Pharmacokinetics of a Single Treatment Cycle of AA4500 0.58 mg in Men With Peyronie's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of a Single Treatment Cycle of AA4500 0.58 mg in Men With Peyronie's Disease (NCT01430169), a na phase 2 study. The primary outcome is AUX-I Cmax After Injection 1.

2. Clinical Question

The study also aimed to assess safety and the pharmacokinetics of both AUX-I and AUX-II. Plasma sampling was scheduled before and after the injections and at later follow-up visits. The primary endpoint focuses on AUX-I concentration after the first injection rather than on a clinical change in Peyronie's disease. Consequently, the question addressed by the posted endpoint is about drug concentration over a specified sampling interval. It does not directly compare clinical outcomes between treatment strategies.

3. Trial Design

This was a Phase 2, open-label, single-group study sponsored by Endo USA Inc., a Keenova Therapeutics Company. The registry record lists 20 participants with Peyronie's disease, a completed status, and study dates from 2011-09 to primary completion in 2011-11. No random allocation or masking was used; allocation is listed as not applicable and masking as none. With no comparator group, the design is descriptive for the pharmacokinetic and safety assessments rather than a controlled treatment comparison.

The study description states that participants received two injections of AA4500 0.58 mg, 24 hours apart. Participants were admitted to the study unit on Day -1 and remained there until after the pharmacokinetic sample following investigator penile plaque modeling on Day 3. The description also lists return visits on Day 4, Day 8, and Day 29 for pharmacokinetic and safety assessments. These are protocol details in the registry summary; additional operational details are not reported in the registry record.

Pharmacokinetic blood sampling was scheduled before and at multiple time points after each injection on Day 1 and Day 2, as well as on Days 3, 4, 8, and 29. For the primary endpoint, the specified window begins 15 minutes before Injection 1 and continues through 12 hours after that injection, with a further pre-injection sample at 24 hours. The endpoint description calls this the interval from pre-injection to 24 hours after Injection 1.

The record reports a pharmacokinetic population of N=19 and says two subjects were excluded from the analysis for bioanalytical reasons, specifically ELISA interference. It does not explain the apparent relationship between that exclusion count and the reported analysis population. The sample-size justification, detailed statistical plan, and any interim analyses 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) population (N=19). Two subjects were excluded from the analysis due to bioanalytical reasons (ELISA interference)

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 AUX-I Cmax After Injection 1, measured over 15 minutes before Injection 1 (0 hour for Injection 1); 5, 10, 20, and 30 minutes after Injection 1; 1, 2, 4, 8, and 12 hours after Injection 1; 15 minutes before Injection 2 (24 hours after Injection 1).

The primary endpoint is the maximum plasma concentration of AUX-I after Injection 1, reported as a mean continuous measure in ng/mL with standard deviation as the stated measure of dispersion. AUX-I is identified as clostridial type I collagenase. The endpoint description defines the maximum as the highest measured enzyme concentration during the period from 15 minutes before Injection 1 through the sample taken 24 hours after it, using the listed sampling times. Concentrations were determined with a validated enzyme-linked immunosorbent assay, or ELISA.

In general, a maximum concentration endpoint summarizes the peak observed level over a defined sampling window. It can describe the extent of measured systemic exposure during that window, but its value depends on the sampling schedule and the analytical method. It is not itself a measure of clinical improvement, and a maximum concentration alone does not describe how long a concentration remains elevated or the full concentration-time profile.

The registry record does not report the observed AUX-I mean, standard deviation, or individual values for this endpoint. It therefore does not allow the reader to quantify the reported peak concentration or its variability from the record. The study summary says plasma levels for both AUX-I and AUX-II were to be determined, but this primary endpoint is specifically the AUX-I maximum after Injection 1.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

The primary measure is a continuous pharmacokinetic endpoint: the maximum observed AUX-I plasma concentration after Injection 1. It is expressed in ng/mL, and the registry identifies the mean as the summary parameter and standard deviation as the dispersion measure. The observation window runs from 15 minutes before Injection 1 through the sample at 24 hours after Injection 1, with intervening samples at the listed times. The record says concentrations were measured using a validated ELISA.

In general, a continuous outcome can take different numerical values across participants. A mean describes the central level of a set of values, while a standard deviation describes how spread out those values are around their mean. These summaries answer different questions: the mean concerns the average observed level, while the standard deviation concerns variation among measurements. The registry record gives no numerical mean or standard deviation for this primary endpoint, so neither its level nor its observed spread can be described.

How does the sampling schedule matter?

A maximum concentration is the highest measured value within a specified sampling window. In general, it is an observed peak rather than necessarily the exact biological peak: the time of the true peak may fall between scheduled samples. How well the sampling schedule captures a peak depends on when samples are taken relative to the concentration-time course. The study description lists close sampling after each injection and later sampling on subsequent days. The primary endpoint is limited to the interval following Injection 1 and includes the pre-injection sample at 24 hours.

In general, pharmacokinetic measurements describe drug-related concentrations over time. A maximum concentration provides one feature of that profile. It does not, by itself, provide the full course of concentrations, the duration of exposure, or a clinical outcome. Although the study summary says plasma levels for AUX-I and AUX-II were to be determined, the specified primary endpoint is the AUX-I maximum after Injection 1.

What does the analysis population tell the reader?

