A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants (NCT03928327), a non-randomized phase 1 study. The primary outcome is Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914.

2. Clinical Question

3. Trial Design

This was a Phase 1 study of oral TAK-788 in healthy adult participants. The registry record lists a sequential model, non-randomized allocation and no masking. Enrollment was 24, and the study status is completed. The listed start date is 2019-05-02 and the primary completion date is 2019-08-16.

The study had two parts. In Part 1, Treatment Sequence AB began with Treatment A: TAK-788 20 mg at Hour 0 on Day 1 after an overnight fast. Treatment B involved itraconazole 200 mg orally once daily on Days 1 to Day 14, with a single oral dose of TAK-788 20 mg coadministered on Day 5. The primary endpoint compares B with A.

In Part 2, Treatment Sequence CD began with Treatment C: TAK-788 160 mg orally at Hour 0 on Day 1 following an overnight fast. Treatment D involved rifampin 600 mg orally once daily on Days 1 to 13, with TAK-788 160 mg coadministered on Day 7. The registry record does not provide complete details of the treatment descriptions, including the full washout information.

The sequential, non-randomized structure is important when interpreting the comparisons. This is not a randomized comparison between independent groups. Treatment order, the distinct parts and the specific coadministered drug all matter when describing what the study can establish. The registry record does not report additional design details such as a formal 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: Healthy participants were enrolled in this 2-period study to receive: TAK-788 20 mg (Treatment A) along with itraconazole 200 mg (Treatment B) and TAK-788 160 mg (Treatment C) with rifampin 600 mg (Treatment D) in sequential manner to evaluate drug-drug interaction.

Period 1

Washout Period

Period 2

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Set included participants who complied sufficiently with the protocol and display an evaluable PK profile.

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 Set included participants who received at least one dose of a study drug.

6. Primary Endpoint

The registry lists the primary outcome as Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914, measured over Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose.

The primary endpoint is the combined molar exposure Cmax for TAK-788 and the metabolites AP32960 and AP32914 in Part 1, comparing Treatment B with Treatment A. Cmax is the maximum observed plasma concentration after dosing. It describes the peak concentration observed during the specified sampling period; it does not describe the full concentration-time profile or total exposure by itself.

The registry record states that the combined molar value was calculated by summing the molar Cmax values for TAK-788 and its metabolites, using molecular-weight conversion, and reported in nM. Combining analytes in molar units is intended to represent their concentrations on a common basis rather than simply adding concentrations expressed in different mass units. The record’s endpoint description also refers once to AP3914, while elsewhere it names AP32914; this inconsistency is not resolved in the registry record.

Peak concentration is useful in pharmacokinetic studies because it offers a direct measure of the highest observed plasma level under each treatment condition. It can be considered alongside other pharmacokinetic measures, but the registry record does not identify a clinical threshold or explain how this endpoint relates to clinical outcomes. The estimate, its variability and any uncertainty interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the endpoint definition and the PK population, but gives limited information about the statistical analysis. The concepts below are general statistical context for interpreting the kind of measure named in the record; they are not claims about methods used in this study unless explicitly identified as registry entries.

What does Cmax represent?

Cmax is the highest measured plasma concentration during the scheduled observation period. In this study, the timeframe is Day 1 pre-dose and multiple post-dose time points up to 240 hours. It is an observed maximum, so its value can depend on when samples are collected as well as on the concentration-time profile. Cmax is different from an area-under-the-curve measure, which summarizes concentration over time. The registry record identifies Cmax as the primary endpoint but does not report the actual sampling times beyond the stated timeframe or the endpoint values.

Why use a combined molar measure?

The endpoint combines the molar Cmax values for TAK-788 and its metabolites, expressing the result in nM. In general, molar concentrations put different analytes on a shared molecule-count basis, making a combined concentration interpretable as a sum of molar contributions. The registry description specifies conversion using molecular weights and a summed value. The registry record does not provide analyte-specific estimates, so it is not possible to determine how much each analyte contributed to the combined endpoint.

The endpoint description contains a naming inconsistency: the primary title and the population description identify AP32914, while the calculation description mentions AP3914 in one place. The record does not clarify whether this is a typographical error or a different analyte designation. Interpretation of the combined endpoint should therefore retain the registry’s stated inconsistency rather than assume a correction.

What does a geometric mean convey?

The endpoint is described using a geometric mean, with geometric coefficient of variation as the dispersion measure. As general statistical context, geometric summaries are often used for positive measurements that are skewed, such as concentration data. They are calculated on a logarithmic scale and then expressed on the original scale. A geometric mean characterizes a multiplicative center rather than an arithmetic average. The geometric coefficient of variation describes relative variability on a multiplicative scale; it is not the same quantity as a standard deviation.

