Study Evaluating MOA-728 Oral for the Treatment of OIBD in Subjects With Chronic Non-Malignant Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating MOA-728 Oral for the Treatment of OIBD in Subjects With Chronic Non-Malignant Pain (NCT00605644), a randomized phase 2 study. The primary outcome is Percentage of Participants Witn Spontaneous Bowel Movements Within 3 Hours of Treatment.

2. Clinical Question

In statistical terms, the central comparison is the observed frequency of this short-window bowel-movement outcome in each dose group versus placebo. The outcome is binary at the participant level: each participant either met the stated condition within the timeframe or did not. The posted comparison estimates express the difference in proportions between each dose group and placebo, alongside relative measures and unadjusted p-values.

The question is narrower than whether bowel function changed over a longer period or whether participants experienced overall improvement. The recorded primary measure concerns an event within 3 hours of treatment. The registry record does not report a primary outcome definition beyond the title, a longer-term primary timeframe, or posted secondary outcomes.

3. Trial Design

The registry record describes a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of oral MOA-728. It is listed as phase 2 and completed. Masking is recorded as triple. These design features indicate that participants were allocated among separate study groups and that the study was intended to compare MOA-728 doses with placebo under masking. Further details about who was masked are not reported in the registry record.

Enrollment is listed as 128. The five recorded groups were placebo and MOA-728 at 150 mg, 300 mg, 450 mg, and 600 mg. The posted outcome counts were 2 participants in the placebo group, 3 in the 150 mg group, 2 in the 300 mg group, 5 in the 450 mg group, and 6 in the 600 mg group. The numbers of participants shown for those outcome groups were 29, 19, 20, 30, and 30, respectively. These group counts describe the posted primary outcome, not necessarily every participant enrolled or every analysis population.

The registry lists the study start as 2008-01 and primary completion as 2008-05. The sponsor is Bausch Health Americas, Inc. The study's stated purpose was to evaluate safety and the dose-response relationship of N-methylnaltrexone bromide in participants with chronic nonmalignant pain and opioid-induced bowel dysfunction, observing spontaneous bowel movements after administration.

The registry record does not report the original allocation ratio, the precise randomization procedure, dose administration schedule, follow-up beyond the primary timeframe, or the rationale for the planned enrollment. It also does not report a protocol-based analysis population or a detailed statistical analysis plan. The trial design can therefore be described from its registry characteristics and posted group results, but not reconstructed in all operational details.

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

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 Percentage of Participants Witn Spontaneous Bowel Movements Within 3 Hours of Treatment, measured over 3 hours.

The primary endpoint is titled “Percentage of Participants Witn Spontaneous Bowel Movements Within 3 Hours of Treatment.” It is recorded as a count of participants, with a timeframe of 3 hours. In practical terms, it classifies participants according to whether they had a spontaneous bowel movement within that interval. The posted results give the number meeting the endpoint in each group, while the comparisons express the observed proportions and their differences.

A short, defined timeframe makes the endpoint a direct measure of whether the specified event occurred soon after treatment. A binary endpoint can be summarized by counting participants with the event and relating that count to the number assessed in the group. Comparing proportions then describes how often the event was observed in the dose groups relative to placebo. This is a general explanation of binary endpoints, not a claim about additional outcome definitions in this trial.

The measure does not, by itself, describe the number of bowel movements over a longer period, changes in symptoms over time, or participants’ overall experience. The registry record does not report a detailed definition of “spontaneous,” how the event was collected or verified, or whether any additional rules governed assessment within the 3-hour window. The title contains a typographical error (“Witn”); the endpoint is otherwise described as spontaneous bowel movements within 3 hours of treatment.

7. Results Posted in the Registry

• 150 mg: 15.8% (3/19) versus 6.9% (2/29) on control; risk difference 8.9 percentage points (95% CI -9.9 to 27.7), risk ratio 2.29 (0.42–12.45); unadjusted two-proportion z-test p = 0.324.
• 300 mg: 10.0% (2/20) versus 6.9% (2/29) on control; risk difference 3.1 percentage points (95% CI -13.0 to 19.2), risk ratio 1.45 (0.22–9.46); unadjusted two-proportion z-test p = 0.697.
• 450 mg: 16.7% (5/30) versus 6.9% (2/29) on control; risk difference 9.8 percentage points (95% CI -6.4 to 26.0), risk ratio 2.42 (0.51–11.48); unadjusted two-proportion z-test p = 0.246.
• 600 mg: 20.0% (6/30) versus 6.9% (2/29) on control; risk difference 13.1 percentage points (95% CI -3.9 to 30.1), risk ratio 2.90 (0.64–13.22); unadjusted two-proportion z-test p = 0.142.

