An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation (NCT03120520), a randomized phase 2 study. The primary outcome is Proportion of Overall Responders.

2. Clinical Question

The primary definition required an SBM response during the last 2 weeks of treatment. An SBM responder had more than 3 spontaneous bowel movements (SBMs) per week; an SBM was defined as a bowel movement occurring without laxative use in the preceding 24 hours. Participants with missing primary-outcome information were scored as nonresponders.

This question combines a clinically interpretable event outcome—meeting a prespecified responder definition—with comparisons across three active-dose groups and placebo. The registry reports event counts and group sizes, as well as unadjusted comparisons of each dose with placebo. The interpretation is limited to this responder definition and the stated treatment period: the outcome does not by itself describe the full course of symptoms, the timing of individual bowel movements, or outcomes beyond treatment.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 2 study sponsored by Bausch Health Americas, Inc. The registry lists 124 participants enrolled and identifies CIC as the condition studied. The study is marked completed. The recorded start is 2017-01, and primary completion is recorded as 2018-09-07.

Participants were assigned to one of four groups: matching placebo or plecanatide at 0.5 mg, 1.0 mg, or 1.5 mg. Each regimen was taken orally once daily in the morning for 8 weeks. The registry describes the study as double-blind in its official title, while its design fields list quadruple masking; both descriptions are part of the record. Further details about who was masked are not reported in the registry record.

Random allocation and a parallel-group structure support comparisons between groups assigned to different regimens over the same treatment period. The posted primary outcome covers all randomized participants, with missing primary-outcome data counted as nonresponse. The registry does not report the methods used to generate or conceal the allocation sequence, the exact masking procedures, or whether other analysis populations were specified.

The phase designation is phase 2, and the enrollment is modest in relation to the planning illustrations based on the observed effects. Those illustrations are not the trial’s original design calculations. The trial’s own sample-size justification and design assumptions are not reported in the registry record. The posted results include the primary responder measure and three secondary change-from-baseline measures; analyses for those secondary outcomes are not listed as reported analyses.

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: All randomized participants

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.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Overall Responders, measured over 8 weeks.

The primary endpoint is the proportion of participants classified as overall responders during the 8-week treatment period. The registry defines an overall responder as someone who was an SBM responder for the last 2 weeks of treatment. An SBM responder had more than 3 SBMs per week. An SBM had to occur without laxative use in the preceding 24 hours, and participants missing the outcome were scored as nonresponders.

This binary endpoint reduces a pattern of bowel-movement observations to whether each participant met the stated response rule. That can make the outcome easier to interpret as a group event rate, but it also means that participants just below and well below the threshold are both classified as nonresponders. Likewise, response status does not convey how consistently someone met the threshold over earlier weeks.

As a general statistical point, a binary responder measure can be useful when a study aims to compare the fraction meeting a defined threshold rather than compare average changes on a continuous scale. Its interpretation depends on the operational definition, assessment window, and handling of missing data. Here, the missing-data rule is explicit: missing outcome information was scored as nonresponse. The registry does not report additional detail about the timing or frequency of outcome collection beyond the stated definition and timeframe.

