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 A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults (NCT02481947), a randomized phase 3 study. The primary outcome is Complete Spontaneous Bowel Movement (CSBM) Response.

2. Clinical Question

The trial record describes a randomized, double-masked, parallel-group Phase 3 study. The registry states that its purpose was to evaluate BLI400 Laxative for safety and efficacy versus lubiprostone in constipated adults. The main statistical question is therefore a comparison between two active treatments, not a comparison with placebo or no treatment.

The endpoint is a binary participant-level outcome: each participant either met the responder definition or did not. The record reports 47 responders among 187 participants in the BLI400 Laxative arm and 56 among 199 in the lubiprostone arm. Those counts are the basis for the posted comparison, but the record does not provide enough detail to reconstruct the sponsor’s non-inferiority procedure or its decision threshold. The registry record does not report that threshold.

3. Trial Design

The registry describes NCT02481947 as a completed Phase 3 randomized, double-masked, parallel-group trial. The stated condition is chronic idiopathic constipation. Braintree Laboratories is listed as the sponsor, and enrollment is 459. The record lists the study start as 2015-05 and primary completion as 2015-11.

Participants were assigned to BLI400 Laxative or lubiprostone. BLI400 Laxative is described as 21 gm BLI400 powder, and lubiprostone as a 24 mcg capsule bid. The registry’s brief description says the study evaluated a daily dose of BLI400 Laxative for safety and efficacy versus lubiprostone. Treatment duration beyond the information used to define the 12-week endpoint is not reported in the registry record.

The primary outcome is reported for the per-protocol population. The posted endpoint counts are 187 participants in the BLI400 Laxative group and 199 in the lubiprostone group. These are the denominators used for the endpoint result, and they are distinct from the overall enrollment figure. The registry record does not provide participant-flow details that explain how the per-protocol population was formed or how participants outside it were handled.

The sponsor analysis is identified as a Chi-squared non-inferiority analysis, with p = 0.016. The registry record does not report the non-inferiority margin, the full statistical specification, or the original sample-size assumptions. The trial’s randomization procedure, allocation concealment, masking procedures, and any interim analyses are also not reported in the registry record. The posted summary therefore supports a description of the design and endpoint, but not a detailed reconstruction of the protocol or analysis plan.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol population

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 Complete Spontaneous Bowel Movement (CSBM) Response, measured over 12 weeks.

The primary endpoint is Complete Spontaneous Bowel Movement (CSBM) Response, measured as the number of participants who met a weekly responder definition over 12 weeks. A participant was a weekly responder in a week if they had at least 3 CSBMs and an increase from baseline of more than 1 CSBM in that week. To meet the primary endpoint, a participant had to be a weekly responder for at least 9 out of 12 weeks, with at least 3 of those weeks occurring in the last 4 weeks of treatment.

This is a binary endpoint at the participant level: the posted result counts participants who met the full responder rule, rather than reporting a mean number of bowel movements. Requiring the response to recur across much of the treatment period makes the outcome reflect sustained response under the trial’s definition, rather than a single favorable week. Including weeks near the end of treatment also makes later response part of the criterion.

Such a composite threshold can be useful when the clinical question concerns whether participants achieve a prespecified pattern of response. It also simplifies the comparison to a difference in the proportions meeting that rule. The threshold’s interpretation depends on the definition itself, including the weekly CSBM requirement, the change from baseline, and the number and timing of qualifying weeks. The registry reports the rule and timeframe, but additional details about how baseline CSBMs were recorded or how missing weekly observations affected classification are not reported in the registry record.

7. Results Posted in the Registry

• Lubiprostone: 28.1% (56/199) versus 25.1% (47/187) on control; risk difference 3.0 percentage points (95% CI -5.8 to 11.8), risk ratio 1.12 (0.80–1.56); unadjusted two-proportion z-test p = 0.504.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: a participant either met the CSBM responder definition or did not. For binary outcomes, a natural summary is the proportion of participants with the event in each group. The registry’s posted proportions are 0.251 for BLI400 Laxative and 0.281 for lubiprostone, based on 47 of 187 and 56 of 199 participants, respectively. A difference in proportions expresses the contrast on the absolute probability scale. The recalculated risk difference is 0.030, with the comparison oriented as lubiprostone minus BLI400 Laxative.

