A Study of AA4500 in Men With Peyronie's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of AA4500 in Men With Peyronie's Disease (NCT01243411), a na phase 3 study. The primary outcome is Percentage Change From Baseline in Penile Curvature.

2. Clinical Question

The study asked whether penile curvature changed over time among men receiving AA4500 under the study's treatment and follow-up procedures. It also included secondary measures concerning symptoms, pain in participants with a specified baseline pain score, subject global assessment, satisfaction, plaque consistency, a composite response, and penile length. The record lists these outcome domains but does not give their numerical results.

Because the design had no separate control group, the central question is descriptive: what change was recorded in the enrolled group? A before-and-after measurement can describe change over the study period, but it cannot by itself distinguish a treatment-associated change from changes that could occur for other reasons. The record does not include a treatment-effect comparison with an untreated or alternative-treatment group.

3. Trial Design

This was a Phase 3, open-label, single-group study of AA4500 in men with Peyronie's disease. The registry lists enrollment of 348 participants and a status of completed. It describes the study as planned for approximately 300 subjects. Allocation is listed as not applicable, consistent with the absence of a randomized group assignment, and masking is listed as none. The sponsor is Endo USA Inc., a Keenova Therapeutics Company.

The intervention is identified as AA4500, with the arm description naming collagenase clostridium histolyticum. The official title describes administration twice per treatment cycle for up to four cycles. The study summary says that after each cycle's final injection, the investigator modeled the plaque in an attempt to stretch or elongate it. Further cycles were not to be administered if curvature was reduced to <15° after the first, second, or third cycle, or if the investigator considered additional treatment not clinically indicated. The examples given include adverse events and allergic reaction.

Participants were to be followed for additional safety and efficacy assessments on Days 168 (± 7 days) and 252 (± 7 days), described as nominal weeks 24 and 36. The primary endpoint is specified at baseline and Week 36. The registry lists the efficacy population as modified intent-to-treat, but does not report its size or the precise inclusion rules for that population.

The study dates are listed as a start in 2010-11 and primary completion in 2012-08. The record does not report a separate control group, a randomization procedure, or a masking procedure beyond identifying the study as open-label with no masking. It also does not report the protocol's sample-size justification or the statistical plan in sufficient detail to establish how the primary endpoint was analyzed.

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: Includes all subjects who were enrolled and received at least 1 dose of study drug; subjects who were enrolled but not treated were excluded from the population

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy is based on the modified intent-to-treat (mITT) population.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change From Baseline in Penile Curvature, measured over Baseline and Week 36.

The primary endpoint is percentage change from baseline in penile curvature, measured at baseline and Week 36. Curvature is described as an angle measured in degrees, while the endpoint expresses change as a percentage. The endpoint description specifies the direction of interpretation: a negative value indicates less curvature than at baseline.

A continuous endpoint retains information about the amount of change rather than reducing each participant's outcome to a yes-or-no category. A group mean can describe the average change, while a standard deviation describes the spread of individual observations around that mean. Those quantities answer different questions: the mean concerns the group's average, and the standard deviation concerns variation among participants. Neither one alone establishes how precisely the mean has been estimated; that requires an appropriate measure of uncertainty, such as a confidence interval.

Measuring curvature at baseline and at a later visit allows the study to describe within-participant change over the follow-up period. Week 36 is the stated primary time point, while the study summary also describes safety and efficacy assessments at Days 168 and 252. The record does not report the numerical mean change, standard deviation, confidence interval, or test result for the primary endpoint. Therefore, the direction and precision of the primary result cannot be assessed from the registry record.

The endpoint is clinically interpretable as a measure of curvature change, but the registry record does not state a threshold for a clinically important change. It also does not provide the distribution of baseline curvature or explain how the percentage calculation was implemented for the analysis. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What a mean and standard deviation describe

The primary outcome is continuous and is summarized in the registry record as a mean with standard deviation. In general, a mean is the arithmetic average of participants' measured outcomes. It gives a central summary, but does not show whether individual changes were similar or widely spread. A standard deviation describes the variability of observations around the mean. It is not the uncertainty interval for the mean and should not be interpreted as a range containing every participant's result.

