Treatment of Hyperphagia Behavioral Symptoms in Children and Adults Diagnosed With Prader-Willi Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Hyperphagia Behavioral Symptoms in Children and Adults Diagnosed With Prader-Willi Syndrome (NCT01968187), a randomized phase 2 study. The primary outcome is Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group phase 2 study of intranasal carbetocin (FE 992097) versus placebo in children and adults with Prader-Willi syndrome. The registry describes the condition of interest as hyperphagia in Prader-Willi syndrome and records enrollment of 38. The study status is completed. The start date was 2014-01-20, and primary completion was 2014-07-16.

The primary outcome was change from baseline in the HPWSQ-R total score at the end of treatment, defined for this measure as Day 15. The registry also lists four secondary outcomes: the Clinical Global Impression-Improvement score, HPWSQ-R domain scores, the Children's Yale-Brown Obsessive Compulsive Scale score, and the Reiss Profile food-domain score. These outcomes were also assessed at the end of treatment. The listed outcome timeframes and descriptions do not establish what happened at every visit or how missing assessments were handled.

The primary analysis population was the full analysis set. The registry describes this as all participants in the safety population who had the primary efficacy endpoint measured at baseline and at the phone call around Day 8 or at Day 15; analyses were conducted according to randomized treatment. The reported primary group counts are 17 for carbetocin and 20 for placebo. The reason that these counts differ from the enrollment count is not reported in the registry record.

Randomization, double masking, and parallel groups describe the broad design, but they do not reveal the sequence-generation method, allocation concealment, treatment duration details beyond the stated endpoint timeframe, or masking procedures. The protocol and the trial's original sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: In total, 38 subjects were screened and randomized. One subject in the Carbetocin (FE 992097) arm was randomized in error and did not receive the investigational medicinal product (IMP), and was listed as a screening failure. Of the randomized subjects, 37 subjects were exposed to IMP: 17 to Carbetocin (FE 992097) and 20 to placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population included the full analysis set (FAS) which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call \[Day 8\] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The analysis population included the safety analysis set (SAS) which consisted of all subjects who received any amount of the IMP. Analyses for the safety population were conducted according to the actual treatment received.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15), measured over From Day 1 (baseline) to Day 15.

The primary endpoint was change from baseline in the total score on the Hyperphagia in Prader-Willi Syndrome Questionnaires-Responsiveness (HPWSQ-R) at Day 15. The registry describes this as an 11-item questionnaire completed by a parent or caregiver using a one-week recall period. Items cover behavior, drive, and severity, and are rated on a five-point scale. The total is the sum of all items; its range is 11, indicating no hyperphagia behaviors, to 55, indicating the most severe hyperphagia behaviors.

Change in a repeated score can capture whether the measured behaviors shifted during the treatment period, while comparing the groups can distinguish a common change over time from a difference associated with randomized assignment. Because lower scale scores correspond to fewer or less severe behaviors, a more negative change indicates a larger reduction in the measured score. This is a statistical interpretation of the scale direction, not a clinical judgment about what size of change matters to participants.

The endpoint is based on a caregiver-reported measure rather than a direct count of events. Its meaning therefore depends on the questionnaire, recall period, and completeness of assessments. The registry record does not report a threshold for a clinically important change, nor does it establish how the observed score changes relate to longer-term outcomes.

7. Results Posted in the Registry

• Carbetocin (FE 992097): mean -15.60 versus -8.90 on control; difference -6.70 (95% CI -14.58 to 1.18), standardized effect d = -0.55; z-test p = 0.096.

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.

Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (Day 15)

• 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:
  • Carbetocin (FE 992097): mean 2.70 versus 3.60 on control; difference -0.90 (95% CI -2.18 to 0.38), standardized effect d = -0.47; z-test p = 0.167.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Carbetocin (FE 992097) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (Day 15)

• 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:
  • Carbetocin (FE 992097): mean -8.80 versus -2.60 on control; difference -6.20 (95% CI -11.93 to -0.47), standardized effect d = -0.73; z-test p = 0.034.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Carbetocin (FE 992097) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (Day 15)

• 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:
  • Carbetocin (FE 992097): mean -6.90 versus -2.50 on control; difference -4.40 (95% CI -9.27 to 0.47), standardized effect d = -0.61; z-test p = 0.076.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Carbetocin (FE 992097) and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists four secondary measures covering global improvement, HPWSQ-R domains, obsessive-compulsive symptoms, and the food domain of the Reiss Profile. Across the posted comparisons, the group contrasts generally point in the same direction as the primary endpoint: the carbetocin group has larger decreases or lower scores on measures where lower values represent less symptom burden. The registry's sponsor analyses report nominal evidence of between-group differences on the listed secondary outcomes, while the unadjusted recalculations do not all reach the same inferential conclusion.

This pattern can add context to the primary result because the measures address related but distinct aspects of behavior and symptom assessment. It does not independently establish the primary result, and the outcomes are not interchangeable. A global rating, a domain score, and a specific symptom scale may differ in measurement properties, recall, and interpretation. The registry record does not report thresholds for clinically important change on these secondary measures.

Multiple outcomes create a multiplicity concern: when many comparisons are made, the chance of at least one apparently notable result can rise even if no underlying differences exist. The registry record does not report a multiplicity adjustment or a hierarchy controlling how secondary outcomes were tested. The secondary findings should therefore be treated as exploratory or supportive rather than as independent confirmation, particularly when their p values are unadjusted or when the analysis details are incomplete.

Because the sponsor's adjusted results and the unadjusted recalculations do not always align, interpretation should distinguish the posted sponsor analyses from the simple recalculations. The broader directional pattern is descriptive; it does not remove uncertainty about the primary endpoint or establish effects beyond the measured outcomes and timeframes.

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

• Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (Day 15)
• Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15)
• Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (Day 15)
• Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (Day 15)

9. Statistical Interpretation

10. Statistical Methods Explained

For a continuous outcome, a group mean summarizes the average measured score or change for participants in that group. The posted primary results are least-squares means, which are model-based averages rather than necessarily simple arithmetic means. The registry identifies ANCOVA as the sponsor's reported comparison method. In general, analysis of covariance compares groups while adjusting for selected covariates, often including a baseline value. The covariates actually used in this trial are not reported in the registry record, so the specific adjustment cannot be reconstructed from the posted information.

What does the standard error describe?

A standard error describes the uncertainty in an estimated mean, rather than the spread of individual participants' scores. Smaller standard errors generally indicate more precise estimates of group means. The registry reports standard errors of 3.06 for the carbetocin group and 2.61 for placebo on the primary endpoint. These values do not show the full distribution of individual changes. In particular, the standard error should not be read as a standard deviation of participant outcomes.

The unadjusted comparison is recalculated from the posted group summaries. It estimates the difference between the group changes and uses an approximate pooled standard deviation derived from those summaries. This is a simple, unadjusted calculation; it does not include the ANCOVA adjustment or any unreported model features. The recalculated estimate is -6.7, matching the sponsor's reported point estimate, but the uncertainty and p value differ. Matching point estimates do not imply that the methods or inferential results are equivalent.

How should the confidence interval be read?

A confidence interval describes a range of values compatible with the data and the statistical method used, under the method's assumptions. It is not a range containing a fixed proportion of individual participants' outcomes, and it does not assign a probability to a particular treatment effect after the data are observed. The recalculated primary interval, -14.58 to 1.183, crosses zero. That means the unadjusted estimate does not distinguish a negative contrast from no difference or a positive contrast at the level represented by that interval. The sponsor reports a 90% interval but only its upper bound, -2.2; the missing lower bound prevents a complete reading of that interval.

A p value measures how surprising data at least as inconsistent with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The primary unadjusted p value is 0.096, whereas the sponsor's ANCOVA p value is 0.029. The discrepancy means that the conclusion depends on the analysis method, and the registry does not provide enough detail to reproduce the sponsor's model.

Why can adjusted and unadjusted results differ?

Adjustment can change the estimated uncertainty and can change the estimate when the model accounts for baseline values or other variables related to the outcome. It may improve precision when the model is appropriate, but its result depends on which covariates and assumptions are used. Those details are not reported in the registry record. The unadjusted recalculation is therefore best understood as a check based on the available group summaries, while the sponsor's ANCOVA is the registry's reported primary analysis and takes precedence when the results conflict.