7. Results Posted in the Registry

• Plecanatide 0.5 mg: 32.3% (10/31) versus 22.6% (7/31) on control; risk difference 9.7 percentage points (95% CI -12.4 to 31.8), risk ratio 1.43 (0.62–3.27); unadjusted two-proportion z-test p = 0.393.
• Plecanatide 1.0 mg: 40.0% (12/30) versus 22.6% (7/31) on control; risk difference 17.4 percentage points (95% CI -5.5 to 40.3), risk ratio 1.77 (0.81–3.89); unadjusted two-proportion z-test p = 0.142.
• Plecanatide 1.5 mg: 21.9% (7/32) versus 22.6% (7/31) on control; risk difference -0.7 percentage points (95% CI -21.2 to 19.8), risk ratio 0.97 (0.38–2.44); unadjusted two-proportion z-test p = 0.946.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Plecanatide 0.5 mg: mean 1.09 versus 0.98 on control; difference 0.11 (95% CI -0.47 to 0.69), standardized effect d = 0.09; z-test p = 0.710.
  • Plecanatide 1.0 mg: mean 1.22 versus 0.98 on control; difference 0.24 (95% CI -0.33 to 0.81), standardized effect d = 0.21; z-test p = 0.412.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 0.5 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 1.0 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Plecanatide 0.5 mg: mean 1.97 versus 1.44 on control; difference 0.53 (95% CI -0.40 to 1.46), standardized effect d = 0.28; z-test p = 0.264.
  • Plecanatide 1.0 mg: mean 2.06 versus 1.44 on control; difference 0.62 (95% CI -0.32 to 1.56), standardized effect d = 0.33; z-test p = 0.194.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 0.5 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 1.0 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Plecanatide 0.5 mg: mean 1.71 versus 1.30 on control; difference 0.41 (95% CI -0.55 to 1.37), standardized effect d = 0.21; z-test p = 0.402.
  • Plecanatide 1.0 mg: mean 1.83 versus 1.30 on control; difference 0.53 (95% CI -0.44 to 1.50), standardized effect d = 0.28; z-test p = 0.283.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 0.5 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Plecanatide 1.0 mg and the control. The interval gives the range of effects that remain compatible with the data.

Across the three secondary outcomes, the posted group means generally show positive changes from baseline in both placebo and plecanatide groups. The reconstructed comparisons between the 0.5 mg and 1.0 mg doses and placebo have positive mean-difference estimates, while their intervals include zero. The CSBM summaries also include a higher mean change in the 1.5 mg group than in placebo, but there are no reported comparison analyses for that dose in the posted secondary results. These broad patterns should be read as descriptive, not as a consistent dose-response finding.

The secondary measures provide different views of bowel function: stool consistency, weekly SBM rate, and weekly CSBM rate. They are related to the primary responder endpoint, which depends on meeting an SBM threshold in the final 2 treatment weeks. However, changes in group averages do not directly establish how many participants crossed the responder threshold. A mean change and a binary responder proportion answer different statistical questions.

The secondary estimates and intervals are unadjusted recalculations from posted summaries, and the registry lists no reported analyses for these measures. As a general statistical concern, considering multiple outcomes and several treatment comparisons can make isolated small p-values harder to interpret when no adjustment or hierarchy is specified. The registry does not report such a strategy. For these reasons, secondary results are supportive descriptive context, not a substitute for a prespecified primary analysis.

The record does not provide enough detail to assess the models behind the least-squares means or the handling of missing secondary observations. The standard errors reflect uncertainty in those means, but cannot supply the absent model details. Overall, the secondary outcome pattern does not resolve the uncertainty in the primary responder comparison; rather, it offers complementary summaries with their own limitations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score
• Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM)
• Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant is classified as an overall responder or nonresponder. The group results are therefore event counts among participants assessed under the registry’s rule. The comparison measure is a risk difference, which expresses the active-group event proportion minus the placebo-group event proportion. A positive estimate means the observed proportion was higher in the active group; a negative estimate means it was lower. This measure is on the absolute proportion scale, not a relative percentage change.

What does the confidence interval represent?

As a general statistical explanation, a confidence interval describes uncertainty in an estimate under the assumptions of the method used. A wider interval indicates less precision. For the primary comparisons, each interval includes zero, the value corresponding to no observed difference in proportions. This does not prove that the true difference is zero; rather, the posted estimates do not narrow uncertainty enough to exclude zero at the interval level shown. The record does not identify the method used to construct the primary confidence intervals.

How should the p-values be read?

The posted p-values are explicitly unadjusted. In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions apply. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry record does not state the sponsor’s statistical test or report sponsor analyses. The values should therefore be read as unadjusted comparison statistics rather than as a complete account of the planned inferential analysis.

What do the secondary summaries show?

