Safety, Tolerability and Pharmacokinetics of Different Multiple Doses of BI 207127 BID and Multiple Doses of BI 207127 Combined With Faldaprevir in Healthy Male and Female Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Pharmacokinetics of Different Multiple Doses of BI 207127 BID and Multiple Doses of BI 207127 Combined With Faldaprevir in Healthy Male and Female Subjects (NCT01737996), a non-randomized phase 1 study. The primary outcome is Number of Healthy Subjects With AEs (Multiple Rising Dose Part).

2. Clinical Question

This is a descriptive early-phase study question rather than a confirmatory comparison of treatment effects. The registry record identifies an open-label study, so treatment assignment was not masked. The regimens also differ in whether faldaprevir was included, and the arms were not randomized. Consequently, differences in posted event counts should be read as descriptions of the groups in this study, not as unbiased estimates of what would happen if otherwise comparable subjects received one regimen rather than another.

3. Trial Design

The record identifies this as a Phase 1, open-label, non-randomized study with a single-group model. Its official title describes two parts: BI 207127 administered orally for 9 days in Part 1, and BI 207127 combined with faldaprevir administered orally for 16 days in Part 2. The stated purpose was to assess safety, tolerability, and pharmacokinetics in healthy male and female subjects.

The listed regimens are 400 mg deleobuvir, 600 mg deleobuvir, and 600 mg deleobuvir with 120 mg faldaprevir. The arm description says that subjects received low-dose or high-dose BI 207127 for the first 9 days, followed by high-dose BI 207127 with faldaprevir. The registry record lists 8 subjects at risk in each deleobuvir-alone group and 16 in the combination group for the reported adverse-event summaries.

Because the study was non-randomized and open-label, the groups should not be treated as exchangeable arms in a controlled trial. The record explicitly cautions that the arms are not a like-for-like control comparison. It does not report how subjects were assigned to regimens or whether the same subjects contributed observations across parts; those details are not reported in the registry record.

The primary endpoint concerns adverse events in the Multiple Rising Dose Part, with a stated observation window from first administration on Day 1 until the end-of-trial examination, 15 to 21 days after first administration. Enrollment was 32, and the study status is completed. The record does not report a randomized allocation sequence, masking, or a separate placebo or active control arm. It also does not report a protocol-level statistical analysis plan or a sample-size justification.

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: The 600mg dose cohort was to be started at least 6 days after the 400mg dose cohort was completed and the combined treatment cohort (600mg Deleobuvir + 120mg Faldaprevir) was started after the evaluation of key safety and tolerability data of the individual treatments.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated Set. The treated set included all subjects who were documented to have taken at least 1 dose of study medication.

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 study comprised 2 trial parts: a multiple rising dose part (Part 1) followed by a combined treatment part (Part 2). The multiple rising dose part was performed in an open-label, non-randomised, non-placebocontrolled manner with 2 dose groups. The combined treatment part was conducted open-label in 1 treatment group.

6. Primary Endpoint

The registry lists the primary outcome as Number of Healthy Subjects With AEs (Multiple Rising Dose Part), measured over From first drug administration (Day 1) until end of trial examination (15 to 21 days after first administration).

The primary endpoint is the number of healthy subjects with any adverse event during the on-treatment period in the Multiple Rising Dose Part. The registry defines the population as the Treated Set: subjects documented to have taken at least 1 dose of study medication. The observation window runs from first drug administration on Day 1 until the end-of-trial examination, stated as 15 to 21 days after first administration.

This endpoint is a count of participants with an event, rather than a measure of how many events each person experienced or how severe an event was. It is used in safety assessment because it records whether an adverse event was observed during the specified exposure and follow-up period. A count alone does not describe event timing, duration, seriousness, relatedness to study medication, or the number of recurrent events; those details are not reported for this primary measure in the registry record.

The listed adverse-event results distinguish serious events from other adverse events. The record gives the number of subjects affected in each group, but it does not provide a primary-endpoint inferential analysis. In particular, it does not report a confidence interval or a statistical test comparing groups. The listed secondary outcomes focus on pharmacokinetic measures, including AUC and Cmax for deleobuvir and related compounds. Those outcomes address exposure profiles and are separate from the primary safety count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available results are counts of subjects with adverse events, separated by regimen. The primary endpoint is a binary participant-level outcome: a subject either had at least one adverse event during the specified period or did not. The posted count records how many subjects met that definition. It does not count every event separately, so repeated events in one subject do not necessarily increase the participant count.

What does a count describe?

In general, a count is most informative when read together with the group to which it refers and the number of people assessed. Here, the registry reports both affected-subject counts and numbers at risk for each regimen. The counts describe the observations in these study groups. They do not by themselves show whether a difference is due to the regimen, chance variation, or other differences between groups. Since allocation was non-randomized, causal interpretation of between-group differences is especially limited.

The primary endpoint’s population is the Treated Set, defined as subjects documented to have taken at least 1 dose of study medication. This definition focuses the safety count on people who were exposed to study medication. The registry record does not state how missing event information was handled, whether all treated subjects completed follow-up, or whether a separate population was used for the other outcomes. Those details are not reported in the registry record.

What would uncertainty estimates add?

In general, a confidence interval describes statistical uncertainty around an estimate under the model and assumptions used to calculate it. For a participant-level event outcome, an interval around a group estimate could show how imprecisely the event frequency is estimated. An interval for a contrast between groups could also show uncertainty about the difference being assessed. The registry record does not report confidence intervals or inferential comparisons for the adverse-event counts, so the posted summaries do not quantify that uncertainty.

In general, a p-value evaluates how compatible data are with a specified statistical null hypothesis under stated assumptions. It is not a measure of the size or clinical importance of an effect. No p-values or test results are reported for the primary endpoint, and the registry lists 0 analyses. It is therefore not appropriate to infer statistical significance or absence of a difference from the counts alone.

Why does allocation matter?

In general, random allocation can help balance measured and unmeasured characteristics between groups, while non-random allocation can leave groups systematically different. This record identifies allocation as non-randomized and warns that the arms are not a like-for-like control comparison. The groups also correspond to different regimens, including a combination regimen. Consequently, any observed contrast could reflect differences beyond the named drug regimen. The record does not report an adjusted analysis that might address measured differences.

The study is open-label, meaning masking is listed as none. In general, lack of masking can affect the reporting, recognition, or assessment of outcomes, although the magnitude and direction depend on the outcome and study procedures. The registry record does not describe event adjudication or provide information that would establish whether outcome assessment was independent of treatment knowledge.

How should the pharmacokinetic outcomes be understood?

The listed secondary outcomes include AUC and Cmax for deleobuvir and related compounds, with measures for single intervals and steady state. In general, AUC summarizes drug exposure over a specified interval, while Cmax is the highest measured concentration over a specified sampling period. These are pharmacokinetic measures, not clinical event counts. Their interpretation depends on sampling schedules, analytic methods, and the specified time interval; those details and the numeric results are not reported in the registry record.

The registry lists 23 outcome measures and multiple secondary pharmacokinetic outcomes. In general, evaluating many outcomes can raise a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. The registry record does not report a multiplicity strategy, hypothesis hierarchy, or adjustment. Nor does it report enough analysis detail to determine how outcome-specific estimates were calculated.

A sample-size calculation is a planning exercise, not a statement about the strength of evidence ultimately observed. In general, planning estimates depend on assumptions about the effect to detect, variability, significance level, allocation, and statistical model. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on an observed effect should not be read as observed power or as evidence that the study could reliably detect a clinically meaningful difference.

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("400 mg Deleobuvir", "600 mg Deleobuvir")
n      <- c(8, 8)
events <- c(6, 5)
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  400 mg Deleobuvir  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  600 mg Deleobuvir  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 23 outcome measures, including secondary pharmacokinetic outcomes for deleobuvir and related compounds. It reports 0 analyses. A statistical plan for managing multiple outcomes or multiple comparisons is not reported in the registry record. Without that information, it is not possible to determine whether outcomes were prioritized in advance, whether any adjustment for multiplicity was planned, or how formal testing would have been interpreted.

Missing-data methods are also not reported in the registry record. The primary endpoint specifies the Treated Set, consisting of subjects documented to have taken at least 1 dose of study medication, but the record does not describe how missing adverse-event information, incomplete follow-up, or withdrawals were handled. It does not report whether all subjects in that set contributed complete endpoint data.

The registry identifies a primary endpoint and its observation period, but does not report a complete statistical analysis plan, analysis models, covariate adjustments, or rules for handling outcomes that could not be assessed. Such information matters because choices about analysis populations and missing observations can affect the results and their interpretation. No assumptions about those procedures should be inferred from the posted counts.

The available adverse-event summaries are descriptive. They do not include inferential comparisons, confidence intervals, or a stated approach to multiplicity. The listed Treated Set definition clarifies who is intended to contribute to the primary safety outcome, but it does not resolve the unreported analysis and missing-data details.

12. 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 non-serious adverse event terms

The registry reports 0 serious adverse events in each of the three listed groups. It reports 8 subjects at risk in each deleobuvir-alone group and 16 in the 600 mg deleobuvir plus 120 mg faldaprevir group. These are posted group-level counts; they should not be interpreted as proof that serious events cannot occur with any regimen.

The registry separately reports other adverse events affecting 6 subjects in the 400 mg deleobuvir group, 5 in the 600 mg deleobuvir group, and 9 in the combination group. These figures describe affected subjects, rather than the total number of individual events. The record does not provide further detail about event type, severity, timing, relatedness, or recurrence.

Deaths are listed without numeric values. This means a death count is not reported in the registry record; it should not be treated as a reported zero. Because the study was non-randomized and the groups are not like-for-like controls, the adverse-event counts do not establish comparative risks between regimens.

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

The record establishes that the study evaluated safety, tolerability, and pharmacokinetics of multiple-dose BI 207127, including a regimen combined with faldaprevir, in healthy male and female subjects. It identifies the primary safety endpoint as the count of treated subjects with any adverse event during the on-treatment period. The posted results describe affected-subject counts by regimen and report no serious adverse events in the listed groups.

These results do not establish that the regimens have equivalent safety, that a serious event cannot occur, or that one regimen is safer than another. The study was non-randomized and open-label, and the registry cautions that the arms are not like-for-like controls. The group counts are therefore descriptive rather than a controlled estimate of a causal difference.

The registry record does not report a comparative test, confidence interval, or analysis model for the adverse-event results. It also does not report numeric pharmacokinetic findings in the information available for this interpretation. Thus, no conclusion about statistical significance, precision of a between-group effect, or pharmacokinetic exposure differences can be drawn from these registry entries.

The findings apply to the study population and observation window described in the record. They concern healthy subjects who met the Treated Set definition, not a broader population. The record does not establish how these observations translate to other populations or settings. The results are useful as a description of what the registry reports for this early-phase study, but their scope is limited by the design and the absence of reported inferential analyses.

14. Why This Trial Matters Statistically

This study illustrates the distinction between descriptive safety summaries and comparative evidence. Counts of subjects with adverse events are useful for showing what was recorded in each regimen group. But when assignment is non-randomized and the record explicitly says the arms are not like-for-like controls, a difference in counts cannot be attributed to the regimen alone.

It also shows why denominators and outcome definitions matter. The primary endpoint is defined for a treated population and a stated observation period. The adverse-event summaries separately identify serious and other events, while the primary endpoint concerns any adverse event. Clear definitions help readers understand what a count represents, but they do not replace information about event characteristics, missing observations, or the analysis method.

For biostatistical interpretation, the absence of reported inferential analyses is consequential. Without confidence intervals or a formal comparison, the precision of any between-group contrast is unknown. A zero serious-event count in a group is an observed summary, not proof of zero underlying risk. Likewise, the listed pharmacokinetic outcomes indicate what was intended to be assessed, but do not supply numeric findings.

The registry record is therefore informative about study structure, endpoint definitions, and posted safety counts, while leaving important statistical details unreported. It provides a focused example of how design, allocation, endpoint construction, and incomplete analysis reporting constrain what can be concluded from trial results.

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 interpretation is the non-randomized, open-label design. The registry record itself cautions that the arms are not a like-for-like control comparison. Any differences in adverse-event counts may reflect differences between groups or study procedures, and the record does not report adjusted analyses to address these possibilities.

The reported group sizes are limited, and the serious-event counts are zero in each group. Such summaries cannot precisely characterize uncommon events. No confidence intervals or formal comparisons are reported, so uncertainty around the group-level event estimates and any contrast is not quantified.

The record gives affected-subject counts for other adverse events but does not report event descriptions, severity distributions, relatedness assessments, timing, duration, or recurrent-event counts. Death counts are not numerically reported. Handling of missing event information and incomplete follow-up is not reported in the registry record.

The primary endpoint is specified for the Treated Set, but the record does not describe additional analysis populations or provide a full statistical analysis plan. Multiplicity procedures, sample-size justification, interim analyses, and model specifications are not reported in the registry record. The pharmacokinetic outcomes are listed, but numeric results and analytic details are not available in the record details used for this interpretation. These limitations restrict interpretation to the design description and posted adverse-event counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability and Pharmacokinetics of Different Multiple Doses of BI 207127 BID and Multiple Doses of BI 207127 Combined With Faldaprevir in Healthy Male and Female Subjects — NCT01737996.
• Registry record last updated 2016-04-08; status last verified 2016-03.
• Results first posted 2016-04-08.
• 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 1 study evaluated multiple doses of BI 207127 alone and in combination with faldaprevir in healthy male and female subjects. It was open-label and non-randomized. The stated study objective was to assess safety, tolerability, and pharmacokinetics.

The primary endpoint counted treated subjects with any adverse event during the on-treatment period. The posted results report no serious adverse events in the three listed regimen groups and report other adverse events affecting 6, 5, and 9 subjects, respectively. The registry record warns that the groups are not like-for-like controls.

No inferential analyses are reported. The record does not report confidence intervals, a formal comparison, missing-data procedures, or a multiplicity strategy. The adverse-event results should therefore be read as descriptive counts, not as evidence of comparative treatment effects.