Phase 1 Study of PBTZ169: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1 Study of PBTZ169 (NCT03036163), a randomized phase 1 study. The primary outcome is Incidence of Drug-related Adverse Events [Safety and Tolerability].

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label, prospective, noncomparative study of PBTZ169 in healthy volunteers. Its stated purpose was to assess safety, tolerability and pharmacokinetics after single and multiple oral administration in increasing doses while fasting. The registry lists randomized allocation and a parallel model, but does not report how randomization was performed or how the parallel cohorts were formed. The study began in 2016-01, had primary completion in 2016-09 and is marked completed.

Five cohorts received one oral dose: 40 mg, 80 mg, 160 mg, 320 mg or 640 mg. The registry describes 6 male healthy volunteers in each of these cohorts. Two further cohorts received once-daily administration for 14 days: 320 mg or 640 mg, with 5 male healthy volunteers in each. The capsules were 40 mg each. All participants were described as fasted, and masking was listed as none.

The registry enrollment is 40. The design is explicitly noncomparative, with no placebo or other control regimen described. Although the dose groups permit descriptive examination of posted outcomes across regimens, the record does not describe a prespecified statistical comparison among cohorts. It also does not report allocation details, dose-escalation decision rules, or whether the next dose depended on review of earlier safety findings. Those design details are not reported in the registry record.

The primary endpoint was the number of participants with drug-related adverse events, assessed through 14±1 days after drug administration up to the last visit. The safety population was defined as subjects who received at least one dose. Secondary outcomes included pharmacokinetic measures such as peak plasma concentration, time to maximum concentration, area under the concentration-time curve, half-life, mean retention time, clearance, volume of distribution and elimination constant. Numerical results for these secondary measures are 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.

Only the first 6 of 7 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety population: subjects who received at least one dose of PBTZ169. The population was used for the analysis and evaluation of the demographic and other baseline data and all safety parameters including AEs, physical examination, evaluation of the vital signs, previous and current therapy, ECG, all laboratory tests

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

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Drug-related Adverse Events [Safety and Tolerability], measured over 14±1 days after the drug administration (up to last visit time point).

The primary endpoint counts participants for whom an adverse event was considered related to PBTZ169. It is a safety and tolerability measure, not a measure of tuberculosis outcomes or treatment benefit. The registry specifies that the count applies to the safety population, defined as subjects who received at least one dose, and gives a follow-up timeframe of 14±1 days after drug administration, up to the last visit time point.

A participant count is a binary-outcome summary: each person either had at least one event meeting the endpoint definition or did not. It does not count the total number of event episodes, describe the nature or severity of each event, or show when events occurred. The record’s description says that the relationship to the test drug was noted, but does not report who assessed relatedness, the rules used to classify it, or whether this judgment was blinded. Because the study was open-label, participants and study staff were not masked according to the registry.

This kind of endpoint is used in early-phase studies to describe observed tolerability during the specified observation period and across studied dose regimens. It can identify a pattern worth further evaluation, but small cohorts and short follow-up limit how precisely uncommon events can be characterized. The posted primary counts are 2 in Cohorts 1 and 2, 1 in Cohorts 3, 6 and 7, and 0 in Cohorts 4 and 5. The registry does not report confidence intervals or a formal statistical test for these counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a binary endpoint records whether each participant experienced an event meeting a defined criterion. The primary endpoint is a participant count for drug-related adverse events. The registry posts the number affected and the cohort size, rather than a model-based estimate or a test of differences. That format is directly interpretable as a description of the observed participants, but the counts alone do not quantify uncertainty or establish that cohort outcomes differ beyond chance variation.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified method. It helps distinguish a precise estimate from one compatible with a broad range of values. The registry record does not report confidence intervals for the primary endpoint, so the precision of each cohort’s event frequency cannot be evaluated from interval estimates. No interval can be reconstructed without choosing a method, and doing so would add an analysis not reported in the record.

What can be learned from these cohorts?

The groups are small: the single-dose cohorts each list 6 participants, and the repeated-dose cohorts each list 5. In general, counts from small groups can change noticeably if only a few participants have or do not have an event. This makes the observed results useful as a description of these enrolled volunteers but limits their precision and their ability to characterize uncommon events. The study has no placebo or untreated arm described and is called noncomparative. Therefore, the cohort counts are not a randomized treatment-versus-control estimate.

The registry labels allocation as randomized, but does not explain the randomization method, sequence generation, allocation concealment or assignment procedures. General principles of randomized studies depend on those details to understand how allocation may reduce systematic differences between groups. Without the details, and given the stated noncomparative design, the allocation label should not be read as evidence of a fully specified head-to-head comparison. The record also does not report a prespecified statistical model for the primary endpoint.

Why is dose and schedule important?