A confidence interval gives a range of values that are reasonably compatible with the observed data under the method used to construct it. It conveys uncertainty around an estimate, rather than stating that the true value has a specified probability of falling within that particular interval. The risk-difference interval runs from -0.058 to 0.118. Because it includes zero, the data do not rule out no difference under this unadjusted calculation. The same interval also includes differences in either direction, so the point estimate should not be read without its uncertainty.

The comparison also includes a recalculated risk ratio of 1.12, with interval limits 0.803 and 1.561, and an odds ratio of 1.166, with interval limits 0.742 and 1.834. These are alternative scales for comparing the same binary endpoint. A risk ratio compares the event proportions; an odds ratio compares the odds of the event. Neither scale removes uncertainty or replaces the need to specify which population and endpoint are being compared. The registry record does not state the confidence level associated with these recalculated intervals, so no confidence level is assigned to them.

The unadjusted p-value of 0.504 is a measure of how unusual data at least this discrepant would be under a null hypothesis of no difference, given the assumptions of the test. It is not the probability that the null hypothesis is true, and it is not a measure of clinical importance. The sponsor’s posted test is different in purpose: it is identified as a Chi-squared non-inferiority analysis and has p = 0.016. Non-inferiority testing evaluates whether the data meet a prespecified criterion for excluding an unacceptable loss relative to a comparator. The acceptable margin is central to that interpretation, but the margin and fuller test specification are not reported in the registry record. The sponsor’s own analysis therefore takes precedence over the simple recalculation, while the posted record does not allow the non-inferiority decision to be independently reconstructed.

General statistical point: a non-inferiority question is not the same as asking whether a conventional test finds a difference. The trial’s analysis must be interpreted against its prespecified margin and analysis plan. Without those details, the reported p-value can be described as a posted sponsor result but cannot be translated into a specific margin-based conclusion from this record alone.

General statistical point: binary responder outcomes compress information. They turn a participant’s pattern over time into a single classification according to the endpoint rule. This can make group comparisons straightforward, but the result depends on the cutoff and on how incomplete observations are classified. The registry specifies the weekly response threshold and the required number and timing of responder weeks; it does not report the missing-data rule used to classify participants.

The endpoint analysis population is per-protocol. Such a population consists of participants selected according to protocol-related criteria, although the criteria and exclusions used in this trial are not reported in the registry record. In general, per-protocol and intention-to-treat analyses can answer different questions, particularly in non-inferiority settings. The record does not identify an intention-to-treat primary result or explain how the reported per-protocol set was defined, so comparisons with other populations cannot be made from the posted results.

For the simple recalculation, the posted arm counts and denominators are used to describe the unadjusted binary comparison. The record also reports a sponsor analysis, which is retained as the primary report of the sponsor’s inferential analysis. Because the registry marks a discrepancy, the sponsor’s own analysis takes precedence over the recalculation. The recalculation is useful for understanding the observed counts and an unadjusted contrast, not for replacing a planned analysis or resolving undocumented analysis choices.

10. Confidence Intervals and Precision

The recalculated risk difference is 0.030, with a confidence interval from -0.058 to 0.118. The interval describes uncertainty in the absolute difference between the posted responder proportions, using the orientation lubiprostone minus BLI400 Laxative. Its inclusion of zero means that the unadjusted data are compatible with no difference, while the interval’s breadth also leaves room for differences in either direction. The estimate should therefore be read as uncertain rather than as a definitive separation between groups.

General explanation: a confidence interval combines an estimate with information about its precision. A narrower interval indicates greater precision on the scale being estimated; a wider interval indicates greater uncertainty. The interval does not describe the range of individual participant outcomes, and it does not establish that the true effect has a particular probability of lying inside it. Its interpretation also depends on the statistical method and assumptions used to calculate it.