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical summaries help describe a binary outcome such as whether a participant experienced a specified event. The posted primary endpoint counts participants meeting the condition within 3 hours. The comparisons use the placebo group as the reference and report risk differences, risk ratios, odds ratios, intervals, and unadjusted p-values. The registry record does not report the original statistical analysis plan or identify the procedures used to calculate those comparisons.

What does a risk difference describe?

A risk difference subtracts the event proportion in the reference group from the event proportion in the comparison group. It is an absolute measure: it expresses the change in the proportion of participants meeting the endpoint, rather than a relative multiplier. A risk difference of zero corresponds to equal event proportions. In the posted results, the estimates are 0.089 for 150 mg, 0.031 for 300 mg, 0.098 for 450 mg, and 0.131 for 600 mg, each compared with placebo. These are the registry's reported estimates; no new values are calculated.

General interpretation: an absolute measure can be useful because it stays in the same scale as the event proportions. Its meaning depends on the outcome and timeframe being compared. In this study, it concerns participants with a spontaneous bowel movement within 3 hours, not all bowel movements or longer-term bowel function.

How should risk ratios and odds ratios be read?

A risk ratio compares event proportions as a ratio. A value of one represents equal proportions; values above or below one indicate a higher or lower observed proportion in the comparison group relative to the reference group. The reported risk ratios are 2.289 for 150 mg, 1.45 for 300 mg, 2.417 for 450 mg, and 2.9 for 600 mg. The corresponding intervals are 0.421 to 12.45, 0.222 to 9.458, 0.509 to 11.48, and 0.636 to 13.22.

An odds ratio compares odds rather than proportions. Its value of one also represents equal odds, but the odds scale is not the same as the risk scale. The posted odds ratios are 2.531, 1.5, 2.7, and 3.375 for the 150 mg, 300 mg, 450 mg, and 600 mg groups, respectively. Their intervals are 0.381 to 16.81, 0.193 to 11.64, 0.480 to 15.19, and 0.621 to 18.33. Since these intervals include one, the data are compatible with equal odds as well as with differences in either direction. General explanation: ratio measures are often less intuitive than absolute differences, and their intervals should be read alongside the underlying event counts.

What does an interval convey?

A confidence interval describes a range of values compatible with the observed data under the assumptions of the method used. It communicates uncertainty in an estimate; a broad interval indicates less precision than a narrow one. For a risk difference, zero is the value representing no difference; for a ratio measure, one represents no ratio difference. The posted intervals for all four risk differences include zero, while all four sets of ratio intervals include one. The interval confidence level and calculation method are not reported in the registry record, so neither should be assumed from the posted numbers alone.

What does a p-value convey?

The unadjusted p-values for the four dose-versus-placebo comparisons are 0.324, 0.697, 0.246, and 0.142. General explanation: a p-value quantifies how unusual data at least as discrepant as those observed would be under a specified null model and test procedure. It is not the probability that the null hypothesis is true, nor does it quantify the probability that the result will replicate. The test procedure and any threshold specified in the trial plan are not reported in the registry record. Because four dose comparisons are posted, the distinction between unadjusted results and a multiplicity-adjusted analysis matters; no adjustment is described.

Small event counts make the estimates sensitive to the outcome status of individual participants. General explanation: sparse binary data can yield unstable estimates and broad intervals, particularly for relative measures. That general concern is relevant to interpreting these results because the event counts in the five groups range from 2 to 6. It does not identify which method was used or establish that a particular alternative analysis would change the findings.

The posted values are not marked as recalculated, and the discrepancy indicator is false. No sponsor-versus-recalculation conflict is identified in the registry record. The original analytical methods, model adjustments, missing-data handling, and analysis populations are not reported in the registry record. Statistical interpretation should therefore remain tied to the posted unadjusted summaries rather than attributing an undocumented model or procedure to the trial.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. The four risk-difference estimates are accompanied by intervals that extend on both sides of zero: -0.099 to 0.277 for 150 mg, -0.130 to 0.192 for 300 mg, -0.064 to 0.260 for 450 mg, and -0.039 to 0.301 for 600 mg. Because zero represents no difference, each interval is compatible with no difference and with effects in either direction. The interval widths also show that the estimates do not pin down a narrow range of plausible differences.

The relative-effect intervals are broad as well. Each risk-ratio interval includes one: 0.421 to 12.45, 0.222 to 9.458, 0.509 to 11.48, and 0.636 to 13.22. Each odds-ratio interval also includes one: 0.381 to 16.81, 0.193 to 11.64, 0.480 to 15.19, and 0.621 to 18.33. For ratio measures, one represents no relative difference. These ranges allow substantially different interpretations of the underlying relative effect.

General explanation: intervals become more informative when they are narrow and when they exclude the value representing no effect, but their meaning depends on the confidence level and method used. The registry record does not state the interval confidence level or the method used to produce these intervals. It is therefore appropriate to describe their bounds and whether they include the no-difference value, without assigning an undocumented confidence level.