General interpretation requires attention to the regimen being studied. A single administration and once-daily dosing for 14 days differ in exposure pattern, so their safety observations are not interchangeable. The study included single doses from 40 mg through 640 mg and repeated-dose regimens of 320 mg and 640 mg. A numerical pattern across these groups would still be descriptive unless the analysis and comparison were specified. The registry does not report dose-escalation criteria or rules for making decisions between cohorts.

The primary endpoint specifies events for which a relationship to the test drug was noted. In general, relatedness classification requires a judgment using some clinical or protocol-defined approach. The record does not describe the criteria, assessor, adjudication process or whether a standardized coding system was used. Open-label conduct can also mean that treatment knowledge is available to participants and study staff; the registry lists masking as none. The record does not explain how this might have been handled in the assessment of events.

How should planning calculations be read?

General sample-size calculations use assumptions about the outcome, statistical test, significance level, allocation and effect one aims to detect. The planning assumptions described for this study use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with target effects expressed as fractions of an observed effect. These are planning illustrations, not observed power and not evidence of the actual design rationale. The registry does not report the trial’s own sample-size justification, a formal power calculation, or a statistical plan. Numerical planning outputs are not reported in the registry record.

For a binary endpoint, a planning calculation also depends on the event frequency assumed in the comparison. In general, when observed counts come from small cohorts, calculations anchored to an observed effect can be unstable: the effect estimate may itself be imprecise. A planning illustration cannot show how likely the completed study was to detect an effect, nor can it remedy the absence of a comparator. No claim about adequate power should be based on such an illustration.

What can be said about pharmacokinetics?

The record names peak plasma concentration, time to maximum concentration, area under the concentration-time curve, plasma half-life, mean plasma retention time, total clearance, volume of distribution and elimination constant as secondary outcomes. These are standard types of pharmacokinetic measures that describe concentration, timing, exposure and drug disposition in general. However, their numerical results, variability estimates and analysis methods are not reported in the registry record. The posted safety counts cannot substitute for those pharmacokinetic results.

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("Cohort 1", "Cohort 2", "Cohort 3", "Cohort 4", "Cohort 5", "Cohort 6")
n      <- c(6, 6, 6, 6, 6, 5)
events <- c(2, 2, 1, 0, 0, 1)
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  Cohort 1  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Cohort 2  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Cohort 3  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Cohort 4  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 5  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 6  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple dose regimens and a set of secondary pharmacokinetic outcomes in addition to the primary safety endpoint. When many outcomes or comparisons are tested, general statistical practice considers multiplicity because repeated testing can increase the chance of at least one apparently notable result arising by chance. The registry record does not report a multiplicity strategy, a hierarchy of hypotheses, or formal tests across cohorts or outcomes. It also reports no analyses for the posted results. Therefore, the event counts should be read descriptively rather than as findings from a declared family of hypothesis tests.

The record identifies a safety population comprising subjects who received at least one dose. It says this population was used for analysis and evaluation of demographic and other baseline data and safety parameters, including adverse events, physical examination, vital signs, previous and current therapy, and ECG. The registry does not describe other analysis populations, exclusions from the safety population, or analysis rules for participants who discontinued or missed visits. Missing-data handling is not reported in the registry record.

That absence of information does not establish that data were missing, nor does it establish that all participants completed follow-up. It means the posted record does not explain how incomplete safety observations, if any, were handled. The primary endpoint timeframe runs through 14±1 days after drug administration up to the last visit, but procedures for censoring, imputation or incomplete follow-up are not reported. The statistical analysis plan, including any prespecified treatment of missing observations and multiplicity, is not reported in the registry record.

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 non-serious adverse event terms

The serious-adverse-event figures report 0 affected participants in every cohort. Each single-dose cohort lists 6 participants at risk; each repeated-dose cohort lists 5. Deaths are also reported as 0 in all cohorts. These counts describe what was recorded among the enrolled volunteers during the study’s observation period; they are not proof that serious events or deaths could not occur.

Serious adverse events and other adverse events are separate categories in the registry safety information. The other-event counts are 2 in Cohorts 1 and 2, 1 in Cohort 3, 0 in Cohorts 4, 5 and 6, and 1 in Cohort 7. Those figures should not be confused with the primary endpoint, which is specifically the number of participants whose adverse events were noted as related to PBTZ169. The record does not provide event descriptions, severity grades for non-serious events, timing, or participant-level overlap among event categories.

In general, zero observed serious events in small cohorts still leaves uncertainty about uncommon harms. The registry does not report confidence intervals for these counts or longer-term follow-up beyond the specified study period. The posted safety information is therefore a record of events observed in these groups, not a comprehensive estimate of risk.