The posted per-protocol denominators are 187 for BLI400 Laxative and 199 for lubiprostone. The registry does not provide a separate confidence interval for the sponsor’s non-inferiority test, and it does not report the non-inferiority margin. Therefore, the sponsor’s p-value of 0.016 cannot be paired with a registry-posted interval or used to judge how close the result was to a stated margin based on this record alone. The simple recalculated interval and the sponsor’s non-inferiority analysis address different inferential summaries and should remain distinct.

Precision is also limited by the information available about the analysis population and missing observations. The endpoint is reported for a per-protocol population, but participant flow and missing-data handling are not reported in the registry record. Those omissions make it harder to assess how the observed precision relates to all enrolled participants or to alternative analysis populations.

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 sample-size display is a planning illustration based on the observed effect, not the trial’s original design. Its figures are participants per arm, not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The registry record does not report the trial’s own original sample-size assumptions.

For planning at 100% of the observed effect, the display gives 3,392 participants per arm for 80% power and 4,540 participants per arm for 90% power. At 75% of the observed effect, it gives 5,976 participants per arm for 80% power and 7,999 participants per arm for 90% power. At 50% of the observed effect, it gives 13,322 participants per arm for 80% power and 17,833 participants per arm for 90% power.

In plain terms, the 80% power column gives an illustrative group size intended to yield an 80% chance of detecting the specified effect under the listed assumptions if that effect is the true one. The 90% power column applies the same idea at a higher target chance of detection. The display shows that smaller effects need more participants to detect under these assumptions. These figures are planning illustrations, not observed power; observed power is not a useful substitute for interpreting the actual estimates and their uncertainty.

The curve should be read as a visual expression of the same relationship between assumed effect size and required sample size, not as a record of participants actually enrolled. The calculations use a fraction of the observed effect, so they are conditional illustrations rather than independent evidence about a future study’s true effect. The registry record does not report whether these assumptions were used in the original protocol.

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 = 0.251; treatment proportion p₁ = 0.281; average p̄ = 0.266.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6252 = 1.2253.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6248 = 0.5259.
4. n = (1.2253 + 0.5259)² / (0.0301)² = 3,391.4, rounded up to 3,392 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 <- 0.251336898395722                          # control proportion
p1 <- 0.281407035175879                          # 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(2481947)
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 = 3,392 (80% power), 4,540 (90% power)
 75% of observed effect: n per arm = 5,976 (80% power), 7,999 (90% power)
 50% of observed effect: n per arm = 13,322 (80% power), 17,833 (90% power)
power.prop.test: 3391.4 
Simulated power at n = 3,392 per arm: 0.802 (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’s posted analysis is a Chi-squared test labeled as non-inferiority, with p = 0.016. That is the sponsor’s own analysis and takes precedence over the simple unadjusted recalculation. The recalculation uses the posted responder counts and denominators to describe the unadjusted proportions, risk difference, and p-value; it does not reproduce the sponsor’s analysis plan.

The unadjusted recalculated risk difference is 0.030, with a confidence interval from -0.058 to 0.118, and the unadjusted p-value is 0.504. These results are not a substitute for the sponsor’s non-inferiority test. A non-inferiority analysis depends on a prespecified margin and its planned statistical procedure. Neither the margin nor enough details to reconstruct the sponsor’s procedure are reported in the registry record.

The posted p-value of 0.016 can therefore be described as the sponsor’s reported non-inferiority result, but the registry record alone does not establish the exact criterion against which it was evaluated. It should not be interpreted as an ordinary test of equality or as evidence that the treatments are identical. The difference between the sponsor result and the recalculated result reflects that they are not the same analysis question, with the registry also marking a discrepancy. The sponsor analysis remains the relevant reported analysis, and the recalculation remains a descriptive, unadjusted check of the posted counts.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and one analysis, with the CSBM responder outcome identified as primary. It lists no secondary outcomes posted. This does not establish that the full protocol contained no other outcomes or comparisons; details beyond the registry record are not reported in the registry record.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, conducting multiple tests can increase the chance of at least one apparently notable result, so a planned approach to multiplicity may be important. The registry record does not report whether any multiplicity adjustment or testing hierarchy was planned. It also does not report whether the sponsor’s non-inferiority test was part of a broader sequence of analyses.