To understand precision in a group estimate, readers generally look for a confidence interval. In general, a confidence interval gives a range of values compatible with the data under the statistical method used. A narrower interval indicates greater precision than a wider interval, all else being equal. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be evaluated from the posted results.

How to read a change score

The endpoint compares penile curvature at baseline with curvature at Week 36 and expresses the change as a percentage. The registry description states that negative values indicate less curvature. The sign convention is important: it gives the direction of the measure, but it does not establish the size of the change or whether a change is important to participants. Those judgments require the observed estimate and a justified interpretation threshold, neither of which is reported in the registry record.

A mean change can summarize the group's average course, while a change score for each participant reflects that individual's before-and-after measurements. In general, change scores may be influenced by measurement variability at both time points, and by the characteristics of the participants included in the analysis. The registry record does not give the details of curvature measurement reliability, the distribution of baseline values, or the exact statistical implementation of the percentage calculation.

Why over-dispersion can matter

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When a model underestimates variability, standard errors can be too small and confidence intervals can be too narrow; tests may then suggest more certainty than the data warrant. This is a general concern when a model's assumptions do not fit the outcome data. The primary outcome is described as a continuous measure summarized by a mean and standard deviation, but the registry record does not report enough analysis detail to determine whether an over-dispersion issue was assessed or relevant to the model used.

What a single-group design can establish

In general, a single-group before-and-after study can describe observed changes over time among participants who received the study intervention. It does not include a contemporaneous comparator to show what would have happened over the same period without the intervention or under another treatment. Changes could reflect multiple influences, including the passage of time, measurement variation, participant expectations in an open-label study, or other care. These are general interpretive considerations, not findings about what occurred in this study.

A randomized concurrent control group can help distinguish treatment effects from other influences because allocation creates a comparison under the same study conditions. This study is listed as single-group, with allocation not applicable and no masking. The registry record therefore does not support a randomized treatment-effect estimate. It also does not report an adjusted comparison or another design feature that would provide a concurrent counterfactual.

Planning illustrations and observed power

Sample-size planning calculations can illustrate how many participants per arm might be needed to detect a specified effect under stated assumptions. Such calculations are design illustrations, not outcomes observed in a trial. They do not show the probability that a treatment works, and they are not a substitute for an estimate with a confidence interval. The planning assumptions associated with this study describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effect sizes expressed as fractions of the observed effect. Those are planning assumptions and do not describe this study's single-group allocation.

The registry record does not report the original protocol's sample-size justification. Any planning calculation based on an observed effect is distinct from the design rationale used before enrollment and cannot establish that the completed study had adequate precision. The record also does not report the primary endpoint's observed effect estimate, so the basis for such a planning illustration cannot be evaluated from these results.

Registry analysis information

The registry lists the efficacy population as modified intent-to-treat, a continuous primary measure, and no analysis records. It does not state the exact modified intent-to-treat definition, the number included in that population, the statistical test or model, covariates, handling of repeated measurements, or the confidence-interval method. It also does not report whether any analysis was adjusted or whether assumptions were checked. These analysis details are not reported in the registry record, so the specific method used to produce a primary estimate cannot be reconstructed.

In general, statistical methods should match the outcome, design, and analysis population. A report should make clear which participants contributed data, how missing measurements were handled, and how uncertainty was estimated. Those details affect how readers interpret estimates and compare results across analyses. Their absence from the registry record means that the primary result's analysis cannot be independently evaluated from the posted information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("AA4500")
n   <- c(238)
m   <- c(-34.4)
sp  <- c(25.21)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  AA4500  238  -34.400  25.210  -37.619  -31.181

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint and several secondary outcome domains, including symptom severity, pain in participants with a baseline pain score of at least 4, global assessment, satisfaction, plaque consistency, a composite response, and penile length. Testing or interpreting multiple outcomes raises a general multiplicity concern: as the number of separate comparisons increases, the chance of observing an apparently notable result by chance can also increase. Statistical plans may address this by identifying a primary outcome, defining an order for secondary tests, or adjusting inference. The registry record does not report a multiplicity strategy or a hierarchy for the secondary outcomes.