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

The posted results describe safety observations in healthy volunteers receiving single or repeated oral doses of PBTZ169 while fasting. For the primary endpoint, the record lists drug-related adverse-event counts by cohort, with values ranging from 0 to 2 participants. It also reports zero serious adverse events and zero deaths in each cohort. These are the observed counts, not estimates adjusted for participant characteristics or comparisons against a control group.

The results do not establish that the regimens are equivalent or that one regimen is safer than another. The study is described as noncomparative, and no formal statistical comparisons are reported. Differences in small cohort counts can be imprecise, and the registry does not provide confidence intervals or hypothesis tests to quantify uncertainty. A zero count in a cohort means no such event was recorded in that group during the reported observation; it does not establish zero risk.

The results also do not establish safety in people with tuberculosis. The participants were healthy volunteers, and the endpoint concerns adverse events rather than clinical outcomes of tuberculosis. Although pharmacokinetic outcomes are listed, their numerical results are not reported in the registry record. The posted results therefore do not support conclusions about drug exposure, concentration patterns or pharmacokinetic differences among regimens.

More broadly, a Phase 1 safety study of this kind provides a bounded description of early exposure, in the population and follow-up period recorded. It cannot determine whether PBTZ169 prevents or treats tuberculosis, and the record gives no efficacy endpoint results. The counts should be interpreted in that limited context rather than as a general statement about outcomes in other populations, longer use or other conditions.

14. Why This Trial Matters Statistically

This study is statistically useful as an example of the difference between describing observations and estimating comparative effects. Its primary outcome is a participant count within each cohort. That format makes the observed data easy to state, while the small groups and noncomparative design constrain how much can be inferred about differences among doses. The registry’s randomized-allocation label does not replace a clearly described comparator or a reported analysis plan.

It also illustrates why event counts need context. A zero count can appear reassuring at first glance, but in general its meaning depends on how many people were observed, for how long, and how completely events were assessed. Here, cohorts are small and follow-up is specified as 14±1 days after administration up to the last visit. The record does not provide interval estimates or details about missing observations, so precision and completeness cannot be fully assessed.

The trial separates safety and tolerability from pharmacokinetics, listing several concentration and disposition outcomes. Yet numerical results for those outcomes are not present in the registry record. This distinction matters: an endpoint list indicates what was intended for assessment, not what results are available for interpretation.

Finally, planning calculations based on an observed effect are not the same as evidence of observed power or proof that a design was adequate. In general, sample-size planning depends on assumptions set before a study and on the intended comparison. The registry does not report its own sample-size justification or statistical plan. Recognizing these boundaries helps keep a small early-phase safety description separate from stronger claims that would require fuller data and a specified comparative analysis.

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 study enrolled healthy male volunteers, so its safety findings do not directly describe people with tuberculosis or other populations. The registry reports small cohort sizes, and the follow-up window for the primary endpoint is limited to 14±1 days after drug administration up to the last visit. Longer-term outcomes are not reported in the registry record.

The design is stated to be open-label and noncomparative. No placebo or untreated comparison group is described, and no inferential comparison among the dose cohorts is reported. The registry labels allocation randomized, but the allocation method and procedures are not reported. Dose-escalation criteria and any safety review rules are also not reported, so the way cohorts were sequenced or governed cannot be evaluated from the record.

The primary results are counts without confidence intervals, p-values or a reported statistical model. The record does not explain how drug relatedness was determined or whether events were independently adjudicated. It provides no detailed event descriptions or participant-level event data. The registry also does not report missing-data procedures, follow-up completion, or analysis rules for discontinuations.

Although pharmacokinetic outcomes are named, their numerical findings are not reported in the registry record. The sample-size justification, statistical analysis plan, and any prespecified multiplicity approach are also not reported. These omissions limit assessment of precision, analysis choices and the scope of conclusions that can be drawn from the posted counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1 Study of PBTZ169 — NCT03036163.
• Registry record last updated 2020-04-13; status last verified 2020-03.
• Results first posted 2020-04-13.
• 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 a completed, Phase 1, open-label, prospective, noncomparative study of PBTZ169 in fasted healthy volunteers. Enrollment was 40. Participants received single doses from 40 mg through 640 mg or once-daily dosing of 320 mg or 640 mg for 14 days. The primary endpoint counted participants with adverse events considered related to PBTZ169 through 14±1 days after administration, up to the last visit.

Posted drug-related adverse-event counts were 2 in Cohorts 1 and 2, 1 in Cohorts 3, 6 and 7, and 0 in Cohorts 4 and 5. Serious adverse events and deaths were reported as 0 in every cohort. The registry lists pharmacokinetic secondary outcomes, but their numerical results are not reported in the registry record. Formal statistical comparisons, confidence intervals, the statistical analysis plan, missing-data procedures and the trial’s sample-size justification are also not reported.