The modest group sizes and small event counts are consistent with the wide uncertainty visible in the posted comparisons. The registry does not report precision targets or a trial-specific sample-size justification. The confidence intervals are not proof that effects are absent; they show that the posted data leave considerable uncertainty about their magnitude.

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 figures are planning illustrations, not observed trial outcomes. They are expressed as participants per arm for 80% power and participants per arm for 90% power. They do not represent total enrollment across all groups or a count of events. The separate rule for time-to-event outcomes, which uses total events, does not apply to this binary participant-count endpoint.

The planning assumptions are a two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The figures are shown for planning for 100%, 75%, and 50% of the observed effect. For example, for the 600 mg comparison, planning for 75% of the observed effect gives 169 participants per arm for 80% power and 225 participants per arm for 90% power. Those are planning illustrations based on the observed estimate, not original design assumptions reported for the trial.

In plain language, the 80% power column describes the planned number per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column gives the corresponding planning target for a higher chance of detection under the same assumptions. Greater power generally calls for more participants per arm. Likewise, planning for a smaller fraction of the observed effect requires more participants, because smaller differences are harder to distinguish from random variation.

These values are not observed power. They do not establish whether the completed study had adequate power for its original question, because the trial's own sample-size assumptions and justification are not reported in the registry record. The illustration is based on the observed effect and should be read as a planning aid rather than as a retrospective verdict on study quality.

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 = 0.069; treatment proportion p₁ = 0.158; average p̄ = 0.113.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4485 = 0.8790.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4440 = 0.3737.
4. n = (0.8790 + 0.3737)² / (0.0889)² = 198.4, rounded up to 199 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 <- 0.0689655172413793                          # control proportion
p1 <- 0.157894736842105                          # 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(605644)
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 = 199 (80% power), 266 (90% power)
 75% of observed effect: n per arm = 323 (80% power), 432 (90% power)
 50% of observed effect: n per arm = 657 (80% power), 879 (90% power)
power.prop.test: 198.4 
Simulated power at n = 199 per arm: 0.808 (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. Multiplicity, Missing Data and Analysis Populations

Four dose groups are compared with placebo for the posted primary outcome. When several comparisons are examined, the chance of at least one apparently unusual result can differ from that for a single comparison. General explanation: multiplicity procedures can control an error rate across a family of tests, but the approach depends on the planned questions and analysis strategy. The registry record does not report whether a multiplicity adjustment was planned or applied. The posted p-values are unadjusted.

The record lists one outcome measure and no secondary outcome analyses. It does not report whether other outcomes were collected but not posted, how the primary outcome was designated in the analysis plan, or whether the dose groups were also assessed through an overall dose-response test. A formal dose trend should not be inferred from the sequence of observed counts alone.

Missing-data handling is not reported in the registry record. The posted group sizes for the outcome are 29, 19, 20, 30, and 30, while the overall enrollment is 128. The record does not explain whether these group sizes reflect the full randomized populations, participants with available endpoint data, or another analysis set. It also does not describe imputation, exclusions, withdrawals, or sensitivity analyses. Therefore, the posted counts cannot be assumed to represent a particular intention-to-treat, per-protocol, or other defined analysis population.

The statistical analysis plan, endpoint analysis method, and any adjustment for baseline characteristics are not reported in the registry record. It is also not reported whether interim analyses took place or whether any pre-specified stopping rules were used. These absences limit assessment of how completely the posted comparisons reflect the trial's planned analyses. They do not establish that any particular procedure was or was not used outside the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: constipation (3.3%), nausea (3.3%), vomiting (3.3%), syncope (3.3%), arteriosclerosis (3.3%).

The registry reports serious adverse events by group, with participants at risk and participants affected. The placebo group had 0 participants with a serious adverse event among 29 at risk; the 150 mg group had 0 among 19; the 300 mg group had 0 among 20; the 450 mg group had 1 among 30; and the 600 mg group had 2 among 30. These are participant counts. They should not be read as counts of every event, since a participant could potentially experience more than one event.

The registry also reports other adverse events in 4 participants in the placebo group, 3 in the 150 mg group, 9 in the 300 mg group, 12 in the 450 mg group, and 6 in the 600 mg group. These counts are distinct from the serious-event counts as presented in the safety record. The serious-event terms listed include Constipation, Nausea, Vomiting, Syncope, and Arteriosclerosis, each recorded as 3.3%. The registry record does not provide group-specific attribution for those listed terms in this summary.

Deaths are not reported in the registry record. The safety figures describe reported events and do not, by themselves, establish that an event was caused by study treatment. Small group sizes also mean that counts should be interpreted descriptively rather than as precise comparisons of safety risk.

