To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB. (NCT00910871), a na phase 2 study. The primary outcome is The Median Time to Sputum Culture Conversion.

2. Clinical Question

The clinical question was whether adding TMC207 to an individualized MDR-TB drug regimen could be evaluated for safety, tolerability and effectiveness in this study population. Because participants were not assigned to a separate control group, the design does not provide a concurrent between-group comparison. Any interpretation of culture conversion therefore needs to stay within the limits of a single-group study and the endpoint definition recorded for the trial.

3. Trial Design

This was a Phase II, open-label, single-group trial sponsored by Janssen Infectious Diseases BVBA. The record lists 241 participants enrolled, no masking, and allocation as NA. The study status is completed. Its recorded start was 2009-09 and its primary completion was 2011-03.

Participants received TMC207 as part of an individualized background regimen of antibacterial drugs for MDR-TB. The recorded TMC207 regimen was 400mg once daily for 2 weeks, then 200mg three times a week for 22 weeks. No separate background-regimen-only arm is listed. Consequently, the design does not support a direct randomized comparison between TMC207 plus background treatment and background treatment alone.

The registry describes the primary endpoint as median time to sputum culture conversion up to Week 24. The efficacy analysis population was defined as participants who received at least 1 dose of TMC207, excluding participants with drug-susceptible tuberculosis or those not evaluable for efficacy. Although the registry says this was the modified intent-to-treat population used for all efficacy analyses, its size is not reported. The enrolled total should not be treated as the efficacy denominator.

The record lists a secondary outcome, the percentage of participants with sputum culture conversion. It also records 2 outcome measures, but does not provide the numerical primary endpoint result in the information available for interpretation. Detailed allocation procedures, a protocol-level statistical plan, sample-size justification and interim-analysis details are not reported in the registry record. The study's open-label, single-group structure is central to interpreting both the endpoint and the safety information: the reported observations do not establish what would have happened under a separate comparator regimen.

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 241 participants were enrolled in the study; 8 participants were withdrawn from the study before study drug administration and 233 started treatment with study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (mITT) population used for all efficacy analyses included all randomized participants who received at least 1 dose of TMC207 excluding participants with drug-susceptible tuberculosis (DS-TB) or participants that were not evaluable for efficacy.

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: Intent-to-treat (ITT) population included all participants who had at least 1 dose of TMC207, regardless of their compliance with the protocol.

6. Primary Endpoint

The registry lists the primary outcome as The Median Time to Sputum Culture Conversion, measured over Up to Week 24.

The primary endpoint was the median time to sputum culture conversion, measured in days through Week 24. Conversion was defined as 2 consecutive sputum cultures negative for MDR-TB, with the samples taken at least 25 days apart. The registry specifies that the endpoint was based on Mycobacteria Growth Indicator Tube (MGIT) results.

Time to conversion captures both whether the defined event occurred during follow-up and how long it took to occur. A median is a measure of the midpoint of the observed time-to-event distribution, rather than an average. This can be useful when event times are not symmetrically distributed or when the focus is on the time until a clinically relevant laboratory milestone. These are general properties of time-to-event outcomes, not statements about the distribution in this trial.

The endpoint definition also specifies how discontinuation was treated: participants who discontinued during the 24-week period were considered non-responders. This rule matters because the endpoint is not merely a culture result at one visit; it depends on meeting the specified sequence and spacing of negative cultures within the assessment period.

The registry record does not report the median time or its 95% confidence interval. Thus, the endpoint's definition and analysis population can be described, but the reported magnitude and precision of the primary result cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median time to event describe?

In general, a time-to-event outcome records the time from a defined starting point until a specified event occurs. For this trial, the event was sputum culture conversion as defined by the registry, and the reported unit was days. The median is the point in the time distribution at which half of the observations lie on either side, subject to how the analysis handles participants whose event time is not observed. It is not the same as the mean, and it does not describe every participant's individual time to conversion.

The registry names a median and a 95% confidence interval as the intended primary summary, but does not report either numerical value. Therefore, no statement about the observed median, the width of its interval, or the degree of precision is possible. General interpretation of a confidence interval is that it expresses uncertainty around an estimate under the assumptions of the method used. It is not a range that guarantees where every participant's event time lies.

Why does the event definition matter?

The endpoint required 2 consecutive negative sputum cultures for MDR-TB, taken at least 25 days apart, and was assessed up to Week 24 using MGIT. A single negative culture would not meet that definition. The required sequence and interval make the endpoint a rule-based event rather than simply a result from one culture collection. The registry also specifies that participants who discontinued during the 24-week period were considered non-responders. That approach determines how discontinuation contributes to the endpoint classification; it does not, by itself, explain why participants discontinued or how many did so.

In general, time-to-event analyses may need to account for participants whose event is not observed during follow-up. Some methods use censoring, while a trial may define other outcome rules for particular circumstances. The specific statistical method used to estimate the median is not reported in the registry record. It would be inappropriate to assume a Kaplan-Meier estimator, a particular censoring convention, or any other procedure not stated there.