The reported primary population is the full analysis set, defined by safety-population membership and measurement of the endpoint at baseline and at the phone call around Day 8 or at Day 15. The registry says participants were analyzed according to randomized treatment. This identifies the broad analysis set and assignment principle, but does not report the handling of intermittent missing values, the method for deriving the Day 15 result when a Day 8 assessment was available, or any imputation procedure. The analysis should not be assumed to include every randomized participant merely because the study was randomized.

Why does over-dispersion matter in general?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model expects. If it is ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. It is most relevant to outcomes whose variance is modeled in relation to their mean, such as counts. The posted primary endpoint is continuous, and no over-dispersion assessment or correction is reported in the registry record; there is no basis to claim that it affected this analysis.

Several analysis details that would help evaluate reproducibility are not reported in the registry record, including the full statistical analysis plan, ANCOVA covariates, missing-data method, and any interim analyses. Those omissions do not invalidate the posted results, but they limit the ability to independently reconstruct the sponsor's analysis or determine how all planned analyses were selected and interpreted.

11. Confidence Intervals and Precision

Precision concerns how narrowly an estimate is determined by the observed data and the analysis method. The unadjusted primary contrast is -6.7, with a confidence interval from -14.58 to 1.183. Because this interval includes zero and extends across both negative and positive values, the posted summary statistics leave substantial uncertainty about the size and direction of the unadjusted contrast. The interval is not evidence that every value within it is equally plausible, nor does it describe individual participant responses.

The sponsor's ANCOVA result reports a 90% confidence interval upper bound of -2.2, but the lower bound is not reported in the registry record. Without both bounds, the full interval's width and lower endpoint cannot be assessed. The sponsor also reports p = 0.029. That p value and the reported interval should be attributed to the sponsor's adjusted analysis, not combined with the interval from the unadjusted recalculation.

Group standard errors are 3.06 for carbetocin and 2.61 for placebo. They quantify uncertainty in the group mean estimates, not the variability of individual outcomes and not the uncertainty of the group difference by themselves. The trial's relatively small reported endpoint groups mean that estimates should be read with attention to their uncertainty; no additional precision estimate should be inferred from enrollment alone.

Precision also depends on the model and analysis population. Since the ANCOVA details and lower confidence bound are not reported, the sponsor estimate cannot be fully checked from the registry record. The unadjusted interval is reproducible from the posted summary statistics but answers a narrower question than the sponsor's adjusted comparison.

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 illustrative, not the trial's original design calculation. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The figures are participants per arm, not total participants or total events, because this is a continuous outcome. The original sample-size assumptions and justification are not reported in the registry record.

For each assumed effect size, the 80% power column gives the estimated number of participants per arm under which a study would have an 80% chance of detecting an effect of that size at the stated significance level, if the planning assumptions hold. The 90% column applies the same idea with a higher chance of detecting the specified effect. These are design-planning quantities; they are not probabilities that the observed result is true, and they are not evidence about the actual chance this completed study had to find a result.

The displayed scenarios scale the effect to be detected relative to the observed effect: 100%, 75%, and 50%. As the effect to detect becomes smaller, more participants are needed to distinguish it from random variation under the same assumptions. For example, the primary outcome's planning illustration lists 52 participants per arm for 80% power when planning for 100% of the observed effect, and 206 participants per arm when planning for 50% of the observed effect. The corresponding 90% figures are 69 and 275.

These calculations are planning illustrations based on the observed effect, not the study's original design parameters. They do not show observed power and should not be used to reinterpret the trial outcome as if a post hoc power calculation could resolve the uncertainty. They also do not account for any features not included in the stated assumptions, such as a different allocation, an adjustment model, or missing outcome data.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -6.700; pooled standard deviation σ = 12.113.
2. n = 2 × (1.96 + 0.842)² × 12.113² / -6.700² = 51.3, rounded up to 52 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
delta <- -6.7                      # observed difference in means
sigma <- 12.1131536533048                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1968187)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 52 (80% power), 69 (90% power)
 75% of observed effect: n per arm = 92 (80% power), 123 (90% power)
 50% of observed effect: n per arm = 206 (80% power), 275 (90% power)
power.t.test: 52.3 
Simulated power at n = 52 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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. Analyses Reported by the Sponsor