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

The posted results establish that the registry recorded participants meeting the primary endpoint within 3 hours in each group, with counts of 2 in placebo, 3 at 150 mg, 2 at 300 mg, 5 at 450 mg, and 6 at 600 mg. The risk-difference estimates versus placebo were positive for all four doses. At the same time, every risk-difference interval includes zero, and the ratio intervals include one. The uncertainty is substantial, so the point estimates alone cannot characterize the true differences precisely.

The results do not establish that any dose produces a reliable difference in the primary outcome. They also do not establish that the groups are equivalent: the intervals are broad enough to include meaningful differences in either direction. The unadjusted p-values are not a substitute for effect estimates and intervals, and the registry does not report the testing plan or multiplicity adjustment.

The outcome concerns a spontaneous bowel movement within 3 hours of treatment. It should not be extended to outcomes not posted, longer-term bowel function, overall symptom change, or other patient experiences. The registry lists no secondary outcome analyses. The record's stated study purpose includes safety and dose-response assessment, but the posted primary outcome comparisons alone do not establish a formal dose-response relationship.

Safety counts are descriptive and should not be treated as proof of causal attribution. The posted serious and other adverse-event counts can inform a reading of what was recorded in these groups, but the small numbers and lack of detail in the registry record limit broader conclusions. Overall, these data characterize a small set of observed events and imprecise comparisons, rather than settling the size or direction of a treatment effect.

16. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early clinical trials: a binary endpoint can be easy to state, yet remain imprecisely estimated when only a few participants experience the event. Here, the primary outcome is clearly tied to an event within 3 hours, and the posted counts make the observed group results interpretable at a basic level. The accompanying intervals show why the point estimates should not be read in isolation.

The comparisons also illustrate why absolute and relative measures answer different questions. A risk difference expresses an absolute change in the event proportion, while risk ratios and odds ratios express relative comparisons. When event counts are small, relative estimates can have wide intervals, as they do in these results. Considering the event counts, absolute effects, relative effects, and uncertainty together gives a more complete statistical reading than relying on any single measure.

The multi-dose design raises a further issue: four dose groups are compared with placebo, but the registry record does not state whether or how multiplicity was addressed. Nor does it report a formal dose-trend analysis. A sequence of counts may be visually suggestive, but formal claims about dose response require a defined analysis and appropriate uncertainty assessment.

Finally, the registry record demonstrates the limits of registry-level reporting. Important details about the planned statistical analysis, missing data, analysis populations, and original sample-size justification are not reported. Those gaps constrain what can be concluded about whether the posted comparisons match the trial's original inferential plan. Transparent interpretation distinguishes the results that are available from analyses and design assumptions that cannot be established from the record.

17. 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. First, the primary endpoint concerns a short timeframe of 3 hours and only one posted outcome measure is listed. The registry record does not report secondary outcome analyses that could show whether the pattern extended to other timeframes or related measures. The endpoint's detailed operational definition and method of ascertainment are also not reported.

Second, the posted primary outcome counts are small in each group, and the resulting intervals are broad. The comparisons therefore provide limited precision about the magnitude of any difference. The registry record does not report the original sample-size justification, target effect, or statistical plan, so the intended precision and design goals cannot be assessed from the posted results.

Third, five groups create multiple possible comparisons. Although the record reports four dose-versus-placebo comparisons and their unadjusted p-values, it does not report a multiplicity procedure or a formal dose-response analysis. The relative-effect estimates are also uncertain, with broad intervals.

Finally, important design and analysis details are not reported in the registry record. These include eligibility criteria beyond the broad population description, allocation procedures, the analysis population, missing-data handling, exclusions, and any interim analyses. The posted safety data do not report deaths, and the record does not give enough detail to attribute individual adverse events to treatment. These limitations constrain interpretation; they do not establish that unreported methods were absent from the full study documentation.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study Evaluating MOA-728 Oral for the Treatment of OIBD in Subjects With Chronic Non-Malignant Pain — NCT00605644.
• Registry record last updated 2020-08-20; status last verified 2020-08.
• Results first posted 2020-08-20.
• 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.

21. Record Summary

NCT00605644 is a completed phase 2, randomized, parallel-group study of oral MOA-728 versus placebo in participants with opioid-induced bowel dysfunction and chronic nonmalignant pain. The registry records 128 enrolled participants and five groups: placebo and MOA-728 at 150 mg, 300 mg, 450 mg, and 600 mg. The primary outcome counts participants with a spontaneous bowel movement within 3 hours of treatment.

Posted event counts were 2, 3, 2, 5, and 6 in the respective groups. All four risk-difference intervals versus placebo include zero, and the relative-effect intervals include one. The estimates are therefore imprecise. Safety reporting includes serious and other adverse-event counts; deaths are not reported in the registry record.

The registry record does not report the original statistical plan, sample-size justification, missing-data methods, or analysis populations. Results should be read as descriptive posted comparisons, with uncertainty and reporting limitations kept in view.