A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB) (NCT01859923), a non-randomized phase 2 study. The primary outcome is Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, non-randomized, parallel-group study sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. The registry lists an enrollment of 37 and a completed status. The recorded study start was 2013-07-20, and primary completion was 2020-01-13. Participants were organized into four age groups, with treatment formulation and dose described according to age. The registry record does not report random assignment, masking, or a concurrent control group; the study is explicitly listed as non-randomized and unmasked.

All groups received delamanid alongside an optimized background regimen of other anti-tuberculosis drugs. For participants 12 to 17 years old, the adult formulation was 100 mg twice daily; for those 6 to 11 years old, it was 50 mg twice daily. Participants 3 to 5 years old received 25 mg of the pediatric formulation twice daily. Participants from birth to 2 years old received the pediatric formulation for 182 days, with dose based on body weight at baseline. The registry record does not report the complete dose details for this youngest group in the study description.

The age-specific delamanid regimens extended up to Day 182, while the background regimen continued up to Day 365. The primary outcome timeframe also extended from the first dose through the end of post-treatment follow-up, up to Day 365. This distinction matters when interpreting the observation period: the primary safety outcome was not limited to the period of delamanid administration. No further details about visit schedules, treatment adherence, or protocol deviations are reported in the registry record.

Because allocation was not randomized and there was no like-for-like control arm, comparisons among age groups cannot isolate an age effect or a treatment effect. The groups differ by age and dosing regimen, and all received the background regimen. The registry record does not report a formal comparative design or adjusted between-group analysis.

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: Pediatric participants with a diagnosis of multidrug-resistant tuberculosis (MDR-TB) who were on therapy with an optimized background regimen (OBR) of anti-tuberculosis drugs and completed study 242-12-232 (NCT01856634) were enrolled in this extension study 242-12-233 to receive delamanid based on the participant's age and weight.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

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: The Safety Sample included participants who received any amount of investigational medicinal product (IMP) in this study, regardless of any protocol deviation or violation.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE), measured over From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365).

The primary endpoint is the number of participants with at least one treatment-emergent adverse event (TEAE). An adverse event is an untoward medical occurrence during a clinical trial and does not necessarily have a causal relationship with treatment. A TEAE is defined in the registry as an adverse event occurring after administration of the investigational medicinal product.

The outcome counts participants, rather than counting every event separately. A participant with multiple qualifying events is therefore represented in the endpoint as a participant who had at least one TEAE. This type of measure is used to describe how many participants experienced an event during a defined observation period. It does not, by itself, show how many events occurred, how severe or prolonged they were, or whether study treatment caused them.

The primary safety timeframe runs from the first dose through the end of the post-treatment follow-up period, up to Day 365. The safety population is defined as participants who received any amount of investigational medicinal product in this study, regardless of protocol deviation or violation. Although the endpoint is specified, the registry record does not report its numerical result or a statistical analysis of that result. It therefore does not establish a rate, a confidence interval, or a comparison with another treatment group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical distinctions help interpret the registry information. The study is non-randomized and open-label. In general, random allocation helps balance measured and unmeasured participant characteristics across comparison groups, while masking can reduce some forms of assessment or reporting bias. Neither feature is present in this study according to the registry record. The age groups are therefore descriptive cohorts, not randomized treatment arms. Their differences in age and dose formulation mean that a direct contrast between their outcomes would not isolate a single factor.

What does a participant count measure?

The primary endpoint is a count of participants with at least one TEAE. This is different from a count of all adverse-event episodes: multiple events in one participant do not create multiple participants in the endpoint. It is also different from an event rate over person-time, which would incorporate how long participants were observed. The registry specifies the endpoint timeframe but does not report an event rate, a participant-level result, or an analysis of time to first event. Thus, the endpoint definition alone does not provide a numerical risk estimate.

For general statistical interpretation, a confidence interval describes a range of values reasonably compatible with the data under the statistical model used. Its width reflects precision as well as the amount of information in the data. No confidence interval for the primary TEAE outcome is reported in the registry record, so the precision of that outcome cannot be assessed from the record. The descriptive serious-event counts also do not include reported confidence intervals.

Why does the comparison structure matter?

A comparison between randomized groups can, under suitable conditions, support an estimate of the effect of assignment to one intervention rather than another. This trial does not have that structure. All participants received delamanid with an optimized background regimen, while the age cohorts received age-specific formulations or doses. Observed differences across cohorts may reflect differences in age, treatment details, participant characteristics, or chance. A statistical adjustment could sometimes account for measured differences, but the registry record does not report an adjusted analysis, and adjustment cannot by itself create the protection against confounding that random allocation provides.

