PK Profile and Preliminary Efficacy of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PK Profile and Preliminary Efficacy of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia (NCT06135675), a randomized phase 1, phase 2 study. The primary outcome is Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs).

2. Clinical Question

The study also aimed to assess tolerability and pharmacokinetic characteristics and to preliminarily observe changes in blood ammonia and hepatic encephalopathy-related clinical symptoms and signs, neuropsychological indicators, and quality of life. The registry lists outcomes related to fasting venous blood ammonia, Number Connection Test A, Digital Symbol Test, quality of life, asterixis, clinical grade of hepatic encephalopathy, and blood-ammonia concentration-time curves. The main posted result described in the registry is a count of participants with adverse events, rather than a comparative estimate of efficacy.

3. Trial Design

This was a phase 1b/2a study recorded as randomized, double-masked, and sequential. The registry reports enrollment of 36 participants and a completed status. The study began on 2020-08-27, and primary completion was recorded as 2021-06-16. Further information about how randomization was carried out, what parties were masked, and how the sequential structure operated is not reported in the registry record.

Four groups are listed: TNP-2092 capsules at 100 mg twice daily, 300 mg twice daily, or 600 mg twice daily, and placebo. Each regimen was administered orally in the fed state twice daily for consecutive 14 days, with the last dose on the morning of Day 15. The listed group sizes were 8 participants for each active dose and 12 for placebo. These counts sum to the reported enrollment of 36.

The primary outcome was the number of participants with adverse events, assessed up to 17 days after the first dose. Its analysis population included subjects who received at least one dose. The record also lists 22 outcome measures and seven secondary outcomes, including measures of blood ammonia, neuropsychological test results, quality of life, asterixis, hepatic encephalopathy grade, and pharmacokinetic exposure.

The record identifies the sponsor as TenNor Therapeutics (Suzhou) Limited. Detailed eligibility criteria, allocation procedures, masking roles, dose-escalation or cohort-transition rules, and the protocol’s statistical analysis plan are not reported in the registry record. The sequential label alone does not establish how dose groups were ordered or what criteria governed movement between them.

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

Analysis population for the primary outcome, as defined in the registry: All subjects who have received at least one dose of study drug.

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 Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs), measured over Up to 17 days after the first dosing..

The primary endpoint counts participants who experienced at least one adverse event after receiving study drug. The assessment period was up to 17 days after the first dose, and the analysis population was all subjects who received at least one dose. In the posted results, the endpoint is expressed as a count of participants in each group.

The registry definition is deliberately broad: an adverse event is any untoward medical occurrence in a participant administered a drug, whether or not it has a causal relationship with that treatment. Thus, the endpoint describes events occurring during the defined observation period; it does not by itself establish that treatment caused an event. Nor does a participant count describe the number, duration, severity, or clinical importance of all events experienced by that participant.

General statistical context: a participant-level safety count is useful for describing how many people had at least one event, while separate event-level summaries can describe types or recurrence. These answer different questions. The registry’s primary endpoint is a safety and tolerability measure, not a direct measure of pharmacokinetic exposure, blood-ammonia change, or clinical benefit. Those topics appear among the study aims and secondary outcomes, but the posted primary result alone cannot answer them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is binary at the participant level: each person is counted as having experienced an adverse event or not, according to the recorded endpoint. The reported result is the number of participants with an event in each group, accompanied by the group size. It is not a count of all individual events. One participant may experience more than one event, but the primary participant count does not express that recurrence.

The endpoint definition includes any untoward medical occurrence after drug administration and does not require a causal relationship with treatment. That broad definition supports safety surveillance, but it means that the count should be interpreted as events observed during follow-up rather than events necessarily caused by the assigned intervention. The endpoint timeframe was up to 17 days after the first dose.

Why might a comparison be unavailable?

The registry marks a two-arm binary comparison as having values missing or not estimable. It reports no analysis records. Thus, the posted result supports description of the group counts but not an inferential comparison between a dose and placebo. No odds ratio, risk difference, risk ratio, confidence interval, or p-value is reported for the primary outcome. These quantities should not be reconstructed from the counts as if they were the sponsor’s planned analysis.

General statistical context: a comparative analysis needs a defined contrast and a method that accounts for the outcome type and study design. A confidence interval gives a range of values compatible with the data under the specified model and assumptions. A wide interval indicates imprecision; a narrow interval indicates greater precision conditional on those assumptions. A p-value addresses compatibility with a specified null model, not the probability that a treatment works. Neither quantity is available for this primary comparison in the registry result.

