor the precision of changes can be evaluated.

The study is open-label and single-group, with allocation marked NA and masking listed as none. There is no concurrent control group in the registry design. Thus, any within-group change would not provide a randomized estimate of the difference attributable to HTD1801 compared with another condition or treatment. The design also leaves open the possibility that factors other than the intervention could contribute to changes over time.

The registry does not report details needed to evaluate analysis choices, including the method for calculating the endpoint, handling of missing Week 12 measurements, use of adjustments or sensitivity analyses, or a multiplicity plan. It also does not report an interim-analysis plan or the trial’s own sample-size justification. These omissions limit assessment of statistical robustness and precision.

Safety information is descriptive. The record lists affected counts and a serious adverse event term, but it does not provide a controlled comparison or enough detail to infer causality. The posted record therefore supports a description of the study and selected safety counts, not a complete evaluation of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis — NCT04604652.
• Registry record last updated 2026-08-25; status last verified 2026-08.
• Results first posted 2024-04-24.
• 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

The registry describes NCT04604652 as a completed Phase 2, open-label, single-group study of HTD1801 (BUDCA) in adults with primary biliary cholangitis and an inadequate response to standard therapy. Enrollment is listed as 24. The intervention was HTD1801 250 mg tablets, dosed at 1000 mg BID with food. The stated study purpose was to evaluate safety and tolerability over 12 weeks.

The primary endpoint was percent change in ALP from baseline to Week 12, summarized as a mean with standard deviation. The primary analysis population included subjects who received at least one dose. The registry lists secondary biochemical, clinical-score, and pruritus outcomes, and reports descriptive safety counts, including 1 affected participant in the serious-event summary, 23 in the other adverse-event summary, and 0 deaths.

The numerical primary and secondary outcome results are not reported in the registry record. Consequently, the posted information describes the study design and measures but does not establish the observed ALP change or its precision.