BLI400-302: A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BLI400-302: A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults (NCT02819297), a randomized phase 3 study. The primary outcome is Treatment Response.

2. Clinical Question

The registry describes the study objective as evaluating the safety and efficacy of daily BLI400 Laxative versus placebo in constipated adults. The clinical question is expressed statistically as a comparison of the proportions who achieved the prespecified response definition. A participant counted as a weekly responder by having at least 3 complete spontaneous bowel movements (CSBMs) in a week and an increase from baseline of more than 1 CSBM in that week. The overall endpoint then required meeting the weekly definition often enough across the treatment period, including during its final weeks.

This is a binary endpoint: each participant either met the overall response definition or did not. The registry reports 77 responders among 294 participants in the BLI400 Laxative group and 39 among 302 in the placebo group. These counts describe the modified intention-to-treat analysis population for the primary endpoint, not every enrolled participant. The registry record does not report further details about how missing weekly observations were handled or how the modified population was constructed.

3. Trial Design

NCT02819297 is a completed phase 3 randomized trial sponsored by Braintree Laboratories. It compared BLI400 Laxative with BLI400 placebo in adults with constipation, including chronic idiopathic constipation. The registry lists a parallel-group model and quadruple masking. These labels describe the broad design; which specific roles were masked and the practical procedures used to maintain masking are not reported in the registry record.

The registry records enrollment of 1020 participants. The study start is listed as 2016-06 and primary completion as 2017-06. The intervention descriptions identify BLI400 Laxative and BLI400 placebo, and the study summary describes the active treatment as a daily dose. The endpoint timeframe was 12 weeks. More detailed information about dose, treatment administration, eligibility criteria, allocation procedures, site organization, or follow-up beyond the endpoint timeframe is not reported in the registry record.

The primary outcome was treatment response, recorded as a count of participants meeting a binary definition. Its analysis population was modified intention-to-treat, excluding subjects with significant protocol violations. The registry reports 294 participants in the active-treatment outcome group and 302 in the placebo outcome group. These are the denominators shown for the primary endpoint; the record does not explain the difference between these group sizes and overall enrollment.

One primary outcome measure and one sponsor-reported analysis are posted, and no secondary outcomes are posted. The sponsor’s reported comparison used a Cochran-Mantel-Haenszel method and was classified as a superiority analysis. Details of any stratification variables, prespecified covariates, or other analysis-plan elements are not reported in the registry record. The record also does not report the trial’s original sample-size justification or design assumptions.

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: 1020 subjects were consented and entered into a two-week run-in period to confirm constipation status (subjects were required to average \< 3 complete spontaneous bowel movements per week). Following the run-in period, 603 subjects qualified for randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: modified ITT population - excludes subjects with significant protocol violations

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: ITT Population

6. Primary Endpoint

The registry lists the primary outcome as Treatment Response, measured over 12 weeks.

The primary endpoint counts participants who met a sustained weekly-response definition during 12 weeks of treatment. First, a weekly responder had to record at least 3 complete spontaneous bowel movements (CSBMs) and an increase from baseline of more than 1 CSBM in that week. The overall endpoint required a participant to be a weekly responder in at least 9 out of 12 weeks, with at least 3 of those response weeks occurring in the final 4 weeks of treatment.

This endpoint combines a threshold for bowel-movement frequency with a change from the participant’s baseline, then requires that response to recur over much of the treatment period and near its end. A sustained definition can represent a different clinical pattern from a response observed in only one or a few weeks. The registry record does not provide the rationale for selecting these exact thresholds or the endpoint’s validation history, so those aspects cannot be assessed from the posted information.

For analysis, the endpoint is binary at the participant level: the participant is counted as a responder or a non-responder. The posted counts are 77 of 294 for BLI400 Laxative and 39 of 302 for placebo. The modified intention-to-treat population excludes subjects with significant protocol violations, but the registry record does not specify the rules for handling missing weekly observations, incomplete diaries, or other departures from the endpoint definition. Those details matter because this outcome depends on observations across multiple weeks.