The secondary outcomes are changes from baseline in weekly average stool consistency on the Bristol Stool Form Scale (BSFS), weekly SBM rate, and weekly complete spontaneous bowel movement (CSBM) rate. The group summaries are least-squares means with standard errors. A standard error describes the estimated uncertainty in a mean; it is not the spread of individual participant measurements. The comparison estimates and intervals for the secondary outcomes are unadjusted recalculations from posted summaries. The registry lists no reported analyses for these outcomes.

For those recalculations, the posted standard errors were used to approximate standard deviations for the comparisons. As a general point, this reconstruction is not the same as reproducing a participant-level analysis: it cannot account for model details, covariate adjustment, repeated-measure structure, or other features not available in the summary data. The registry does not report the analysis model behind the least-squares means, the covariance structure, or the method used to handle missing secondary observations.

Why can variability affect interpretation?

General statistical context: continuous outcomes can vary substantially between participants, and the standard error reflects precision in an estimated group mean rather than individual variability. A mean difference can be small relative to the variability in the data and consequently estimated imprecisely. The reconstructed secondary comparisons rely on approximate variability, so their intervals and p-values should be treated as descriptive calculations, not as a replacement for an unreported sponsor analysis.

The three dose-versus-placebo comparisons for the primary endpoint also raise a general multiplicity issue. When several comparisons are examined, the chance of at least one apparently unusual result can increase if each is judged separately without adjustment. The registry record does not report a multiplicity strategy, a hierarchy among doses, or a single primary contrast. That missing information limits the strength of any reading based on the individual unadjusted p-values.

Finally, the missing-data convention is consequential because a participant with missing primary-outcome information is classified as a nonresponder. This is an explicit part of the endpoint definition, but the registry does not report the amount or reasons for missing outcome data. The available summary does not allow a sensitivity analysis under alternative assumptions. These methods details are important when interpreting the estimates, alongside the counts and confidence intervals.

11. Confidence Intervals and Precision

Precision is limited in the primary comparisons. The risk-difference confidence intervals span both negative and positive values for each plecanatide dose, and each includes zero. For 0.5 mg, the estimate was 0.097 with an interval from -0.124 to 0.318. For 1.0 mg, it was 0.174 with an interval from -0.055 to 0.403. For 1.5 mg, it was -0.007 with an interval from -0.212 to 0.198. The width of these ranges indicates substantial uncertainty about the size and direction of the group differences.

As a general explanation, a confidence interval is a range of values compatible with the data under the interval method and its assumptions. It is not a range containing a known fixed proportion of future results, and it does not assign a probability to the true effect after the data have been observed. A range that includes zero does not establish equivalence; it indicates that the data do not precisely distinguish the estimate from no difference using that interval.

The group sizes for these comparisons were 31.0 in placebo, 31.0 in the 0.5 mg group, 30.0 in the 1.0 mg group, and 32.0 in the 1.5 mg group. The relatively small groups are consistent with broad uncertainty, although the registry record does not provide a formal precision target. The original sample-size assumptions and justification are not reported in the registry record.

The secondary comparisons are also uncertain: their reported unadjusted intervals include zero. They are reconstructed from summary statistics rather than reported sponsor analyses, which adds an important limitation. The estimates can describe the observed pattern, but the intervals should not be mistaken for evidence that differences are absent or for a precise estimate of what might occur in another study.

12. 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 for the binary responder comparisons. They are not totals across groups and are not observed participant counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for each illustration is the stated fraction of the observed effect. The trial’s original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect under those planning assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding number for a higher chance of detection. Neither is a guarantee that a future study will obtain a statistically significant result; power depends on the true effect, variability, analysis, and other design features.

The rows that plan for 100%, 75%, and 50% of the observed effect help show how the assumed effect size changes the planning requirement. Smaller effects need more participants to detect under the same assumptions. In particular, planning around a fraction of an already uncertain observed estimate should be treated cautiously, because the observed effect may not represent the effect in a future study.

These figures are planning illustrations, not observed power. The trial enrolled 124 participants, but that enrollment does not itself establish how likely the study was to detect a particular effect. The displayed planning values do not reconstruct the original protocol’s rationale; they are based on the observed results and the assumptions stated for the illustration.