The registry reports the sponsor's primary comparison as an ANCOVA least-squares mean difference of -6.7, with a reported 90% confidence interval upper bound of -2.2 and p = 0.029. The lower confidence bound is not reported. The unadjusted recalculation based on the group summaries also estimates a difference of -6.7, but gives a confidence interval from -14.58 to 1.183 and an unadjusted p value of 0.096. Thus the point estimate agrees while the uncertainty and statistical conclusion differ.

ANCOVA and the recalculation are not interchangeable. The sponsor's model may account for baseline or other covariates, but the covariates and full model specification are not reported in the registry record. The recalculation uses the posted summaries without adjustment and cannot reconstruct the sponsor's model. Because the discrepancy flag is true, the sponsor's own analysis takes precedence. The recalculation remains useful as a transparent sensitivity check on the summary data, but it should not be presented as the primary sponsor result.

The registry also reports sponsor ANCOVA analyses for secondary outcomes. Their model details and complete confidence intervals are not reported, so the same caution applies when comparing those adjusted results with unadjusted calculations from group summaries.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes, with multiple analyses posted. When more than one statistical test is conducted, the chance of at least one result appearing statistically notable can increase. General statistical practice may address this through a prespecified testing hierarchy, adjustment of significance thresholds, or a distinction between confirmatory and exploratory analyses. Which approach, if any, was planned for this trial is not reported in the registry record.

The sponsor's reported secondary-outcome p values should therefore be read as nominal results unless the registry identifies a multiplicity procedure; it does not. The posted unadjusted recalculations also do not correct for testing multiple outcomes. Neither set of results should be treated as if it were protected from multiplicity by a method that is not documented.

The registry defines the primary full analysis set as participants in the safety population who had the endpoint measured at baseline and at the phone call around Day 8 or at Day 15, analyzed according to randomized treatment. This provides some information about analysis population membership. However, the reasons for missing measurements, the number of participants with each assessment, and the methods used to handle missing data are not reported in the registry record. There is no basis to assume that missing values were absent or handled in a particular way.

Further details that would aid interpretation are also not reported in the registry record: the complete statistical analysis plan, the prespecified covariates in the ANCOVA, any interim analyses, and the original sample-size justification. Their absence limits assessment of whether the analyses followed a prespecified plan and how the sponsor addressed multiple testing or incomplete follow-up. These gaps are important for interpretation but do not establish that any particular method was or was not used.

16. 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 non-serious adverse event terms

The registry reports zero serious adverse events affecting participants in the carbetocin group, with 17 at risk, and zero in the placebo group, with 20 at risk. It also reports zero deaths in either group. No serious adverse-event terms are listed. These are counts during the trial's reported safety observation period, not proof that serious events cannot occur.

Other adverse events affected 7 of 17 participants in the carbetocin group and 8 of 20 in the placebo group. These figures are separate from the serious adverse-event counts and should not be conflated with them. The registry record does not provide further detail on event types, severity, duration, or attribution.

With relatively small reported safety groups and an endpoint at Day 15, the absence of recorded serious events gives limited information about uncommon events or longer-term safety. These counts describe what was recorded in this study; they cannot establish comparative safety beyond the trial's participants and observation period.

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

The primary outcome measures caregiver-reported hyperphagia-related behaviors on the HPWSQ-R over the interval from baseline to Day 15. The posted group means show decreases in both groups, with a larger decrease in the carbetocin group. The sponsor's ANCOVA reports a between-group difference and a p value of 0.029, while the unadjusted recalculation gives a confidence interval that includes zero and an unadjusted p value of 0.096. The sponsor's analysis takes precedence when these results conflict, but the discrepancy and incomplete reporting of the adjusted interval warrant careful reading.

These results do not establish the size of a clinically important benefit. The registry record does not report a clinically meaningful threshold for the HPWSQ-R, and the score change cannot by itself determine how participants or caregivers experienced the difference. It also does not show whether changes persisted beyond Day 15, whether they affected other outcomes not measured, or how results varied across subgroups.