What does masking contribute?

The study is recorded as double-masked. In general, masking can reduce the influence of expectations on care, reporting, or assessment, depending on who is masked and how procedures are implemented. The registry does not report which participants or study personnel were masked, how masking was maintained, or whether masking was assessed. The designation therefore describes the recorded design classification, but it does not establish how masking operated in practice.

What does the sequential design label establish?

The record classifies the model as sequential and lists three dose groups and a placebo group. The label does not, by itself, specify cohort order, dose-escalation criteria, decision rules, or whether information from one group affected enrollment or treatment in another. Those details are not reported in the registry record and should not be assumed when interpreting the group counts.

How should planning calculations be read?

General statistical context: sample-size calculations depend on assumptions about the outcome, target effect, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not evidence that the trial was designed with that effect in mind, and it is not observed power. The registry record does not report the trial’s own sample-size justification. No numerical planning illustration is reported in the available record for interpretation.

General statistical context: over-dispersion matters when a count outcome varies more than the assumed model allows, because a model that understates variability can produce overly precise intervals or tests. The primary endpoint is a count of participants with an event, not a repeated-event count model; no over-dispersion analysis is reported. Methods for repeated events would require event-level information and assumptions not described for this primary result.

Finally, the record lists 22 outcome measures and seven secondary outcomes but no analysis records. It does not report the statistical methods used for secondary endpoints, the handling of repeated measurements, or a prespecified hierarchy of outcomes. These omissions limit independent assessment of how the planned outcome set relates to the posted safety findings.

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("TNP-2092 Capsules 100mg Twice Daily(BID)", "TNP-2092 Capsules 300mg BID", "TNP-2092 Capsules 600mg BID", "Placebo")
n      <- c(8, 8, 8, 12)
events <- c(6, 6, 7, 8)
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  TNP-2092 Capsules 100mg Twice Daily(BID)  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  TNP-2092 Capsules 300mg BID  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  TNP-2092 Capsules 600mg BID  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  Placebo  12  8  66.7  34.9  90.1  39.1  86.2  38.6  86.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, including seven secondary outcomes, but reports no analysis records. A multiplicity strategy—such as a hierarchy of outcomes or an adjustment for testing several hypotheses—is not reported in the registry record. Without such information and without posted analyses, it is not possible to assess how the study addressed the risk of false-positive findings across multiple outcomes. The secondary outcome list describes measures of interest; it does not establish that each was tested or that any result was statistically persuasive.

Missing-data methods are also not reported. The primary endpoint population is defined as all subjects who received at least one dose, but the record does not explain how incomplete adverse-event follow-up, withdrawals, or other missing observations were handled. The group sizes and event counts are posted, but they do not show whether all participants contributed complete observation over the endpoint timeframe.

The record does not describe analysis populations for the secondary outcomes, including whether they used all randomized participants, treated participants, or outcome-specific subsets. It also does not report imputation, sensitivity analyses, or rules for handling measurements that were unavailable or not evaluable. These details matter because conclusions can depend on who is included and how missing outcomes are treated. No assumptions about those procedures can be made from the posted counts alone.

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: gastrointestinal haemorrhage (8.3%).

The serious adverse event counts are 0 of 8 participants in the 100 mg group, 0 of 8 in the 300 mg group, 0 of 8 in the 600 mg group, and 1 of 12 in the placebo group. The record reports no deaths in any group. These are participant counts, not event rates adjusted for duration of exposure.

Gastrointestinal haemorrhage is listed as a serious adverse event term at 8.3%. The registry’s term listing does not specify the group for that term. The one participant with a serious adverse event is reported in the placebo group, but the term-level entry should not be taken to identify that participant’s group unless the record explicitly links them.

General statistical context: serious-event counts describe events observed in the study and are not, by themselves, proof of causation or proof that an event cannot occur in another group. With few participants, zero observed serious events is not evidence that the underlying risk is zero. The short listed dosing period and the endpoint’s follow-up window also define the scope of these observations; longer-term safety is not established by these counts.

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

The posted results describe adverse events among participants who received study drug during the stated follow-up period. They show 6 participants with an adverse event in each of the two lower-dose groups, 7 in the 600 mg group, and 8 in the placebo group. Serious adverse events were reported in 1 participant in the placebo group and none in the active-dose groups; no deaths were reported.