7. Results Posted in the Registry

• BLI400 Laxative: 26.2% (77/294) versus 12.9% (39/302) on control; risk difference 13.3 percentage points (95% CI 7.0 to 19.6), risk ratio 2.03 (1.43–2.88); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is binary because each participant is classified as meeting or not meeting the overall response rule. For a binary endpoint, the basic quantities are the number meeting the definition and the number assessed in each group. The registry reports 77 of 294 in the BLI400 Laxative group and 39 of 302 in the placebo group. These counts are the basis for the unadjusted comparison; they do not show the week-by-week data used to determine each participant’s status.

What does the unadjusted risk difference represent?

The recalculated risk difference is 0.133, with an interval from 0.070 to 0.196. It compares the observed response proportions on an absolute scale. The estimate is calculated from the posted summary counts without adjustment for other variables. It is therefore distinct from the sponsor’s Cochran-Mantel-Haenszel test, which is the analysis reported by the registry as the sponsor’s comparison. The registry does not post the sponsor’s adjusted effect estimate or its confidence interval.

Other relative measures are also listed in the posted comparison: the risk ratio is 2.028, with limits 1.429 and 2.878, and the odds ratio is 2.393, with limits 1.564 and 3.66. These measures express group contrast on relative rather than absolute scales. Relative measures can look different from an absolute difference because they answer different questions. The registry record does not state a confidence level for these intervals.

What does the Cochran-Mantel-Haenszel method do?

General statistical explanation: the Cochran-Mantel-Haenszel method is commonly used to compare categorical outcomes while accounting for specified strata. If a trial has stratification variables, this approach can combine information across strata rather than treating all participants as one undivided group. The registry names this method but does not report the strata or the details needed to determine how it was implemented. The sponsor’s reported p-value is <0.001, and the analysis is labeled as a superiority comparison.

A test result and an effect estimate serve different purposes. A test evaluates compatibility with a null hypothesis under the method’s assumptions; an estimate describes the direction and scale of the observed contrast. The sponsor’s analysis has a reported p-value but no posted estimate or interval. The recalculated unadjusted risk difference supplies an effect estimate based on the summary counts, but it does not reproduce any unreported adjustment in the sponsor’s analysis.

Why distinguish the analyses?

Adjustment can matter when a comparison accounts for design features or other variables, while a simple unadjusted calculation uses only the group counts and denominators. Since the registry does not provide the sponsor’s adjusted estimate, the two results should be presented according to what each actually represents. No discrepancy is flagged in the record. The unadjusted p-value is also <0.001, as is the sponsor-reported p-value, but matching threshold statements do not mean the methods or estimates are interchangeable.

General statistical explanation: over-dispersion is a concern when observed variability is greater than a model assumes, which can make standard errors too small if the model does not account for it. The posted primary endpoint is a participant-level binary outcome, and no over-dispersion model or diagnostic is reported. It would be inappropriate to infer that such an issue arose or was addressed in this trial.

What information is missing about the analysis?

The registry record does not report the trial’s original statistical analysis plan, the original sample-size justification, or whether there were interim analyses. It does not describe missing-data handling for the weekly response endpoint, detailed rules for the modified intention-to-treat population, or the sponsor analysis’s stratification variables. These omissions prevent a full assessment of whether the reported analyses followed a prespecified plan and how sensitive the result may be to analysis choices. They do not alter the fact that the registry posts the stated counts and sponsor p-value.

General statistical explanation: a confidence interval gives a range of values compatible with the data and the interval procedure, under its assumptions. It is not a guarantee that the true effect lies within the displayed range. Precision depends in part on the amount of information and the variability of the data. For the recalculated risk difference, the reported interval communicates uncertainty around the unadjusted estimate; the registry does not identify its confidence level.

The endpoint’s repeated-week structure also makes the definition and missing-data rules relevant. A participant’s overall status depends on observations across 12 weeks, and the rule requires response in the final 4 weeks as well as across the full treatment period. The registry gives the definition but not the procedures for incomplete weekly records. No assumptions about those procedures should be attributed to the trial based solely on the posted record.