The primary endpoint is reported for the per-protocol population. The registry does not define the exact criteria for that population, identify an intention-to-treat analysis for the primary outcome, or provide participant disposition details. The endpoint counts are 47 of 187 for BLI400 Laxative and 56 of 199 for lubiprostone. Although the trial enrollment is 459, the record does not explain the relationship between overall enrollment and these per-protocol denominators through a flow of exclusions, withdrawals, or analyzed participants.

Missing-data handling is not reported in the registry record. For a response rule requiring qualifying weeks across a 12-week period, the treatment of participants with incomplete weekly measurements can affect who is classified as a responder. The record does not specify whether missing weeks were treated as nonresponse, handled through another rule, or addressed through an imputation method. The original statistical plan, including interim analyses and detailed analysis-population rules, is also not reported in the registry record.

These omissions do not invalidate the posted counts, but they constrain interpretation and reproducibility. In particular, the non-inferiority margin, analysis-population definitions, missing-data rules, and any multiplicity strategy would be needed to fully assess how the sponsor’s reported test relates to the endpoint results.

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: cellulitis of legs (0.4%), death (0.4%), stomach ulcer (0.4%).

The registry lists serious adverse events for 225 participants at risk in the BLI400 Laxative group and 229 at risk in the lubiprostone group. Serious adverse events affected 2 participants in the BLI400 Laxative group and 1 in the lubiprostone group. The record separately reports 1 death in the BLI400 Laxative group and 0 in the lubiprostone group. These counts describe the posted safety data and should be read with their group-specific denominators.

The record lists Cellulitis of legs, Death, and stomach ulcer among the top serious terms, each at 0.4%. It does not provide enough detail in this summary to assign each term to a treatment group or to establish whether terms overlap with other event listings. Serious adverse events are not the same as all adverse events; the counts concern the serious-event category reported by the registry.

General explanation: adverse-event counts are descriptive safety summaries. Their interpretation depends on event definitions, collection and coding procedures, follow-up, and the number of participants assessed. The registry record does not report detailed safety methods or group-specific participant flow beyond the at-risk denominators. These figures alone do not establish that an event was caused by a treatment, and they should not be used as a stand-alone comparison of overall safety.

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

The posted endpoint data show that 47 participants in the BLI400 Laxative group and 56 in the lubiprostone group met the CSBM responder definition in the per-protocol population. The recalculated unadjusted proportions are 0.251 and 0.281, respectively. The unadjusted risk difference is 0.030, with a confidence interval from -0.058 to 0.118. These summaries describe the observed endpoint and the uncertainty around an unadjusted comparison.

The interval includes zero and values on either side of it. That means the unadjusted result does not provide a precise estimate that excludes no difference. It also does not prove that the treatments are equivalent. A failure to distinguish the groups with an unadjusted test is not the same as demonstrating that any difference is small enough to be acceptable.

The registry separately reports a Chi-squared non-inferiority analysis with p = 0.016. This is the sponsor’s own analysis and takes precedence over the recalculation, but its full interpretation requires the non-inferiority margin and analysis details. Those details are not reported in the registry record. The sponsor result can be reported as a non-inferiority analysis with the stated p-value; the available record does not support reconstructing the test or determining the margin-based criterion.

The primary endpoint is a threshold-based measure of sustained weekly CSBM response over 12 weeks, not a summary of every bowel movement or all symptoms. Its meaning is tied to the exact responder rule: at least 3 CSBMs and an increase from baseline of more than 1 in a week, for at least 9 out of 12 weeks, with at least 3 qualifying weeks in the last 4 weeks of treatment. Other outcomes are not posted in the registry record.

The trial record also does not fully describe participant flow, missing-data handling, or the exact per-protocol criteria. These limits matter because the posted denominator is smaller than overall enrollment and because the endpoint depends on repeated weekly information. The result should therefore be understood as the reported per-protocol endpoint comparison and sponsor test, not as a complete account of every possible outcome or analysis.

17. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation depends on the question being tested, not only on the direction of the observed counts. The posted responder proportions are 0.251 for BLI400 Laxative and 0.281 for lubiprostone, and the recalculated risk difference is 0.030. The confidence interval from -0.058 to 0.118 shows why the point estimate alone cannot convey how uncertain the comparison is.

It also demonstrates the distinction between a conventional unadjusted comparison and a non-inferiority analysis. The unadjusted p-value is 0.504, while the sponsor reports a Chi-squared non-inferiority p-value of 0.016. Those values should not be read as competing answers to an identical question. Non-inferiority depends on a prespecified margin, which is not reported in the registry record. The sponsor analysis takes precedence as the reported planned analysis, but the missing margin limits independent interpretation.

The endpoint itself is a sustained-response classification across a 12-week period. This can make a complex repeated pattern easy to compare as a participant-level event, while also making the result sensitive to the chosen threshold and the handling of incomplete observations. The record does not report how missing weeks were treated, so that aspect of the endpoint cannot be assessed from the posted information.

Finally, the contrast between total enrollment and the per-protocol endpoint denominators highlights the importance of analysis populations and participant flow. A statistical estimate is most interpretable when readers can see who was analyzed, how exclusions occurred, and how missing data were handled. Those details are not reported in the registry record, making this a useful example of both what summary statistics can clarify and what registry results alone may leave unresolved.

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 full assessment are not reported in the registry record. The primary analysis is identified as per-protocol, but the criteria defining that population and the reasons participants were not included in the endpoint denominators are not given. The record reports enrollment of 459, whereas the primary endpoint denominators are 187 and 199; it does not provide a participant-flow account that reconciles these figures.

The missing-data rule is also not reported. This is particularly relevant to an endpoint requiring a qualifying response in multiple weeks, because incomplete weekly observations can affect whether a participant meets the response definition. The record does not say how such observations were classified or whether imputation was used.

The sponsor’s analysis is labeled non-inferiority, but the non-inferiority margin and the full analysis specification are not reported. Without the margin, the reported p-value cannot be mapped to a clearly stated acceptable difference. The record also does not report the original sample-size assumptions, any multiplicity strategy, interim analyses, or detailed randomization and masking procedures.

The posted information includes one primary outcome and no secondary outcomes. It therefore cannot characterize a wider set of clinical outcomes or provide an account of outcomes that were not posted. The safety summary provides serious adverse-event counts and selected terms, but detailed event-level context and safety-analysis methods are not reported in the registry record. These limitations call for a bounded reading of the results: the posted figures describe the recorded primary responder outcome and safety counts, while several details required to independently reproduce or fully contextualize the analysis are absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Safety and Efficacy Evaluation of BLI400 Laxative in Constipated Adults — NCT02481947.
• Registry record last updated 2020-07-27; status last verified 2020-07.
• Results first posted 2020-06-25.
• 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

NCT02481947 is a completed Phase 3 randomized, double-masked, parallel-group trial sponsored by Braintree Laboratories. It enrolled 459 adults with chronic idiopathic constipation and compared BLI400 Laxative, described as 21 gm BLI400 powder, with lubiprostone, described as a 24 mcg capsule bid.

The primary outcome was CSBM response over 12 weeks, reported in the per-protocol population. The registry lists 47 responders among 187 participants receiving BLI400 Laxative and 56 among 199 receiving lubiprostone. The sponsor reports a Chi-squared non-inferiority analysis with p = 0.016. A simple unadjusted recalculation gives a risk difference of 0.030, with a confidence interval from -0.058 to 0.118 and p = 0.504; the sponsor’s own analysis takes precedence.

The non-inferiority margin, detailed participant flow, and missing-data handling are not reported in the registry record. Serious adverse events affected 2 of 225 participants at risk in the BLI400 Laxative group and 1 of 229 in the lubiprostone group; deaths were reported as 1 and 0, respectively.