The registry lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is described as a stated fraction of the observed effect. These assumptions describe a hypothetical planning exercise, not the actual design of this non-randomized study. Equal allocation between two arms is not a description of the four age groups, and the registry record does not report that this planning exercise determined the study enrollment. Any sample-size values in such a planning exercise are illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. The registry record does not report a sample-size justification for the trial itself.

How should event categories be read?

Serious adverse events and other adverse events are distinct categories in the registry results. A serious-event count describes how many participants were recorded in that category; it does not convey all event details, such as duration, timing, recurrence, or attribution to study treatment. General explanations of over-dispersion apply when observed count variability exceeds what a chosen count model expects. Over-dispersion can affect standard errors and the reliability of model-based inference. However, the primary endpoint is a participant count with at least one event, and the registry record does not report a count model, a dispersion estimate, or an inferential analysis. It would not be appropriate to assume that a particular model was used.

The registry’s description defines the safety population as participants who received any amount of investigational medicinal product, regardless of protocol deviation or violation. This is a population definition, not a statement that every enrolled participant contributed to every outcome. Outcome-specific denominators can differ if eligibility, exposure, or available observations differ. The registry record does not report the analyzed denominator for the primary TEAE outcome, nor details of outcome-specific exclusions or missingness.

Finally, the presence of several listed outcomes raises the general issue of multiplicity. When many outcomes are tested, the chance of at least one apparently unusual result can increase if each test is interpreted separately without accounting for the number of tests. The registry record does not report a multiplicity adjustment, a testing hierarchy, or analyses for these outcomes. No claim about the statistical significance of secondary outcomes can be made from the outcome list alone.

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("Group 1: 12 to 17 Years of Age", "Group 2: 6 to 11 Years of Age", "Group 3: 3 to 5 Years of Age", "Group 4: Birth to 2 Years of Age")
n      <- c(7, 6, 12, 12)
events <- c(7, 6, 12, 12)
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  Group 1: 12 to 17 Years of Age  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Group 2: 6 to 11 Years of Age  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Group 3: 3 to 5 Years of Age  12  12  100.0  73.5  100.0  75.8  100.0  75.3  99.8
ARM  Group 4: Birth to 2 Years of Age  12  12  100.0  73.5  100.0  75.8  100.0  75.3  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary TEAE endpoint and secondary measures involving QTcB, pharmacokinetic and pharmacodynamic relationships, treatment outcome, chest x-ray findings, tuberculosis signs and symptoms, sputum culture conversion, and palatability. Listing several outcomes creates a general multiplicity concern: when many statistical tests are conducted, interpreting each in isolation can increase the chance of a false-positive finding. The registry record does not report a prespecified hierarchy, a family of primary hypotheses, or an adjustment for multiplicity. It also reports no analyses, so the record does not establish which outcomes were tested or how any results were interpreted.

The record defines the safety population as participants who received any amount of investigational medicinal product, regardless of protocol deviation or violation. It does not report the number included in the primary endpoint analysis, outcome-specific denominators, or how missing observations were handled. The registry record does not report whether missing data occurred, the reasons for any missingness, or any imputation or sensitivity-analysis methods. These absences prevent assessment of how missing outcome information might affect the reported results.

Likewise, the registry record does not report an analysis plan, interim analyses, stopping rules, or a sample-size justification for the trial. These details should not be inferred from the stated planning illustration, which is described as a hypothetical calculation based on an observed effect rather than the trial’s own design. Without reported analysis methods and outcome results, it is not possible to assess model assumptions, multiplicity control, or the robustness of estimates.

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: pneumonia (16.7%), non-hodgkin's lymphoma (16.7%), immune thrombocytopenic purpura (8.3%), lower respiratory tract infection (8.3%), oral candidiasis (8.3%).

The serious adverse event counts are reported by age group. The registry lists 0 of 7 participants in Group 1, aged 12 to 17 years; 1 of 6 in Group 2, aged 6 to 11 years; 2 of 12 in Group 3, aged 3 to 5 years; and 5 of 12 in Group 4, from birth to 2 years, as affected. The registry also lists deaths of 0, 0, 1, and 1 for those groups, respectively. These are descriptive counts and should not be read as a randomized comparison. The groups differ in age and dosing regimen, and the registry record does not report an analysis comparing their serious-event experience.

The listed serious adverse event terms include Pneumonia and Non-Hodgkin's lymphoma at 16.7% each, and Immune thrombocytopenic purpura, Lower respiratory tract infection, Oral candidiasis, and Vulvovaginal candidiasis at 8.3% each. The registry information does not report the denominator or age-group attribution for these term percentages. They should therefore be read as registry-listed percentages, not as directly comparable group-specific risks. Seriousness also does not imply causation: an adverse event may occur during a trial without being caused by the investigational treatment. The primary TEAE result itself is not reported in the registry record, and serious events are not interchangeable with all treatment-emergent adverse events.