The registry record does not provide the geometric mean or geometric coefficient of variation for either treatment. It also does not state whether the treatment contrast was expressed as a ratio, difference, or another statistic. It would therefore be inappropriate to supply a numerical treatment effect or infer one from the endpoint label alone.

Why does the study structure matter?

The study is listed as sequential and non-randomized, with no masking. In general, randomization can help balance measured and unmeasured characteristics between treatment groups, while masking can reduce some forms of assessment or behavior bias. Those protections are not indicated by the listed design characteristics. The treatment sequences make the order and timing of exposure relevant to interpretation. The registry record does not report the statistical model, any adjustment for period or sequence, or how within-participant dependence was handled.

Because the treatments are listed as sequences, paired data may be a relevant consideration in general, but the registry record does not state whether the analysis used paired observations or confirm the number of participants with usable data under both conditions. No analytic method should be attributed to the study without that information.

How should uncertainty and tests be read?

A confidence interval is a general way to communicate statistical uncertainty around an estimated effect. A narrow interval indicates greater precision under the model assumptions than a wide interval; the interval alone does not establish clinical importance. A p-value, when reported, addresses compatibility of data with a specified null model, not the probability that a treatment is effective. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

The registry lists 7 outcome measures and 4 analyses, but the detailed methods and results for these are not reported in the information available in the registry record. It does not describe a prespecified multiplicity adjustment, interim analyses, a missing-data method or a detailed statistical analysis plan. Those absences limit assessment of how analyses were selected, how uncertainty was quantified and how the reported endpoint relates to any other outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures and 4 analyses, but does not report the detailed statistical plan governing those outcomes and analyses. It does not state whether a particular endpoint hierarchy was prespecified, whether any multiplicity adjustment was used, or how the family of statistical tests was defined. These details matter because conducting multiple tests can increase the chance of at least one nominally unusual result. Without a reported approach, the interpretation of any isolated test result would require caution; the record does not report a primary-endpoint test result in any case.

Missing-data handling is also not reported in the registry record. The primary population is described as a PK Set: participants who complied sufficiently with the protocol and had an evaluable PK profile. This definition indicates that the primary endpoint concerns evaluable pharmacokinetic data rather than necessarily all enrolled participants. However, the registry record does not report the number included in this set, the reasons any data were considered unevaluable, or whether missing observations were excluded, imputed or handled through another method.

The record does not describe interim analyses, stopping rules or a detailed statistical analysis plan. These omissions do not establish that such procedures were absent; they mean their presence and details are not reported in the registry record. The listed enrollment of 24 should not be read as the number analyzed for every endpoint. No endpoint-specific analysis count is reported, so the relationship between enrollment and the primary analysis population cannot be assessed.

11. 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 non-serious adverse event terms

For each listed treatment group, 12 participants were at risk for serious adverse events and 0 were reported as affected. The record also lists 0 deaths in each group. These are the serious-event and death counts recorded for Part 1 Treatment A, Part 1 Treatment B, Part 2 Treatment C and Part 2 Treatment D.

The count for other adverse events differs across the listed groups: 1 participant in Treatment A, 4 in Treatment B, 9 in Treatment C and 10 in Treatment D were reported as affected, with 12 at risk in each group. These are counts, not estimates of a causal treatment effect. The groups belong to a sequential, non-randomized study, and Part 1 and Part 2 have different TAK-788 doses and coadministered drugs. Their counts should not be treated as a like-for-like randomized comparison.

Zero serious events recorded does not establish that a treatment has no serious risks. It describes what was reported among the participants at risk in this study. The registry record does not provide serious adverse event terms, and the listed top serious terms are empty. It also does not provide additional details about event timing or attribution. The counts should therefore be read as a limited description of reported events, not as a complete safety assessment.

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

This study is designed to characterize pharmacokinetic interactions: how TAK-788 exposure, including exposure to its active metabolites, changes when itraconazole or rifampin is given as part of the treatment sequence. The stated primary question focuses more narrowly on the combined molar Cmax comparison between Treatment B and Treatment A in Part 1. That is a pharmacokinetic question, not a direct test of clinical benefit.

The registry record does not report the numerical primary endpoint result, the treatment contrast, a confidence interval or a p-value. It is therefore not possible to say whether the combined Cmax was higher or lower under Treatment B, by how much it differed, or how precisely the difference was estimated. The same absence of numerical outcome information prevents an assessment of the rifampin comparison from this record.