The primary endpoint is identified as percentage change from baseline in penile curvature at Week 36. However, the numerical estimate and analysis are not reported, and the registry lists no analysis records. The record therefore does not establish whether the endpoint was tested, whether a confidence interval was calculated, or how any secondary analyses were handled. No conclusions about statistical significance across outcomes can be drawn from the listed outcome names alone.

The registry identifies the modified intent-to-treat population as the basis for efficacy, but the population's size and definition are not reported. The record does not explain whether participants required a baseline and follow-up measurement to be included, or how participants who discontinued treatment or missed a visit were treated in the analysis. Missing-data methods, such as imputation or model-based handling, are not reported in the registry record.

These omissions matter because outcome availability and analysis-population rules can affect a change estimate. If participants with missing follow-up differ from those with observed outcomes, an analysis limited to observed measurements could represent a different group. This is a general concern; the registry record does not state whether that pattern occurred or how missingness was assessed. The record also does not report sensitivity analyses that might show whether conclusions were robust to alternative assumptions about missing outcomes.

12. 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: penile haematoma (0.6%), prostate cancer (0.6%), inguinal hernia (0.3%), tendon rupture (0.3%), deep vein thrombosis (0.3%).

The registry lists 347 participants at risk in the AA4500 group for serious adverse events, with 13 affected participants. These are participant counts, not a comparison against another treatment or an untreated group. The record also lists 347 participants at risk for other adverse events and 297 affected participants. Those categories should be read as separate registry summaries; the record does not explain whether participants with events in one category also appear in another.

The serious adverse event terms listed include penile haematoma and prostate cancer, each reported as 0.6%, and inguinal hernia, tendon rupture, deep vein thrombosis, and acute myocardial infarction, each reported as 0.3%. These percentages are reproduced as registry entries. The record does not provide event counts by term, timing, severity details, or an assessment of causal relationship for these listed terms. The death count is not reported in the registry record.

In general, safety counts describe events observed and recorded during a study; without a suitable comparison, they do not estimate how much risk is attributable to an intervention. Serious adverse event reporting also does not, by itself, establish that every listed event was caused by treatment. The group size, exposure duration, definitions, and follow-up affect interpretation. The registry describes follow-up assessments but does not provide participant-level exposure or event timing sufficient for a rate-based assessment. The counts should therefore be understood as descriptive registry data, not as evidence of a comparative safety difference.

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

The registry record describes a completed, open-label, single-group Phase 3 study of AA4500 in men with Peyronie's disease. Its primary outcome was percentage change from baseline in penile curvature at Week 36, with negative values defined as indicating less curvature. The record does not report the numerical primary result or its uncertainty. As a result, it does not support a description of how much average curvature changed or how precisely that change was estimated.

The single-group design can describe outcomes among participants who received the study intervention, but it cannot by itself establish that an observed change was caused by AA4500. There is no concurrent control group in the registry record, and the study was open-label. General influences such as time, measurement variability, expectations, or other care cannot be separated from the intervention using a single-group before-and-after comparison alone.

The record also does not provide numerical results for the listed secondary outcomes. Without those results, readers cannot assess whether symptom, pain, satisfaction, plaque, or other outcome measures align with the primary endpoint. The absence of analysis records also prevents assessment of statistical testing, uncertainty intervals, and missing-data handling.

The safety entries describe serious and other adverse events recorded among participants at risk. They are useful as descriptive counts, but the design does not provide a comparative safety estimate. The listed serious event percentages do not establish causation, and the record does not report a death count.