These findings are descriptive. There is no reported inferential comparison for the primary endpoint, so the record does not quantify the uncertainty around a treatment-versus-placebo difference. The observed counts cannot, on their own, establish that one regimen has a higher or lower underlying event risk. The endpoint definition also does not imply that every event was caused by treatment.

The study aimed to examine pharmacokinetics and preliminarily observe blood ammonia, hepatic encephalopathy-related measures, neuropsychological indicators, and quality of life. Those aims should not be confused with results: the registry lists outcome measures but reports no analysis records. The posted safety counts therefore do not establish findings for those clinical or laboratory outcomes.

General statistical context: absence of a reported significant difference is not the same as evidence of equivalence, and a small observed difference is not automatically meaningful. Equivalence or non-inferiority conclusions require a prespecified margin, an appropriate analysis, and adequate precision. Such conclusions are not reported for this study. The registry record also does not report a sample-size justification, so the planned ability to detect a particular difference cannot be assessed.

Overall, the registry supports a narrow reading: it documents the group sizes and observed participant counts for adverse events and serious adverse events over a short study period. It does not support a definitive comparative efficacy conclusion or a precise estimate of comparative safety.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a descriptive safety result and a comparative treatment effect. The registry posts participant counts in each group, which are useful for understanding what was observed, but it does not post an analysis for a two-arm binary comparison. Without an estimate and its uncertainty, readers cannot judge the precision of differences between groups from the registry record.

The study also illustrates why outcome definitions matter. The primary endpoint counts participants with any adverse event, regardless of whether the event was attributed to treatment. That endpoint answers a broad safety-surveillance question; it does not summarize event severity, recurrence, or causality. Serious adverse events and deaths are reported separately, and should not be conflated with the all-adverse-event endpoint.

The multiple listed outcomes raise a further statistical issue. The registry identifies 22 outcome measures and seven secondary outcomes, but gives no analysis records or reported multiplicity approach. Without analysis results and a testing strategy, the outcome list cannot be treated as a collection of confirmed findings.

Finally, the randomized, double-masked classification and the recorded sequential model provide useful design context, but the registry does not describe the operational details of these features. Recognizing what a record does and does not report is central to sound interpretation: the observed counts are available, while the comparative precision, analysis procedures, and results for other outcomes are not.

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 listed groups are small: 8 participants in each active-dose group and 12 in the placebo group. This limits how much detail the counts can provide about uncommon events and makes the observed group pattern sensitive to a small number of participants. The registry does not report confidence intervals or another measure of precision for the primary outcome.

The primary endpoint is a broad participant-level count. It does not report the number of individual events per participant, their duration, severity, timing, or causal assessment. Serious-event counts add separate safety information, but the listed serious-event term is not linked to a group in the term listing. No deaths were reported, but the observation period and study size do not establish the absence of risk beyond the recorded follow-up.

The study is described as randomized, double-masked, and sequential, but details of randomization, masking, and sequential decision procedures are not reported in the registry record. Eligibility criteria beyond liver cirrhosis with hyperammonemia, participant characteristics, baseline balance, and adherence information are also not reported. These omissions limit assessment of comparability and generalizability.

The registry reports seven secondary outcomes and 22 outcome measures but no analysis records. Statistical methods, multiplicity control, missing-data handling, and outcome-specific analysis populations are not reported. The sample-size justification is not reported either. In consequence, the available record does not support evaluation of statistical power, the precision of comparative effects, or the robustness of findings across outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PK Profile and Preliminary Efficacy of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia — NCT06135675.
• Registry record last updated 2025-04-25; status last verified 2025-04.
• Results first posted 2024-05-10.
• 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 record describes NCT06135675, a completed phase 1b/2a study of TNP-2092 capsules in liver cirrhosis patients with hyperammonemia. It was recorded as randomized, double-masked, and sequential, with enrollment of 36 participants. Groups received 100 mg, 300 mg, or 600 mg of TNP-2092 twice daily, or placebo, in the fed state for consecutive 14 days, with the final dose on the morning of Day 15.

The primary endpoint counted participants with adverse events up to 17 days after the first dose. Posted counts were 6, 6, and 7 participants in the three active-dose groups and 8 in the placebo group. Serious adverse events were reported in 0, 0, 0, and 1 participant, respectively; no deaths were reported. The record lists secondary outcomes concerning blood ammonia, neuropsychological measures, quality of life, hepatic encephalopathy, and pharmacokinetics, but reports no analysis records. Comparative statistical results and the trial’s own sample-size justification are not reported in the registry record.