Even a reported difference in a pharmacokinetic measure would describe drug exposure under the studied conditions. As general context, the clinical implications of an exposure change depend on other evidence and cannot be established from Cmax alone. The registry record does not identify a clinical threshold for the combined measure or report clinical outcomes that would link the endpoint to patient benefit or harm.

The study enrolled healthy adults and was non-randomized, sequential and unmasked. These design features define the scope of the evidence. The record does not support generalizing the results to other populations or treatment settings, and no such generalization can be made from the study description alone. The separate parts also involve different TAK-788 doses, so the two coadministration questions should not be collapsed into one estimate.

The adverse event counts describe events reported in the treatment groups, including no serious adverse events and no deaths recorded in those groups. They do not establish that serious risks are absent. Overall, the registry entry identifies the study’s pharmacokinetic objective and treatment schedules, but the numerical efficacy-related pharmacokinetic result needed to characterize the primary comparison is not reported in the registry record.

13. Why This Trial Matters Statistically

Drug-drug interaction studies address whether exposure to a study drug changes when another drug is given alongside it. This study’s structure makes that question explicit for TAK-788 with itraconazole and with rifampin, using pharmacokinetic measurements in healthy adult participants. The primary endpoint focuses on a combined molar peak concentration for TAK-788 and its active metabolites, rather than on a clinical outcome.

Statistically, the study is a useful example of why design labels and endpoint definitions need to be considered together. The registry lists a sequential model, non-randomized allocation and no masking. Those characteristics differ from a randomized comparison of concurrent groups and make the treatment sequence important context. The separate parts also have different TAK-788 doses and coadministered drugs, so they address distinct questions.

The record also illustrates the value of reporting estimates with uncertainty and specifying the analysis population and model. A geometric mean and geometric coefficient of variation are named as the endpoint summary and dispersion measure, but the numerical endpoint findings are not reported in the registry record. Without an estimate and an uncertainty measure, readers cannot assess the direction, size or precision of the intended comparison.

Finally, the study shows why a registry description is not a substitute for a complete statistical report. The record identifies the primary measure, timeframe and PK population definition, while details about the analysis method, missing data and multiplicity are not reported. Those details are important for judging how results were obtained and what conclusions they can support.

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 most consequential limitation of the registry record for statistical interpretation is that it does not report the numerical primary endpoint result. No treatment-specific geometric means, treatment contrast, uncertainty interval or test result is reported. The direction, magnitude and precision of the Part 1 comparison therefore cannot be evaluated.

The statistical analysis method is not reported. The record does not specify the model used for the sequential comparison, how treatment order was handled, whether observations were paired, or whether any covariates or adjustments were used. The PK Set is defined by sufficient protocol compliance and an evaluable profile, but the number of participants analyzed and the handling of missing or unevaluable observations are not reported.

The registry record does not describe a prespecified multiplicity strategy, interim analyses or a detailed statistical analysis plan. Although it lists 7 outcome measures and 4 analyses, it does not provide the full details needed to assess the relationship among them. A trial-specific sample-size justification is also not reported. The stated planning assumptions are illustrative calculations based on an observed effect; they do not constitute evidence about the study’s original design rationale.

The endpoint description has an unresolved metabolite naming inconsistency: AP32914 is named in the primary endpoint and elsewhere, while AP3914 appears in the calculation description. The record does not clarify this discrepancy. In addition, the treatment descriptions are incomplete, so some schedule details, including the full washout information, are not reported in the registry record.

Finally, the non-randomized, unmasked sequential design and healthy adult population limit the scope of interpretation. The adverse-event counts are descriptive, with no serious events or deaths recorded, but they cannot establish the absence of risk. These limitations constrain conclusions without implying that unreported procedures or results were necessarily absent from the completed study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants — NCT03928327.
• Registry record last updated 2020-08-21; status last verified 2020-08.
• Results first posted 2020-08-21.
• 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 a completed Phase 1 study of oral TAK-788 in 24 healthy adult participants. It lists non-randomized allocation, no masking and a sequential model. Part 1 examined TAK-788 with itraconazole, and Part 2 examined TAK-788 with rifampin.

The primary endpoint is the combined molar Cmax of TAK-788 and its metabolites in the Treatment B versus Treatment A comparison in Part 1. The endpoint is described using a geometric mean and geometric coefficient of variation. The registry record defines a PK Set of sufficiently compliant participants with an evaluable PK profile, but does not report the number analyzed.

Numerical results for the primary endpoint, uncertainty estimates, and detailed analysis methods are not reported in the registry record. Serious adverse event counts and deaths were 0 in each listed treatment group; other adverse event counts were 1, 4, 9 and 10, respectively, with 12 at risk in each group. The sequential, non-randomized design and incomplete statistical reporting are important context for interpreting these records.