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

The record establishes that a pediatric Phase 2 study was conducted to assess safety, tolerability, pharmacokinetics, and efficacy of delamanid with an optimized background regimen. It specifies age-based dosing descriptions, a treatment period extending up to Day 182 for delamanid, and a background regimen continuing up to Day 365. It also defines a primary safety outcome based on whether participants experienced at least one TEAE during follow-up. These details explain what the study set out to assess; they are not evidence of a particular treatment effect.

The serious-event counts provide descriptive information for the four age groups. They do not establish that one age group had higher underlying risk, or that age or dose caused the observed pattern. The groups were not randomized, and there was no like-for-like comparator. The reported counts also do not convey event timing, duration, severity beyond the serious classification, or treatment attribution. The listed serious-event term percentages have no stated denominator or age-group attribution in this record, which limits their interpretation.

The record does not report the numerical primary TEAE result, confidence intervals, p-values, or comparative analyses. It also does not report numerical analyses for the listed pharmacokinetic, efficacy, QTcB, microbiological, or palatability outcomes. Therefore, it cannot support a conclusion about the frequency of all TEAEs, the precision of an estimated effect, or a comparison with another regimen. Absence of a reported result in this record is not evidence that an outcome was absent.

More generally, the study’s non-randomized structure means that observed outcomes cannot be attributed to delamanid alone from these data. Participants received an optimized background regimen as well, and age groups received different formulations or doses. The registry record supports a description of study design and certain reported serious-event counts, but it does not establish comparative efficacy or comparative safety.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a clearly defined analysis population are important in clinical research. The primary endpoint counts participants with at least one TEAE, and the registry identifies a safety population based on receipt of any amount of investigational medicinal product. Those definitions specify what should be counted and who is intended to contribute, but interpretation still depends on the observed result, its denominator, and the method used to estimate uncertainty. The registry record does not report the primary numerical result or its analysis.

It also illustrates the limits of comparing age cohorts. The study includes four age groups with age-specific delamanid formulations or doses, but no randomized control group. The serious-event counts can describe what was recorded in each group; they cannot identify a causal explanation for differences between groups. This distinction is central when presenting outcomes from non-randomized studies: a visible difference is not automatically a treatment effect.

The study has several stated objectives and a list of secondary outcomes, while the registry record reports no analyses. This makes the separation between an outcome being planned or listed and an outcome having a reported estimate especially important. Statistical interpretation needs results, denominators, uncertainty measures, and details of analysis—not just outcome names.

Finally, a planning illustration based on an observed effect should not be mistaken for the original enrollment rationale or for observed power. Its assumptions describe a hypothetical two-arm calculation, whereas the actual study was organized into non-randomized age groups. Keeping design, planning, and results distinct prevents a planning calculation from being treated as evidence about what the study demonstrated.

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 registry record offers limited information for evaluating the primary outcome. Although the endpoint and timeframe are defined, its numerical result, analyzed denominator, and statistical analysis are not reported. No confidence interval or other measure of precision is reported. The record also does not provide the detailed results for the listed secondary outcomes, despite describing a broad set of safety, pharmacokinetic, and efficacy objectives.

The non-randomized, open-label design limits causal interpretation. All participants received delamanid with an optimized background regimen, and the four age groups differed by age and regimen details. The record therefore does not provide a randomized comparison that could separate the effect of delamanid from the background regimen or other differences among participants. The registry record does not report adjusted comparisons that might address measured differences between groups.

The serious-event term percentages are presented without denominator or age-group attribution in the information available. The record also does not provide event-level descriptions, timing, duration, or causal assessments for those terms. The reported death counts are descriptive, and the registry record does not report a comparative analysis of mortality.

Important statistical details are not reported in the registry record: a trial-specific sample-size justification, a statistical analysis plan, handling of missing data, multiplicity procedures, interim analyses, and outcome-specific analysis populations. The safety population definition is available, but that does not establish the denominator used for each result. These limitations constrain assessment of precision, bias, and the robustness of any outcome estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB) — NCT01859923.
• Registry record last updated 2020-11-23; status last verified 2020-10.
• Results first posted 2020-11-23.
• 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

This completed Phase 2 study enrolled 37 pediatric participants with multidrug-resistant tuberculosis and was non-randomized, open-label, and organized into parallel age groups. Participants received delamanid with an optimized background regimen; age groups differed in formulation and dose. Delamanid was administered up to Day 182, while the background regimen continued up to Day 365.

The primary endpoint was the number of participants with at least one TEAE from first dose through post-treatment follow-up, up to Day 365. The registry record does not report the numerical primary result or analyses of the listed outcomes. Descriptive serious adverse event counts are reported by age group, but they are not randomized comparisons. The record does not support a causal or comparative conclusion about safety or efficacy.