13. 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 = 0.226; treatment proportion p₁ = 0.323; average p̄ = 0.274.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6309 = 1.2365.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6272 = 0.5278.
4. n = (1.2365 + 0.5278)² / (0.0968)² = 332.4, rounded up to 333 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 <- 0.225806451612903                          # control proportion
p1 <- 0.32258064516129                          # 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(3120520)
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 = 333 (80% power), 445 (90% power)
 75% of observed effect: n per arm = 576 (80% power), 770 (90% power)
 50% of observed effect: n per arm = 1,256 (80% power), 1,681 (90% power)
power.prop.test: 332.4 
Simulated power at n = 333 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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines more than one treatment comparison, outcome, time point, or analysis. In general, if many statistical tests are interpreted individually at the same threshold without adjustment, the chance of at least one result appearing noteworthy by chance can rise. This concern is relevant to a design with three plecanatide doses compared with placebo and multiple secondary outcomes. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a designated dose comparison beyond identifying the primary endpoint.

The primary comparison statistics are unadjusted. The registry does not list sponsor-reported primary analyses, so the posted estimates and p-values do not establish what inferential procedure was planned or used by the sponsor. The secondary outcomes likewise have no reported analyses in the registry. Their comparison values are unadjusted recalculations from summaries and should not be treated as a confirmatory family of tests.

The primary endpoint specifies that participants missing outcome information were scored as nonresponders. This is a clear rule for classification, but the number and reasons for missing primary data are not reported in the registry record. Nor does the record report sensitivity analyses that would show how conclusions might change under other assumptions about missing outcomes. For secondary outcomes, the missing-data approach is also not reported.

The stated primary population is all randomized participants. The registry does not describe other analysis populations, such as a per-protocol population, or explain how exclusions after randomization were handled. Details about the statistical model, covariates, repeated measurements, and treatment of intercurrent events are not reported in the registry record. These omissions do not alter the posted counts, but they limit assessment of whether the reported summaries align with a prespecified analysis and how robust the results are to alternative methods.

Consequently, isolated p-values should not be treated as a complete answer to the study question. The observed effect estimates and confidence intervals are more informative about direction and uncertainty, while still requiring caution because the sponsor’s analysis plan and multiplicity handling are not reported.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group: matching placebo, plecanatide 0.5 mg, plecanatide 1.0 mg, and plecanatide 1.5 mg. The corresponding groups at risk were 31, 31, 30, and 32 participants. No deaths were reported in any group, and no serious adverse-event terms are listed.

Other adverse events affected 4 participants in the placebo group, 7 in the 0.5 mg group, 4 in the 1.0 mg group, and 3 in the 1.5 mg group. These are registry counts; they do not by themselves indicate severity, relatedness, duration, or whether participants experienced more than one event. The registry record does not provide event-level descriptions in the listed serious-event terms.

As a general statistical point, zero reported events in groups of this size should be read as an observation during the recorded study period, not as proof that an event cannot occur. Safety counts are descriptive here, and the record does not report a comparative safety analysis or longer-term follow-up. The listed study regimens lasted 8 weeks.

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

The posted data describe a randomized comparison of three plecanatide doses with matching placebo in adolescents with CIC. For the primary endpoint, the observed number meeting the responder definition was 7.0 of 31.0 with placebo, 10.0 of 31.0 with plecanatide 0.5 mg, 12.0 of 30.0 with 1.0 mg, and 7.0 of 32.0 with 1.5 mg. The comparison estimates are imprecise: all three unadjusted confidence intervals include zero.

This supports a limited conclusion: the registry record shows the observed responder counts and indicates substantial uncertainty about the size and direction of each dose-versus-placebo difference. It does not establish that the doses have the same effect, nor does it establish a reliable benefit or lack of benefit. A nonsignificant p-value is not evidence of equivalence, and the estimates are not precise enough to settle the question.