These limits do not erase the value of the study's descriptive information: the registry specifies the intended treatment schedule, follow-up points, outcome domains, and safety counts. They do mean that the posted registry information is insufficient to determine the magnitude or precision of the primary outcome, compare treatment effects, or make a causal conclusion. Such conclusions would require results and analysis details not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between describing change and estimating a comparative treatment effect. The primary endpoint is a before-and-after measure, and the study enrolled participants in a single group. Such a design can document what was observed in that group, but cannot provide the same treatment-effect contrast as a randomized comparison with a concurrent control.

The registry makes the endpoint and its direction interpretable: it concerns percentage change in penile curvature, and a negative value denotes less curvature. It also identifies the intended efficacy population as modified intent-to-treat. Yet the numerical endpoint result, analysis population size, and uncertainty estimate are not reported. This highlights why naming an outcome is not enough to evaluate evidence; readers also need the estimate, its precision, and clear information about who contributed data.

The planned treatment course could vary, because further cycles were to stop under specified curvature or clinical-indication conditions. That feature makes the distinction between planned exposure and actual exposure important. The registry does not report how many cycles participants received or how exposure differences were handled analytically. This is relevant to interpreting both efficacy and safety summaries.

The listing of multiple secondary outcomes also illustrates the importance of prespecified analysis priorities. In general, multiple outcomes require clear interpretation rules to avoid overemphasizing isolated findings. The registry record does not report a multiplicity strategy or numerical secondary results, so this aspect cannot be evaluated.

Overall, the study record provides useful design context and descriptive safety counts, while leaving core statistical evidence for the primary endpoint unavailable. It demonstrates that conclusions depend not only on study phase or enrollment, but on design, reported estimates, uncertainty, analysis populations, and transparent handling of missing data.

15. 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 main limitation for interpreting efficacy is that the registry record does not report the primary endpoint's numerical result. Without a mean change, standard deviation, confidence interval, or test result, the magnitude and precision of the stated primary outcome cannot be assessed. The same reporting gap applies to the secondary outcomes, for which outcome names are listed without numerical results.

The single-group, open-label design provides no concurrent control comparison. Any observed within-group change would not, by itself, separate the intervention's contribution from other changes over time. The record does not report randomization or masking, and allocation is listed as not applicable.

The registry identifies a modified intent-to-treat efficacy population but does not report its size or detailed definition. It also does not describe missing-data handling, exclusions from analysis, the number of participants with Week 36 measurements, or sensitivity analyses. These gaps make it difficult to assess how representative an efficacy estimate would be, even if one were available.

The study allowed stopping subsequent cycles under specified circumstances, but the registry does not report the number of cycles received by participants or how that variation was addressed in analysis. The record also does not provide detailed measurement procedures, analysis model specifications, multiplicity handling, or a protocol-based sample-size justification.

For safety, the registry reports affected-participant counts and selected serious-event terms, but not event timing, term-specific counts, exposure-adjusted rates, or causal assessments. It does not report the death count. These are limitations of the registry information available for interpretation; they do not establish that any unreported analysis or event was absent from other study documentation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of AA4500 in Men With Peyronie's Disease — NCT01243411.
• Registry record last updated 2017-10-05; status last verified 2017-09.
• Results first posted 2015-04-15.
• 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.

19. Record Summary

NCT01243411 is a completed Phase 3, open-label, single-group study of AA4500 in men with Peyronie's disease. The registry lists enrollment of 348 participants and describes a planned course of two injections per cycle for up to four cycles, with later cycles subject to stopping conditions. Safety and efficacy follow-up assessments were planned at Days 168 (± 7 days) and 252 (± 7 days).

The primary endpoint was percentage change from baseline in penile curvature at Week 36, with negative values defined as less curvature. Efficacy is described as based on a modified intent-to-treat population. The registry record does not report the primary numerical result, its uncertainty, or analysis records. It lists secondary outcome domains and descriptive adverse event counts, including 13 participants with serious adverse events among 347 at risk. Because there is no separate control group, the study record does not provide a randomized comparative treatment-effect estimate.