What can be inferred from a single-group design?

The study is recorded as single-group, open-label, with allocation listed as NA. In general, an uncontrolled study can describe outcomes observed among participants receiving a regimen, but it does not supply a concurrent treatment group for estimating a between-group contrast. For this trial, TMC207 was given alongside an individualized background regimen. The observed endpoint would therefore pertain to the combined treatment context; the design does not isolate the contribution of one component from the other.

Open-label means masking was recorded as none. In general, lack of masking can influence aspects of care, assessment or reporting, depending on the outcome and study procedures. Culture conversion is laboratory-defined, but the registry record does not report enough operational detail to assess how any open-label features may have affected specimen collection, follow-up or decisions about discontinuation.

How should the analysis population be read?

The registry defines the modified intent-to-treat efficacy population as participants who received at least 1 dose of TMC207, excluding those with drug-susceptible tuberculosis or those not evaluable for efficacy. It says that this population was used for all efficacy analyses. The count in that population is not reported. The 241 enrolled participants and the 233 participants listed as at risk for safety are not interchangeable with this efficacy denominator.

In general, an analysis population definition determines which participants contribute to a particular estimate. Exclusions can affect how broadly that estimate applies, especially if the excluded participants differ from those included. The registry does not report the number excluded for each reason or the characteristics of excluded participants, so the impact of the exclusions cannot be assessed.

What do the safety counts and planning illustrations mean?

For safety, the record lists 233 participants at risk, 47 with serious adverse events, and 179 with other adverse events. These figures describe the recorded group; they do not establish causality. The selected serious-event terms are accompanied by percentages, but the record does not provide event-level timing, duration, attribution or a comparison group in the information. In general, adverse-event summaries describe events observed during a study, while causal interpretation requires more than a count alone.

The registry's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. Such illustrations are planning calculations, not observed power and not evidence that the original study was designed as a two-arm trial. The trial itself is listed as single-group, and numerical planning results are not reported in the registry record information available for this interpretation. The protocol's sample-size justification is not reported.

The number of analyses is recorded as 0. The statistical method used for the primary endpoint, any model adjustments, handling of multiple outcomes, and any interim analyses are not reported in the registry record. General statistical explanations do not substitute for those missing trial-specific methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the median time to sputum culture conversion as the primary outcome and the percentage of participants with sputum culture conversion as a secondary outcome. It records 2 outcome measures and 0 analyses. Numerical results for these outcomes are not reported in the registry information available for interpretation.

Multiplicity is the statistical issue that arises when several outcomes, time points or comparisons are assessed. In general, examining multiple results can increase the chance of at least one apparently notable finding by chance. A prespecified strategy may address that issue, but the registry record does not report whether any multiplicity adjustment was planned or applied. It also does not report the full analysis plan, a hierarchy among outcomes, or whether other analyses were conducted outside the listed record.

The efficacy analysis population is described as participants who received at least 1 dose of TMC207, excluding participants with drug-susceptible tuberculosis or those not evaluable for efficacy. The count in that population and the numbers excluded for each reason are not reported. Participants who discontinued during the 24-week period were considered non-responders for the primary endpoint. The record does not give the number of discontinuations or further details about missing culture assessments.

Thus, the stated non-responder rule is a specific endpoint-handling decision, but it does not provide a complete account of missing-data procedures. Other rules for unavailable cultures, missed visits or incomplete follow-up are not reported in the registry record. Interim analyses, stopping criteria and the protocol's statistical plan are also not reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: tuberculosis (2.6%), pneumothorax (2.1%), haemoptysis (1.7%), pneumonia (1.3%), cardiac failure congestive (0.9%).

The safety record lists 233 participants at risk in the TMC207 group. It reports 47 participants with serious adverse events and 179 with other adverse events. The record does not define the “other” category further in the information available for interpretation, so it should not be assumed to mean a particular severity class or to be mutually exclusive of serious events.

The listed serious adverse-event terms and percentages are tuberculosis, 2.6%; pneumothorax, 2.1%; haemoptysis, 1.7%; pneumonia, 1.3%; cardiac failure congestive, 0.9%; and treatment failure, 0.9%. These figures describe events recorded in the trial; without a comparator group, they do not establish whether the regimen changed the risk of an event. Nor do the percentages alone show event timing, duration, severity beyond the serious-event classification, or whether investigators considered an event related to treatment.

The record gives no numerical death count; deaths are not reported in the registry record. The serious-event counts and selected terms are safety descriptions, not a causal analysis. Interpretation is further limited by the open-label, single-group design and the absence of a concurrent control arm.

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

The record identifies a Phase II, open-label study of TMC207 given with an individualized MDR-TB background regimen and defines a primary culture-conversion endpoint. It also provides selected adverse-event counts and terms. These details describe the study question, treatment context, endpoint rules and some recorded safety observations.

