A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants (NCT03482453), a randomized phase 1 study. The primary outcome is Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The registry record describes a Phase 1 study in healthy participants, not a trial evaluating clinical benefit in people with a disease. Its aims cover multiple questions: whether single oral doses were tolerable, how TAK-788 and its active metabolites behaved in plasma, whether a low-fat meal affected TAK-788 pharmacokinetics, and how the test capsule formulation compared with the reference formulation.

The primary outcome addresses a safety question in Part 1. It counts participants who experienced at least one treatment-emergent adverse event, rather than counting every event or measuring event severity. The posted counts can describe what was observed in each group, but they do not by themselves establish a causal difference between TAK-788 and placebo or quantify a comparative effect with statistical precision.

3. Trial Design

This was a randomized, triple-masked, sequential Phase 1 study. The registry record lists enrollment of 69 healthy participants and a completed status. The recorded study start was 2018-03-28, and primary completion was 2018-12-22. The sponsor was Millennium Pharmaceuticals, Inc.

The study had three parts. Part 1 used sequential cohorts to evaluate single oral TAK-788 doses under fasted conditions. Participants in the five dose cohorts received TAK-788 or matching placebo; later cohorts proceeded following review of safety data from the preceding cohort. The posted dose groups were 20 mg, 40 mg, 80 mg, 120 mg, and 160 mg, alongside pooled placebo. This sequential arrangement means the cohorts were not simply a set of concurrent dose groups.

Part 2 used an open-label crossover to evaluate food effects. Participants received TAK-788 under fed conditions with a low-fat meal and under fasted conditions in different intervention periods, with at least 7 days of washout between periods. The listed groups include 120 mg and 160 mg fed and fasted treatments. Part 3 was also a crossover, comparing TAK-788 DiC A, the reference, with TAK-788 DiC B, the test, at 160 mg under fasted conditions, with at least 7 days of washout.

The registry record describes the design as randomized and triple-masked overall, while the later crossover parts are specifically described as open-label. The allocation method, masking procedures by part, randomization sequence, and operational details of the safety reviews are not reported in the registry record. The protocol’s planned sample-size justification and detailed statistical analysis plan are also not reported in the registry record.

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 3 parts study to receive: TAK-788 as a single rising dose of 20 milligram (mg), 40 mg, 80 mg, 120 mg, 160 mg in Part 1; TAK-788 in a 2-way cross-over design with or without a low-fat meal in Part B; or in a 2-way cross-over sequence to receive TAK-788 drug in capsule (DiC) A or B in Part 3.

Only the first 6 of 12 groups are shown.

Part 1 (1 Day)

Parts 2, 3 Intervention Period 1 (1 Day)

Reasons for not completing this period:

Parts 2, 3 Washout Period (7 Days)

Parts 2, 3 Intervention Period 2 (1 Day)

Analysis population for the primary outcome, as defined in the registry: The safety set included all participants who received any study treatment.

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 set included all participants who received any study treatment.

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), measured over Baseline up to 30 days after the last dose of study drug (Day 31).

The primary endpoint is the number of participants reporting one or more treatment-emergent adverse events in Part 1. The registry record defines the observation period as baseline up to 30 days after the last dose of study drug (Day 31). The primary safety population includes all participants who received any study treatment.

This endpoint summarizes whether participants experienced an event during the specified period. Because it counts participants with at least one event, a participant with multiple events still contributes to the participant count as an affected participant. The measure does not describe the total number of events, their duration, their severity, or their relationship to treatment. Those details require separate outcome reporting.

Counting participants with adverse events is useful in an early-phase study because tolerability and safety are central questions while doses and pharmacokinetic properties are being characterized. The count also allows the observed experience in the dose cohorts to be read alongside the pooled placebo group. However, a count alone is not a rate or a comparative effect estimate. The group sizes differ, and the posted primary outcome does not include confidence intervals or a formal comparison. The endpoint therefore supports a descriptive account of reported events, not a precise estimate of how treatment changes event risk.