The secondary outcomes provide additional measures, but multiple testing and incomplete analysis details mean they should not be treated as independent confirmation. The safety counts describe recorded events in a limited study group and follow-up period; zero serious events does not prove zero risk.

In general, a trial result is an estimate subject to uncertainty, measurement limitations, and the assumptions of its analysis. The registry record describes a randomized comparison but does not include enough statistical detail to reproduce the sponsor's adjusted model. The findings should therefore be understood as results for the measured questionnaire outcomes and stated timeframe, rather than a complete account of long-term outcomes or effects in every person with Prader-Willi syndrome.

18. Why This Trial Matters Statistically

This trial illustrates why a reported treatment contrast should be read together with its analysis method and uncertainty. The sponsor's primary ANCOVA and the unadjusted recalculation produce the same point estimate but different inferential conclusions. That distinction is not a technical footnote: it affects how strongly the observed contrast can be separated from uncertainty using the available summaries. Reporting the analysis model and complete interval is essential for readers trying to understand or reproduce the result.

The study also illustrates the importance of separating an outcome's direction from its clinical meaning. The HPWSQ-R has a defined score range and direction, making it possible to interpret lower changes as reductions in the measured behaviors. But a score difference does not automatically identify a clinically important change, and no such threshold is reported in the registry record.

Planning calculations based on observed effects can show how estimates of required group size vary when the target effect changes. They are not the original design justification and do not convert a completed trial's result into observed power. This distinction is especially relevant when a study has small reported endpoint groups and uncertainty around the primary contrast.

Finally, a set of secondary outcomes can broaden the description of a study while also increasing multiplicity. Without a reported plan for interpreting multiple tests, a pattern of nominal findings should be treated cautiously. These are general lessons in reading clinical trial statistics, illustrated by the design and reporting details of this study.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves important analysis details unspecified. Although the sponsor reports ANCOVA, the covariates, model specification, and complete primary confidence interval are not reported. The unadjusted recalculation therefore cannot reproduce the sponsor analysis, and the reported difference in inferential conclusions cannot be resolved from the posted summaries alone.

The primary analysis population has a registry definition, but missing-data handling is not described. The reason the endpoint group counts differ from enrollment is not reported in the registry record. The record also does not report how many assessments were available at each time point, whether any values were imputed, or how the Day 8 phone assessment related to the Day 15 endpoint analysis.

The primary outcome is a caregiver-completed questionnaire with a one-week recall period. That makes the measure relevant to observed behaviors but dependent on caregiver report and recall. The registry does not report a clinically important threshold for score changes. Follow-up for the primary endpoint ends at Day 15, so longer-term persistence is not established by these results.

The secondary outcomes involve multiple statistical comparisons, but a multiplicity strategy is not reported. The original sample-size assumptions, interim analyses, and full statistical analysis plan are also not reported in the registry record. Finally, the reported safety group counts are limited in size and observation period, which restricts what can be concluded about uncommon or longer-term adverse events.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Treatment of Hyperphagia Behavioral Symptoms in Children and Adults Diagnosed With Prader-Willi Syndrome — NCT01968187.
• Registry record last updated 2025-03-27; status last verified 2025-03.
• Results first posted 2025-03-27.
• 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.

23. Record Summary

NCT01968187 is a completed randomized, double-blind, parallel-group phase 2 trial of intranasal carbetocin (FE 992097) versus placebo in children and adults with Prader-Willi syndrome. The registry records enrollment of 38 and primary completion on 2014-07-16.

The primary endpoint was change from baseline to Day 15 in the caregiver-completed HPWSQ-R total score. The sponsor's ANCOVA reports a least-squares mean difference of -6.7 and p = 0.029, with the lower bound of its 90% confidence interval not reported. An unadjusted recalculation gives the same point estimate but an interval from -14.58 to 1.183 and p = 0.096. Because the posted results differ, the sponsor's analysis takes precedence.

The record lists four secondary outcomes and reports no serious adverse events or deaths in either group. Multiplicity handling, missing-data methods, full ANCOVA details, and the original sample-size justification are not reported in the registry record.