The record does not report the primary median time to sputum culture conversion or its 95% confidence interval. As a result, the size and precision of the primary endpoint estimate cannot be assessed. The numerical result for the listed secondary outcome is also not reported in the registry record information available for interpretation. No result should be inferred from the enrollment count, regimen description or adverse-event percentages.

The design places an important boundary on conclusions. Participants received TMC207 together with an individualized background regimen, and the study is listed as single-group with no masking. There is no separate control arm for a like-for-like comparison. Consequently, the observed study experience cannot isolate the contribution of TMC207 from the background regimen or other influences, and it does not provide a randomized estimate of a treatment difference.

The culture-conversion definition is specific: 2 consecutive negative cultures at least 25 days apart, assessed up to Week 24, with discontinuers treated as non-responders. Those rules clarify what counted as the endpoint, but the record does not report the number of participants who converted, the time distribution, or how many discontinued. The efficacy population's size is also not reported.

The safety counts are descriptive observations among participants at risk. In the absence of a comparator and further event-level information, they should not be read as proof that treatment caused or prevented any particular event. Overall, the registry record supports a description of the study's design and endpoint definitions, but its available result detail does not permit a full assessment of efficacy magnitude, uncertainty or comparative safety.

13. Why This Trial Matters Statistically

This trial illustrates why a statistical result needs to be read together with its design and endpoint definition. The primary outcome is a time-to-event measure, but the event was defined through a sequence of culture results with a minimum interval between samples. That definition affects which participants meet the conversion criterion and distinguishes the endpoint from a single negative culture.

The record also shows how analysis populations matter. The enrolled total is 241, the safety group lists 233 at risk, and the efficacy population is defined using additional eligibility and evaluability criteria. Because the efficacy population count is not reported, those figures should not be treated as equivalent denominators. Clear denominator reporting is necessary to understand who contributes to each result.

The single-group, open-label structure provides a useful statistical lesson about descriptive versus comparative evidence. Outcomes observed under a combined regimen can characterize that study experience, but without a separate control group they cannot quantify a between-regimen difference. This remains true even when an endpoint is objectively defined; the design determines what kinds of comparisons the data can support.

Finally, the registry record names a median and a 95% confidence interval but does not report their numerical values. Statistical interpretation requires both an estimate and information about its uncertainty. A defined endpoint or a list of safety events cannot substitute for the missing primary result. The record therefore demonstrates the importance of complete result reporting alongside transparent endpoint and population definitions.

14. 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 primary endpoint estimate and its 95% confidence interval are not reported in the registry record. The numerical result for the secondary percentage with sputum culture conversion is also not reported in the information available for interpretation. This prevents assessment of the observed endpoint magnitude and its precision.

The study is listed as a single-group, open-label trial, with allocation recorded as NA. No separate control group is listed. This limits causal interpretation and prevents a direct comparison with another treatment regimen. Because TMC207 was administered with an individualized background regimen, the record cannot isolate the contribution of TMC207 from that of the accompanying drugs.

The efficacy population definition is available, but its size and the number excluded for drug-susceptible tuberculosis or lack of efficacy evaluability are not reported. The 241 enrolled participants and the 233 listed as at risk for safety should not be assumed to be the efficacy denominator. The number of discontinuations and the number of missing or unevaluable culture assessments are also not reported.

Participants who discontinued during the 24-week period were considered non-responders. The registry does not describe other missing-data procedures, the method used to estimate the median, any model adjustments, or the handling of incomplete culture follow-up. It does not report a multiplicity strategy, interim analyses, stopping criteria, or a protocol-level statistical plan. The protocol's sample-size justification is not reported; the planning illustration is not a description of the trial's own design.

Safety information is limited to group counts and selected serious-event terms and percentages. Deaths are not reported in the registry record. Event timing, attribution and comparative safety results are not available in the record information used for this interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB. — NCT00910871.
• Registry record last updated 2015-04-24; status last verified 2015-04.
• Results first posted 2013-05-16.
• 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.

18. Record Summary

The registry record describes NCT00910871 as a completed Phase II, open-label, single-group trial sponsored by Janssen Infectious Diseases BVBA. It lists 241 participants enrolled and evaluates TMC207 in addition to an individualized background regimen for sputum smear-positive pulmonary MDR-TB.

The primary outcome was median time to sputum culture conversion through Week 24, defined by 2 consecutive negative cultures at least 25 days apart. Participants who discontinued during the 24-week period were considered non-responders. The efficacy population's size, primary median and 95% confidence interval are not reported in the registry record information available for interpretation.

The safety group lists 233 participants at risk, 47 with serious adverse events and 179 with other adverse events. The record lists selected serious-event terms and percentages; deaths are not reported. No separate control arm is listed, so the study does not provide a direct randomized comparison.