The record also lists pharmacokinetic outcomes, including maximum observed plasma concentration, time to maximum concentration, areas under the concentration-time curve, and terminal disposition half-life for TAK-788 and its active metabolites. Numerical results for those outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure: a participant either reported one or more treatment-emergent adverse events during the defined follow-up, or did not. Reporting the number affected is a direct way to describe the observed experience in each group. It is different from reporting the total number of events, because multiple events in a participant do not increase the count of affected participants beyond that participant’s inclusion in the endpoint.

What do the counts tell us?

A count should be read together with its group size. The posted Part 1 summaries give the count and denominator for pooled placebo and each TAK-788 dose cohort. Those figures show how many participants were included and how many met the endpoint, but the registry record does not post an uncertainty interval for each group. A confidence interval is a statistical range intended to express the uncertainty around an estimate under a specified method and assumptions. With small groups, uncertainty can be substantial; without posted intervals, readers should not treat the observed counts as precise estimates of underlying event frequency.

A comparison between groups usually requires an effect estimate, such as a difference or ratio, together with uncertainty and an analysis method. No such comparative estimate is reported for this binary endpoint. The record states that values were missing or not estimable for a two-arm comparison. Accordingly, the posted figures support descriptive reading rather than a formal comparative claim. No additional calculation should be inferred from the group counts.

Why does the design matter?

Part 1 was sequential: later cohorts followed review of safety data from the preceding cohort. This design provides a structure for dose escalation, but it also means dose cohorts were assembled in sequence rather than as one fully concurrent set of groups. Changes over time, cohort composition, or other design features could matter when interpreting between-cohort differences. The registry record does not report details sufficient to assess those factors or the precise rules for safety review.

Part 2 and Part 3 used crossover arrangements. In a crossover, the same participant receives treatments in different periods, allowing treatment conditions to be compared within participants. The record describes at least 7 days of washout between periods. Analysis of crossover data commonly needs to account for paired observations and possible period or sequence effects. The statistical methods used for those outcomes are not reported in the registry record, and the Part 1 adverse-event counts should not be mistaken for results from those crossover comparisons.

What does the planning information mean?

The registry record describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are hypothetical planning exercises: they describe the sample size that might be needed under stated assumptions to detect an effect of a specified fraction of the observed effect. They are not observed power, do not establish the probability that the study detected an effect, and are not evidence that the trial was designed around those assumptions. The trial’s own sample-size justification is not reported in the registry record.

For this binary endpoint, the record indicates that a two-arm comparison was not estimable, so there are no usable comparative values on which to base the planning illustrations. No planning sample size should be interpreted as an observed trial result. Planning calculations also depend on their assumptions; different assumptions about the effect, variability, allocation, or analysis method can lead to different planning requirements.

What inferential details are unavailable?

The registry record does not report a confidence interval, p-value, test specification, effect estimate, covariate adjustment, or detailed statistical analysis plan for the primary endpoint. It also does not report how missing outcome data were handled, whether sensitivity analyses were conducted, or whether an interim analysis was planned. The absence of those details prevents reconstruction of a formal inferential analysis from the posted counts.

In general, over-dispersion matters when observed variability is greater than a statistical model expects; a model that ignores it can give uncertainty estimates that are too narrow. That issue is not identified as part of the analysis for this binary participant count, and the methods used are not reported in the registry record. For the same reason, no particular model or variance adjustment should be attributed to the trial.

The record lists 6 analyses and 23 outcome measures, but a count of analyses does not specify the methods or comparisons used. The posted primary result is best interpreted at the level it supports: a set of observed participant counts in Part 1, without a reported comparative estimate or its uncertainty.

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("Part 1: Pooled Placebo", "Part 1 Cohort 1: TAK-788 20 mg", "Part 1 Cohort 2: TAK-788 40 mg", "Part 1 Cohort 3: TAK-788 80 mg", "Part 1 Cohort 4: TAK-788 120 mg", "Part 1 Cohort 5: TAK-788 160 mg")
n      <- c(10, 6, 6, 6, 6, 6)
events <- c(2, 2, 3, 4, 3, 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  Part 1: Pooled Placebo  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8
ARM  Part 1 Cohort 1: TAK-788 20 mg  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Part 1 Cohort 2: TAK-788 40 mg  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Part 1 Cohort 3: TAK-788 80 mg  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1
ARM  Part 1 Cohort 4: TAK-788 120 mg  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Part 1 Cohort 5: TAK-788 160 mg  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 23 outcome measures, 6 analyses, and 9 secondary outcomes posted. It does not report a multiplicity strategy for handling the several outcomes, dose cohorts, and study parts. Multiplicity is the issue that arises when many statistical questions are examined: even if each test uses a prespecified error threshold, the chance of at least one chance finding across a collection of tests can increase. Adjustments or a prespecified hierarchy can help manage that issue, but no such approach is reported in the registry record.

The record also does not report a detailed statistical analysis plan, prespecified primary comparisons beyond the named primary endpoint, interim analysis procedures, or sensitivity analyses. These details would help distinguish confirmatory analyses from exploratory descriptions and clarify how results were selected and interpreted.

The primary safety population is defined as all participants who received any study treatment. The record does not report a separate account of participants excluded from the endpoint, missing adverse-event information, or how missing data were handled. Missing-data methods can affect interpretation when outcome availability is related to participants’ treatment or experience. Without those details, the posted counts should be understood as the recorded summaries, not as evidence that missingness was absent.

The analysis populations for the PK, food-effect, and relative-bioavailability outcomes are not reported in the registry record. Nor are the numerical results for those outcomes reported in the registry record. These gaps limit assessment of how the secondary objectives were analyzed and whether their conclusions were robust to alternative assumptions.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event summaries report zero affected participants in each listed group. This includes pooled placebo and the five Part 1 dose cohorts; the Part 2 fed and fasted groups at 120 mg and 160 mg; and the Part 3 DiC A and DiC B groups. The at-risk group sizes are posted separately for each treatment condition. The record also reports zero deaths in every listed group.

A zero count means that no participant in the stated group was recorded as having the event category during the reported safety summary. It does not establish that the underlying risk is zero. With finite group sizes, uncommon events may not be observed, and the registry record does not provide confidence intervals for these serious-event summaries. The serious adverse event terms are not reported in the registry record.

These figures should also be kept distinct from the primary endpoint, which counts participants reporting one or more treatment-emergent adverse events, including events that are not serious. The non-serious event counts are posted by group, while the serious-event summaries are zero throughout. Neither set of counts on its own describes event severity in detail, exposure-adjusted rates, or causal attribution. The figures are descriptive safety information from a Phase 1 study in healthy participants.

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

The posted primary result describes the number of Part 1 participants who reported at least one treatment-emergent adverse event during the specified period. It offers a concise account of recorded events across pooled placebo and five TAK-788 dose cohorts. The accompanying serious-event summaries report zero serious adverse events and zero deaths in the listed groups.

These findings do not establish whether TAK-788 increases or decreases adverse-event risk compared with placebo. The registry record does not provide a comparative estimate, confidence interval, or formal test for the primary count outcome, and it notes that a two-arm comparison was not estimable. The counts also do not show that an absence of serious events in these groups rules out uncommon events or later risks.

The results do not answer whether TAK-788 is effective for treating a disease. Participants were healthy volunteers, and the primary endpoint is a safety count. Nor do the posted primary results answer the study’s PK questions, determine the effect of a low-fat meal, or establish relative bioavailability of the two capsule formulations. Numerical results for those objectives are not reported in the registry record.

General statistical interpretation requires attention to the design, denominators, uncertainty, and the set of outcomes examined. In this study, the sequential cohorts and small group sizes make descriptive caution important, while the absence of inferential estimates limits claims about differences between groups. The record’s completed status indicates that the study is listed as completed; it does not, by itself, establish that every planned analysis or objective has numerical results posted.

The most defensible reading is therefore narrow: the registry reports participant counts for adverse events in Part 1 and zero serious-event counts across the listed groups. Those data describe what was recorded in this study, but they do not support a broader conclusion about clinical benefit, comparative safety precision, or pharmacokinetic effects.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the outcome definition matter when reading early-phase safety data. A count of participants with at least one event is straightforward to understand, but it is not interchangeable with a total event count, a risk estimate, or a statistical comparison. Reading the counts alongside each group size is essential, and the absence of confidence intervals or comparative estimates should limit how strongly differences are interpreted.

The sequential Part 1 cohorts also make the setting of each dose relevant. The groups were advanced following review of earlier safety data, rather than being presented simply as simultaneous dose arms. That structure is important to recognize when examining apparent differences across cohorts. The later crossover parts address separate questions about food and formulation, so their treatment conditions and analysis requirements should not be merged with the Part 1 safety comparison.

The record’s combination of a stated primary safety endpoint and broader PK objectives highlights the distinction between registered aims and posted numerical findings. The registry lists PK measures and secondary outcomes, but numerical PK results are not reported in the registry record. Readers should not infer those results from the safety counts or from the study’s completion status.

Finally, the record indicates that a two-arm comparison for the binary endpoint was not estimable. This is a useful reminder that planning illustrations depend on an estimable effect and assumptions; they are not evidence of observed power or a replacement for the study’s own design justification. The trial’s own sample-size justification and detailed statistical plan are not reported in the registry record. The available information supports a transparent descriptive reading, while leaving important inferential questions unresolved.

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 primary endpoint results are counts, without reported confidence intervals, comparative effect estimates, or a formal test. The registry record indicates that values were missing or not estimable for a two-arm comparison. Consequently, the posted data do not quantify the precision of between-group differences or support a formal claim about dose-related changes.

Group sizes are small, and the dose cohorts in Part 1 were sequential. The registry record does not report enough detail about safety-review procedures, cohort timing, participant characteristics, or randomization implementation to evaluate how those features may affect comparisons. The overall enrollment of 69 should not be treated as the denominator for each endpoint; the group-specific denominators are the relevant figures for the posted summaries.

The endpoint counts whether a participant reported at least one treatment-emergent adverse event. It does not provide event-level counts, severity, duration, relationship to study drug, or exposure-adjusted summaries. Although serious-event and death counts are posted, the serious adverse event terms are not reported in the registry record.

The study aimed to assess PK, food effects, and relative bioavailability, but numerical results for those objectives are not reported in the registry record. The analysis populations, missing-data handling, multiplicity approach, detailed statistical methods, and sample-size justification are also not reported in the registry record. These omissions restrict independent assessment of the broader study aims as well as the uncertainty around the safety summaries.

Finally, the findings concern healthy participants in a Phase 1 study. They cannot be taken as evidence of treatment efficacy or as a complete account of safety in other populations or settings. The record supports description of the posted observations, not extrapolation beyond them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants — NCT03482453.
• Registry record last updated 2020-01-29; status last verified 2020-01.
• Results first posted 2020-01-29.
• 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

NCT03482453 is a completed Phase 1 randomized, triple-masked, sequential study sponsored by Millennium Pharmaceuticals, Inc. It enrolled 69 healthy participants. The study assessed single rising doses of TAK-788, food effects, and relative bioavailability of reference and test drug-in-capsule formulations.

The primary outcome was the Part 1 count of participants reporting one or more treatment-emergent adverse events from baseline through 30 days after the last dose of study drug (Day 31). The posted counts range across pooled placebo and the 20 mg, 40 mg, 80 mg, 120 mg, and 160 mg TAK-788 groups. Serious adverse event and death counts are zero in all listed groups.

Comparative estimates and uncertainty for the primary endpoint are not reported; the record indicates that a two-arm comparison was not estimable. Numerical results for the PK objectives, detailed statistical methods, missing-data handling, multiplicity strategy, and the trial’s own sample-size justification are not reported in the registry record.