10. Confidence Intervals and Precision

The unadjusted risk difference is 0.133, with reported interval limits of 0.070 and 0.196. The interval provides a way to express uncertainty around the estimated absolute contrast between the posted groups. Its lower and upper limits are both above zero. The registry record does not report the confidence level, so the interval should not be labeled with a conventional confidence percentage unless that information is available elsewhere in the record.

General statistical explanation: a confidence interval is produced by a procedure designed to capture the underlying quantity at a stated rate over repeated use, assuming the model and sampling conditions are appropriate. It is not a range containing a known fixed effect with a probability that can be read directly from one study. A narrower interval indicates greater precision than a wider interval on the same scale, but precision alone does not establish clinical importance or remove bias.

The interval applies to the recalculated unadjusted risk difference, not to the sponsor’s Cochran-Mantel-Haenszel analysis. The sponsor’s reported result includes p <0.001 but no effect estimate or confidence interval in the registry record. The relative measures also have reported limits, but the record does not specify the confidence level for those intervals either. Keeping the unadjusted and sponsor-reported results distinct avoids implying that they estimate uncertainty in exactly the same way.

The posted group counts are 294 and 302 for the primary endpoint. The endpoint is based on weekly response over 12 weeks, but only the final participant-level counts are reported. Without the week-level data and missing-observation rules, it is not possible to evaluate how alternative handling choices might affect the estimate. The displayed interval quantifies sampling uncertainty under its calculation; it does not account for every possible source of uncertainty in trial conduct, measurement, or analysis.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect and use two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. Each row asks how many participants per arm would be needed under a specified fraction of the observed effect as the effect to detect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the stated effect, under the listed assumptions, if that effect were the true effect and the model assumptions held. The 90% power column gives the corresponding illustration for a 90% chance. These are prospective planning quantities, not measures of what the completed trial achieved.

For planning based on 100% of the observed effect, the figures are 139 participants per arm for 80% power and 186 participants per arm for 90% power. Planning for 75% of the observed effect gives 232 participants per arm for 80% power and 310 for 90% power. Planning for 50% of the observed effect gives 484 participants per arm for 80% power and 647 for 90% power. The pattern illustrates the general principle that smaller effects are harder to distinguish from random variation and therefore require more participants, all else equal.

These figures are planning illustrations, not observed power. They do not indicate the probability that the trial’s result is true, and they do not replace the registry’s reported outcome counts, effect estimate, or p-value. The original design may have used assumptions not reported in the registry record, so these illustrations should not be read as a reconstruction of the trial’s actual planning process.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.129; treatment proportion p₁ = 0.262; average p̄ = 0.196.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5609 = 1.0993.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5530 = 0.4654.
4. n = (1.0993 + 0.4654)² / (0.1328)² = 138.9, rounded up to 139 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.129139072847682                          # control proportion
p1 <- 0.261904761904762                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2819297)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 139 (80% power), 186 (90% power)
 75% of observed effect: n per arm = 232 (80% power), 310 (90% power)
 50% of observed effect: n per arm = 484 (80% power), 647 (90% power)
power.prop.test: 138.9 
Simulated power at n = 139 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor-reported analysis is a Cochran-Mantel-Haenszel superiority comparison between BLI400 Laxative and placebo, with p <0.001. The registry does not report an effect estimate or confidence interval for that analysis, nor does it identify the strata used. The sponsor’s result should therefore be described as a test result rather than as a reported adjusted estimate of the treatment contrast.

The recalculated result is a simple unadjusted comparison of the posted counts: 77 of 294 participants in the BLI400 Laxative group and 39 of 302 in the placebo group. Its risk difference is 0.133, with interval limits of 0.070 and 0.196, and its unadjusted p-value is <0.001. This calculation uses the group summaries and does not reproduce any stratification or adjustment that may be part of the sponsor’s method.

No discrepancy is flagged between the registry result and the recalculation. The posted p-value threshold is the same for both analyses, but that does not make the analyses methodologically identical. The sponsor’s own analysis takes precedence if a discrepancy is flagged; in this record, no such discrepancy is flagged. The unadjusted estimate is useful as a transparent description of the posted counts, while the sponsor’s named method remains the registry’s reported analysis.

14. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome measure and one sponsor-reported analysis. It posts no secondary outcomes. The primary endpoint is treatment response over 12 weeks, and the sponsor’s analysis is labeled as a superiority comparison with p <0.001. The registry record does not report a multiplicity-control procedure, a hierarchy among outcomes, or an adjustment for testing multiple endpoints or comparisons.

General statistical explanation: multiplicity arises when several hypotheses are tested, because the chance of at least one apparently notable result can increase as the number of tests grows. Prespecified testing strategies can control that issue, but the registry information does not establish whether any such strategy was used. With no secondary outcomes posted and no analysis-plan details, the handling of multiplicity cannot be evaluated from the record.

The primary analysis population is described as modified intention-to-treat and excludes subjects with significant protocol violations. The registry does not define what constituted a significant violation, report the number excluded for that reason, or provide a participant flow description for the primary endpoint. The posted primary outcome denominators are 294 for BLI400 Laxative and 302 for placebo, while overall enrollment is 1020. The record does not explain the relationship between enrollment and the endpoint analysis groups.

Missing-data procedures are not reported in the registry record. This is relevant because the endpoint requires repeated weekly observations and includes a requirement for response in the final treatment weeks. The registry provides no information about how incomplete diaries, missed visits, withdrawal, or other missing weekly observations were classified. It also does not report sensitivity analyses addressing different missing-data assumptions.

The record does not report interim analyses or the trial’s original statistical analysis plan. It is therefore not possible to assess from the registry whether the analysis population, testing strategy, or missing-data methods were prespecified in detail. These are limitations of the posted information; they do not establish that the trial lacked a protocol or analysis plan.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebrovascular accident (0.3%), bile duct stone (0.3%), blood pressure increased (0.3%), forearm fracture (0.3%), arthralgia (0.3%).

The posted serious adverse event counts are 3 among 299 participants at risk in the BLI400 Laxative group and 8 among 304 participants at risk in the placebo group. No deaths are reported in either group. These figures describe the recorded counts and denominators; they do not provide detail about the timing, duration, severity beyond the serious-event classification, or investigator assessment of relatedness.

The registry also lists six serious-event terms, each with a posted value of 0.3%: cerebrovascular accident, bile duct stone, blood pressure increased, forearm fracture, arthralgia, and coronary artery disease. The record does not clarify whether these terms represent all serious events or a selected list of terms. It also does not provide event counts by term in the posted information, so the terms should not be used to infer more detailed event distributions.

Other adverse events are reported for 42 of 299 participants in the BLI400 Laxative group and 33 of 304 in the placebo group. The registry’s category is “other” adverse events; further definitions and details are not reported in the registry record. Serious-event counts and other adverse-event counts are separate categories in the posted results and should not be combined. These counts are descriptive and do not, on their own, establish causation or provide a complete assessment of comparative safety.

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

The posted results show that more participants in the BLI400 Laxative group met the registry’s specified treatment-response definition than in the placebo group: 77 of 294 compared with 39 of 302. The unadjusted risk difference is 0.133, with an interval from 0.070 to 0.196, and the unadjusted p-value is <0.001. The sponsor-reported Cochran-Mantel-Haenszel superiority analysis also reports p <0.001.

The result concerns a particular endpoint: meeting a weekly CSBM threshold, achieving an increase from baseline, and sustaining the weekly response for at least 9 out of 12 weeks, including at least 3 of the final 4 weeks. It does not directly report every symptom, outcome, or aspect of experience that may matter to participants. No secondary outcomes are posted, so the registry record does not support broader conclusions about other efficacy measures.

The result does not show how the endpoint would have been affected by different rules for missing weekly observations, because those rules are not reported. It also does not establish the sponsor analysis’s adjusted effect size, since the registry gives its p-value but not an effect estimate or interval. The unadjusted recalculation and sponsor test answer related but not identical statistical questions.

The safety record reports serious adverse events in both groups and no deaths in either group. The posted counts are limited information: event timing, relatedness assessments, and further details are not reported. Those counts should be read alongside the efficacy outcome rather than treated as a complete safety evaluation.