The endpoint captures whether a participant met a specific SBM threshold during the last 2 treatment weeks. It does not summarize every dimension of CIC, establish durability after treatment, or answer outcomes beyond the 8-week timeframe. The secondary summaries address stool consistency and weekly SBM and CSBM changes, but the registry lists no sponsor-reported analyses for them, and the comparison statistics are unadjusted recalculations from summaries.

The safety record reports no serious adverse events or deaths in the listed groups and records other adverse events by group. These short-term counts are descriptive and do not prove that a treatment is free of risk. They also do not provide a basis for conclusions about uncommon events or longer-term safety.

Overall, the results should be understood as a small phase 2 study’s posted observations, with wide uncertainty and important analysis details absent from the registry record. They are not a recommendation for treatment or a definitive answer about clinical effectiveness.

17. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the gap between observing group differences and estimating them precisely. The responder counts vary across the dose groups, and the point estimates include both positive values and a value close to zero. Yet each confidence interval is wide and includes zero. The estimates therefore communicate more than a binary significant/not-significant label: they show that several materially different effects remain compatible with the observed data.

The study also compares three dose levels with placebo, while reporting a binary primary outcome and several secondary outcomes. That structure raises questions about how comparisons were prioritized and whether multiplicity was addressed. Those details are not reported in the registry record, so the posted unadjusted p-values must be interpreted with restraint. The case demonstrates why a statistical analysis plan matters when several comparisons may be considered.

Missing-data handling is another consequential design feature. For the primary outcome, missing participants were classified as nonresponders. That rule gives a defined endpoint, but the registry does not state how much data were missing or provide sensitivity analyses. A transparent rule is valuable, while missingness information is also needed to understand its influence.

Finally, the planning illustrations demonstrate how sample-size requirements depend on the assumed effect. They use observed effects, which are uncertain in a study with small groups, and should not be confused with the original study’s design rationale or observed power. This distinction is broadly important when translating an exploratory estimate into planning assumptions for future research.

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 limitations specific to this trial affect interpretation. The primary comparisons involve small groups, and the confidence intervals are broad. That leaves uncertainty about the size and direction of the dose-versus-placebo differences. The three active-dose comparisons also create a multiplicity concern, but the registry record does not report how comparisons were prioritized or adjusted.

The outcome is a threshold-based responder measure covering the last 2 treatment weeks. It does not show the full trajectory during treatment, and the response threshold can conceal variation among participants who are all classified as nonresponders. Missing primary outcome information was classified as nonresponse, but the amount and reasons for missingness are not reported. The record does not provide sensitivity analyses for this rule.

The registry posts secondary group summaries but no reported analyses. The comparison results for the secondary measures are unadjusted recalculations from summaries, with approximate variability derived from standard errors. The modeling details behind the least-squares means, handling of missing secondary data, and adjustment for repeated measurements or other covariates are not reported in the registry record.

The trial’s own sample-size justification, original design assumptions, allocation concealment methods, and details about who was masked are also not reported in the registry record. The 8-week regimens and posted event counts do not address outcomes after treatment or provide long-term safety evidence. These limitations constrain conclusions to the short-term outcomes and summaries in the record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation — NCT03120520.
• Registry record last updated 2019-10-04; status last verified 2019-08.
• Results first posted 2019-09-19.
• 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

NCT03120520 is a completed randomized, quadruple-masked, parallel-group phase 2 study of plecanatide in adolescents aged 12 to <18 years with chronic idiopathic constipation. The registry records 124 participants enrolled and an 8-week treatment period. Participants received matching placebo or plecanatide at 0.5 mg, 1.0 mg, or 1.5 mg once daily in the morning.

The primary endpoint was the proportion of overall responders, defined by an SBM response during the last 2 treatment weeks. Posted counts were 7.0 of 31.0 for placebo, 10.0 of 31.0 for 0.5 mg, 12.0 of 30.0 for 1.0 mg, and 7.0 of 32.0 for 1.5 mg. All unadjusted primary confidence intervals include zero. The registry also reports three secondary outcome summaries and descriptive adverse-event counts, but no reported analyses for secondary outcomes. Details of the original statistical plan and sample-size justification are not reported in the registry record.