The registry record reports a pharmacokinetic population of N=19 and says two subjects were excluded from the analysis for bioanalytical reasons, described as ELISA interference. These statements do not reconcile on their face, and the record does not explain the discrepancy. It is not appropriate to infer a different analysis count or determine which observations contributed to the endpoint. The analysis population for each other outcome is also not reported in the registry record.

In general, an analysis population defines which participants or observations contribute to a particular analysis. Exclusions can affect both the number of observations and the interpretation of results, especially when measurement problems are involved. An assay interference exclusion is a concern about the reliability of a laboratory measurement, but the registry record does not give further details about the interference, which samples were affected, or how missing measurements were handled.

What can be inferred from a single-group design?

This study is described as single-group, open-label, and without allocation to a comparator. In general, a single-group pharmacokinetic study can describe concentrations measured under its dosing and sampling conditions. Without a control or comparator group, it cannot estimate a between-group contrast. Open-label status means masking was none according to the registry record; it does not change the assay-based nature of a plasma concentration measurement, but the record does not describe any additional safeguards or analysis procedures.

No statistical plan, sample-size justification, or interim analysis information is reported in the registry record. The generic sample-size planning assumptions associated with other calculations are not a description of this trial's design or a justification for its enrollment. They do not create an observed treatment effect, and no trial-specific planning result is reported in the registry record for this interpretation.

What do uncertainty measures add?

In general, a confidence interval gives a range of values compatible with the observed data under a statistical model and its assumptions. It conveys estimation uncertainty, which is distinct from the participant-to-participant spread described by a standard deviation. Interpreting a confidence interval also depends on the analysis method and data structure. The registry record does not report a confidence interval, a standard error, or a p-value for the primary endpoint. It is therefore not possible to characterize inferential precision or statistical significance for that measure from the posted information.

Similarly, an observed count is descriptive unless its uncertainty and comparison context are specified. The serious adverse event count is reported for one group, with no comparator. The registry record does not report a statistical comparison for safety. A lack of a reported comparison should not be interpreted as evidence of equivalence or as proof of no risk.

How should planning calculations be distinguished from trial results?

In general, sample-size planning calculations explore how many participants might be needed under stated assumptions, such as a target effect, significance level, allocation, and statistical approximation. These are planning illustrations, not observed outcomes and not measures of the power achieved by a completed study. The registry record does not report the trial's own sample-size justification or a trial-specific statistical plan. Any planning illustrations associated with the record should not be treated as evidence that the study was designed to detect a particular AUX-I concentration difference. In addition, this trial has one group rather than two study arms, so assumptions about equal allocation between arms do not describe the design recorded for this study.

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(17)
m   <- c(12.6)
sp  <- c(8.3)
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  17  12.600  8.300  8.333  16.867

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 0 analyses. It does not report a multiplicity adjustment or explain how the different outcomes were prioritized beyond identifying AUX-I Cmax after Injection 1 as the primary outcome. When a study evaluates multiple outcomes or time points, general statistical practice recognizes that repeated testing can raise the chance of at least one apparently notable result by chance. Adjustments or a prespecified hierarchy can address that concern, but neither approach is described in the registry record.

The record specifies a pharmacokinetic population of N=19 and says two subjects were excluded from the analysis because of bioanalytical reasons, specifically ELISA interference. It does not reconcile those statements. The handling of missing or unusable measurements, the analysis population for each outcome, and any methods for incomplete observations are not reported in the registry record. The study description lists multiple planned sampling times, but does not say whether every planned sample was obtained or how unavailable samples were treated.

The record does not report a statistical analysis plan, interim analyses, a sample-size justification, or inferential results for the primary endpoint. Consequently, the reported endpoint definition and safety counts should be read as limited registry information, rather than as a complete account of analysis decisions or missing-data handling.

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 non-serious adverse event terms

For the AA4500 group, the registry reports 20 participants at risk and 0 participants affected by serious adverse events. This is a descriptive count over the period represented in the registry record. It does not establish that serious adverse events are impossible, and without a comparator it does not estimate a relative difference in serious-event risk. The list of top serious-event terms is empty in the record.

The same group is reported as having 20 participants at risk and 20 affected in the other adverse-event category. The record does not provide event terms, severity breakdowns, or further definitions for that category in the registry record. Participants affected is a participant count, not a count of individual events; the number of events per participant is not reported in the registry record. The deaths field is null. A null entry is not a reported zero and should be treated as unreported rather than as confirmation that no deaths occurred.

In general, safety counts describe what was recorded in a particular study population and follow-up context. They do not by themselves establish comparative safety or rule out uncommon events. The registry record does not provide a comparator group, detailed event narratives, or a statistical comparison of safety outcomes.

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

This study is relevant as a registry record of a Phase 2 pharmacokinetic and safety assessment of one AA4500 treatment cycle in men with Peyronie's disease. It specifies two injections 24 hours apart, the sampling schedule, the assay used for AUX-I concentrations, and the primary endpoint: mean maximum AUX-I concentration after Injection 1. These details define the kind of measurement the study was intended to make.

The primary numerical result is not reported in the registry record. There is no posted mean or standard deviation for AUX-I Cmax in the registry record for this interpretation, nor is a confidence interval or p-value reported. The endpoint therefore cannot be quantified or judged for precision from the record. While the summary describes measurement of AUX-I and AUX-II, it does not provide numerical pharmacokinetic results for either in the registry record.

The study also does not compare AA4500 with another intervention or a control condition. