Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients (NCT01525628), a randomized phase 1 study. The primary outcome is Cmax of Faldaprevir (BI 201335).

2. Clinical Question

The trial’s broader aim was to assess how the antiviral combination affected exposure to other drugs and probe substrates, as well as how the study drugs affected one another. A pharmacokinetic interaction question concerns drug concentrations or exposure, rather than directly establishing a clinical benefit or harm. The registry also lists sustained virological response at twelve weeks as a secondary outcome, but numerical results for that outcome are not reported in the registry record.

3. Trial Design

This was a Phase 1, randomized, open-label, parallel-group trial. The registry reports enrollment of 72 and status as completed. The study began in 2012-04 and primary completion was in 2013-12. The sponsor was Boehringer Ingelheim. No publication details are reported in the registry record.

The registry describes five groups, labeled A through E, with distinct pharmacokinetic aims. Group A assessed the effect of BI 207127 on BI 201335, and effects of BI 201335 and the dual oral direct-acting antiviral combination on caffeine, tolbutamide, and midazolam. Group B assessed the effect of BI 201335 on BI 207127, and effects involving BI 207127 and metabolites and the dual antiviral combination on the same probe drugs. Group C assessed the effect of the dual oral antivirals on tenofovir. Group D assessed effects of BI 201335 and BI 207127 at 600 mg b.i.d. on the probe drugs. Group E assessed the effect of BI 201335 and BI 207127 on raltegravir.

The official title describes BI 207127 dosing at 600 mg t.i.d. or 600 mg b.i.d., BI 201335 at 120 mg q.d., and combination with ribavirin for 24 weeks. The registry does not report the randomization procedure, allocation ratio, group-specific enrollment targets, or whether any control condition was used. Open-label means masking was listed as none; the record does not describe further procedures to reduce measurement or analysis bias.

The primary endpoint was not planned for groups C, D, or E. This means the primary endpoint does not cover every group’s stated pharmacokinetic objective. The record lists 30 outcome measures and 78 analyses, but does not provide a complete description of how those analyses were organized or prioritized.

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: This was randomised (Groups A and B only), controlled, open-label, parallel-group (Groups A to E), multi-centre trial in treatment-naive patients and patients with prior treatment relapse or partial responders with Genotype 1 (GT1) chronic Hepatitis C infection.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.

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 treated set (TRT) included all patients who were dispensed trial medication and were documented to have taken at least one dose of trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Cmax of Faldaprevir (BI 201335), measured over PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66..

The primary endpoint was Cmax of faldaprevir (BI 201335), measured in ng/mL. Cmax is the highest observed plasma concentration of an analyte over the relevant sampling period. The endpoint description identifies it as the maximum concentration in plasma. In pharmacokinetic research, peak concentration can help characterize drug exposure and can be used when assessing whether another drug changes the concentration profile.

The registry reports the endpoint as a geometric mean with geometric coefficient of variation as the dispersion measure. In general, a geometric mean is suited to positive measurements that may be skewed, because it summarizes values on a multiplicative scale rather than treating equal absolute differences as the central feature. A geometric coefficient of variation describes relative spread on that scale. These summaries do not by themselves establish whether an interaction is clinically important.

Plasma samples were scheduled at 5 minutes before drug administration and at 1 hour, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, and 23:55h after the first drug administration on days 9, 17, and 66. The endpoint was defined for the pharmacokinetic set, which included treated patients with at least one observation for at least one primary pharmacokinetic endpoint and without important protocol violations relevant to pharmacokinetic evaluation. Numerical Cmax estimates and their dispersion are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described from the registry concern the trial structure, the primary endpoint’s summary scale, sampling, and the definition of the pharmacokinetic analysis population. Other analytic details, including the specific statistical model and the treatment of missing measurements, are not reported in the registry record.

What does a randomized parallel-group design mean?

In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences between groups, although it cannot ensure that every characteristic is balanced, especially when group sizes are limited. The registry identifies the study as randomized but does not report the allocation sequence, concealment procedures, or allocation ratio.

A parallel-group design assigns participants to a group and evaluates the assigned group’s treatment condition rather than having each participant move through every condition. The registry describes five groups with different pharmacokinetic objectives. It does not state that all five groups were intended to form one common comparison, and their objectives differ. The precise contrasts used for each analysis are not reported in the registry record.

Why use Cmax?

Cmax is the maximum concentration measured in plasma over a sampling period. In general, peak concentration is one aspect of drug exposure; it does not capture every feature of a concentration-time profile. Other pharmacokinetic measures may describe total exposure or the timing of concentration changes. The primary endpoint listed for this trial is Cmax, and the record does not provide its numerical estimate.

Sampling times matter because a peak could occur between scheduled observations. More frequent observations can help characterize the concentration curve, while the observed maximum is dependent on the sampling schedule and the measurements available. The registry lists samples before administration and at multiple times after the first administration on days 9, 17, and 66. It does not describe how the observed measurements were used to estimate the endpoint, or how unscheduled or missing samples were handled.

Why report a geometric mean?

The endpoint is summarized by a geometric mean, with geometric coefficient of variation as its dispersion measure. In general, concentration data are positive and may have a right-skewed distribution. A geometric summary can be useful when relative changes are more meaningful than absolute changes and when values vary multiplicatively. It is not the same as an arithmetic average, and the coefficient of variation is a relative measure of spread rather than a confidence interval.

A geometric coefficient of variation describes variability in relation to the geometric mean. It does not alone indicate the precision of the estimated mean. Precision is commonly conveyed with a confidence interval, which incorporates information about variability and the amount of data under a specified analysis. The confidence interval for the primary endpoint is not reported in the registry record.

What is the pharmacokinetic set?

The record defines the pharmacokinetic set as treated patients who had at least one observation for at least one primary pharmacokinetic endpoint and no important protocol violations relevant to pharmacokinetic evaluation. This is an analysis-population definition rather than a statement that every randomized participant contributed to every endpoint. The number included in the primary endpoint analysis is not reported in the registry record.

In general, an analysis population can affect interpretation because inclusion criteria determine which participants contribute to an estimate. Excluding observations or participants may be reasonable for a specified technical or protocol reason, but exclusions can also limit how well a result represents everyone randomized. The registry gives a definition but does not report the number excluded, reasons by group, or sensitivity analyses evaluating the effect of exclusions.

What can be inferred from the available statistical details?

The trial is described as a Phase 1 pharmacokinetic interaction study, and its endpoint specification gives the summary measure and dispersion measure. The registry does not report the model used to compare groups, transformations applied to concentrations, covariate adjustments, confidence interval procedure, significance threshold, or hypothesis-testing strategy. These methods should not be inferred from the use of a geometric mean alone.

In general, confidence intervals are useful because they express uncertainty around an estimate, while a p-value addresses compatibility of data with a specified null hypothesis under an analysis model. Neither is a substitute for understanding the effect estimate, the comparison, and the study’s precision. Since numerical estimates and inferential statistics for the primary endpoint are not reported in the registry record, those aspects cannot be assessed.

The registry includes 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. It describes effects to detect as stated fractions of the observed effect. Such illustrations are planning calculations, not observed power, and they do not establish the study’s original design justification. The trial’s own sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures and 78 analyses, alongside several pharmacokinetic objectives and a secondary virological outcome. With multiple outcomes, comparisons, or analyses, the chance of obtaining at least one apparently notable result can increase if each is assessed independently. In general, multiplicity procedures can control a chosen error rate or organize analyses into prespecified primary and secondary families. The registry record does not report whether multiplicity was addressed, which outcomes or contrasts were prioritized beyond the primary endpoint label, or whether any adjustment was used.

The primary endpoint was not planned for groups C, D, and E, while those groups have separate objectives involving tenofovir, probe drugs, or raltegravir. This makes it important to interpret each analysis against its own question rather than treating all findings as one overall comparison. The exact analysis hierarchy and any prespecified hypotheses are not reported in the registry record.

The endpoint’s pharmacokinetic-set definition requires an eligible observation and no important relevant protocol violation. The registry does not report how many participants contributed to each endpoint, the extent or reasons for missing data, whether missing measurements were imputed, or whether sensitivity analyses were conducted. In general, missingness can affect interpretation if the chance that a measurement is unavailable is related to the participant’s condition or concentration. Complete-case summaries may be less representative when missingness is systematic.

There is also no reported account of interim analyses or stopping rules. These details are not reported in the registry record and should not be assumed from the Phase 1 label or the trial’s completed status.

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: colitis ulcerative (7.1%), nausea (7.1%), complex partial seizures (6.2%), acute psychosis (6.2%), bipolar disorder (6.2%).

The registry reports serious adverse events by group. Group A had 0 affected participants among 16 at risk; Group B had 0 among 19; Group C had 1 among 16; Group D had 2 among 14; and Group E had 0 among 7. These are group-specific counts as listed in the registry, not estimates of a causal treatment effect. The groups had different stated pharmacokinetic objectives, so the counts should not be read as a simple randomized comparison of one treatment against a common control.

The registry also lists colitis ulcerative and nausea at 7.1%, and complex partial seizures, acute psychosis, bipolar disorder, and reactive psychosis at 6.2%, among the top serious adverse event terms. The record does not specify group assignment for these listed terms in the information described. Death counts are not reported in the registry record; a null entry is not evidence that no deaths occurred. Counts alone do not show event timing, duration, severity beyond the serious classification, or attribution to a study drug. The record does not provide a comparative safety analysis or enough detail to determine whether an event was caused by treatment.

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

This trial is relevant as a Phase 1 investigation of pharmacokinetic interactions involving BI 201335, BI 207127, ribavirin, and several other drugs or probe substrates in people with chronic genotype 1 hepatitis C infection. Its primary endpoint, Cmax of faldaprevir, addresses peak plasma concentration. The distinct group objectives show that the study considered more than one drug-interaction question.

The registry record does not report numerical results for the primary endpoint. It therefore does not establish the size, direction, or precision of the primary pharmacokinetic effect. The same limitation applies to the listed secondary outcome, SVR12: its numerical results are not reported in the registry record. The design description and endpoint definitions cannot substitute for outcome estimates.

In general, a pharmacokinetic change describes a difference in drug concentration or exposure, not by itself a clinical benefit or harm. Its interpretation depends on the size and precision of the estimate, the particular drug pair, the timing and dosing conditions, and relevant clinical context. Those numerical and contextual details are not reported sufficiently for conclusions about the implications of any interaction.

The serious adverse event counts document the registry’s group-level entries, but they do not establish whether an event was caused by a study drug or whether risks differed between treatments. The group objectives and sizes vary, and the registry record does not report a formal comparative safety analysis. Nor does the record report death counts.

Accordingly, the information supports describing what the study was designed to examine and how its primary endpoint was defined. It does not support a conclusion that the treatments were effective or ineffective, that an interaction was present or absent, or that a particular treatment was safe or unsafe. Those claims would require outcome estimates, uncertainty measures, and fuller analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

The trial illustrates why pharmacokinetic studies may need several focused questions rather than a single broad treatment comparison. BI 201335 and BI 207127 were assessed in relation to each other, while the regimen was also examined with probe substrates and with tenofovir or raltegravir. Each drug combination can have a distinct concentration profile, so results for one objective would not automatically generalize to another.

It also illustrates the importance of distinguishing endpoint definition from endpoint result. The registry specifies Cmax, its units, its geometric summary, dispersion measure, sampling times, and analysis-population criteria. These details clarify what was intended to be measured. But without a numerical estimate and an uncertainty measure, the extent and precision of the observed effect cannot be evaluated.

Multiple outcomes and analyses raise questions about which comparisons were planned as primary and how multiplicity was addressed. The registry lists many outcomes and analyses but does not report an adjustment strategy or a complete analysis hierarchy. This makes it important not to interpret isolated findings without knowing how they fit into the full set of planned analyses.

Finally, the record distinguishes pharmacokinetic questions from the secondary virological outcome and safety reporting. Concentration measures, virological response, and adverse events answer different questions and require different interpretations. A clear statistical account would connect each estimate to its intended comparison, analysis population, and uncertainty. The available record describes important design features but does not report the numerical results needed for that assessment.

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.

A central limitation for interpreting this trial record is that numerical results for the primary endpoint are not reported in the registry record. Without an estimate and a measure of precision, the direction, magnitude, and uncertainty of the Cmax finding cannot be assessed. Numerical results for SVR12 are also not reported in the registry record.

The group descriptions cover different pharmacokinetic objectives rather than one uniform treatment comparison. The precise contrasts, group-level result estimates, and analysis populations for each endpoint are not reported in the registry record. Although the primary endpoint population is defined, the number analyzed and any exclusions are not reported.

The statistical analysis plan is not described in sufficient detail to identify the model, adjustments, confidence-interval method, missing-data approach, or multiplicity strategy. The registry record also does not report the trial’s own sample-size justification, interim analyses, or stopping rules. Those omissions limit assessment of the planning and inferential framework.

The study was open-label, with masking listed as none. The registry does not describe whether laboratory personnel or analysts were masked, or whether procedures were used to limit bias in sample processing and endpoint evaluation. It also does not report group-level baseline characteristics in the information described.

Safety entries provide serious adverse event counts by group and a list of top serious terms, but not an attribution analysis or a comparative safety estimate. Death counts are not reported in the registry record. The record’s completed status alone does not resolve these reporting limitations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients — NCT01525628.
• Registry record last updated 2016-06-10; status last verified 2016-05.
• Results first posted 2016-06-10.
• 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.

18. Record Summary

NCT01525628 was a completed, randomized, open-label, parallel-group Phase 1 trial sponsored by Boehringer Ingelheim. The registry reports enrollment of 72 and describes five groups with pharmacokinetic objectives involving BI 201335, BI 207127, probe drugs, tenofovir, and raltegravir in people with chronic genotype 1 hepatitis C infection.

The primary endpoint was Cmax of faldaprevir (BI 201335), summarized as a geometric mean with geometric coefficient of variation. The pharmacokinetic sampling schedule and analysis-set definition are reported. The registry also lists SVR12 as a secondary outcome and reports group-level serious adverse event counts.

Numerical primary-endpoint and SVR12 results, detailed statistical methods, multiplicity handling, and missing-data procedures are not reported in the registry record. Accordingly, the record describes the study’s aims and methods more fully than its numerical findings.