General interpretation: a randomized comparison can help distinguish group outcomes under the conditions of the trial, while uncertainty remains about the precision and applicability of the findings. The registry record does not provide enough detail to resolve all questions about eligibility, analysis procedures, missing data, or external applicability. These results describe the posted data and do not constitute medical advice or a recommendation for any individual.

17. Why This Trial Matters Statistically

This trial is statistically informative because it reports a randomized, parallel-group comparison with a clearly described binary primary endpoint and participant counts in both groups. The response rule has a repeated-measure component: a participant must meet a weekly criterion over much of the 12-week period and also meet it during the final treatment weeks. That makes the endpoint more specific than a single measurement at one visit.

The posted result supports a useful comparison of statistical summaries. The sponsor’s analysis is named as a Cochran-Mantel-Haenszel superiority test, while the posted recalculation gives an unadjusted risk difference of 0.133 and interval limits of 0.070 and 0.196. Both reported p-values are <0.001. Recognizing that these methods differ is important: a p-value alone does not communicate the size of the contrast, and an unadjusted estimate should not be mistaken for an adjusted sponsor estimate.

The record also illustrates why statistical precision and planning assumptions are distinct. The planning illustrations show that detecting smaller fractions of the observed effect calls for more participants per arm under the stated assumptions. Those illustrations do not reveal the trial’s original design rationale, which is not reported, and they are not evidence of the completed trial’s achieved power.

Finally, the record’s gaps are statistically relevant. Missing-data handling, the rules defining the modified intention-to-treat population, the sponsor analysis strata, and multiplicity procedures are not reported. These details influence how readers can assess the robustness and reproducibility of a result. Identifying those limits is part of interpreting the evidence, not a claim that the trial’s procedures were inappropriate.

18. 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.

Several trial-specific details needed for a fuller statistical assessment are not reported in the registry record. The original sample-size justification and design assumptions are not reported, so the planning illustrations cannot be treated as a reconstruction of the trial’s intended power or enrollment rationale. Interim analyses are also not reported.

The sponsor analysis is identified as Cochran-Mantel-Haenszel, but the registry does not give its stratification variables, adjusted effect estimate, or confidence interval. The unadjusted recalculation is based on the posted participant counts and does not show whether adjustment would materially change the estimated contrast. The confidence level for the recalculated interval is not reported.

The modified intention-to-treat population excludes subjects with significant protocol violations, but the record does not explain the violation criteria or the number excluded. Enrollment is listed as 1020, while the primary outcome denominators are 294 and 302; the registry does not describe participant flow or explain the relationship among these counts. Missing weekly observations and their handling are not reported, despite the endpoint requiring repeated assessments over 12 weeks and response in the final treatment weeks.

No secondary outcomes are posted, and multiplicity procedures are not reported. The registry also lacks details about the operational masking procedures, allocation implementation, and other design features that could inform risk-of-bias assessment. For safety, serious-event counts and selected terms are posted, but event timing, relatedness, and additional clinical detail are not reported. These limitations restrict what can be concluded from the registry record without implying that unreported procedures were absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: BLI400-302: A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults — NCT02819297.
• Registry record last updated 2020-07-27; status last verified 2020-07.
• Results first posted 2020-06-26.
• 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.

22. Record Summary

NCT02819297 is a completed phase 3 randomized, quadruple-masked, parallel-group trial sponsored by Braintree Laboratories. It evaluated BLI400 Laxative versus placebo in adults with constipation, including chronic idiopathic constipation. Enrollment was 1020; the study start is listed as 2016-06 and primary completion as 2017-06.

The primary endpoint was treatment response over 12 weeks, defined by repeated weekly CSBM criteria. The modified intention-to-treat outcome counts were 77 of 294 for BLI400 Laxative and 39 of 302 for placebo. The unadjusted risk difference was 0.133, with interval limits of 0.070 and 0.196; the unadjusted p-value was <0.001. The sponsor-reported Cochran-Mantel-Haenszel superiority analysis reported p <0.001.

Serious adverse events were reported for 3 of 299 participants at risk in the BLI400 Laxative group and 8 of 304 in the placebo group; no deaths were reported in either group. No secondary outcomes are posted. Details of missing-data handling, multiplicity, and the original sample-size justification are not reported in the registry record.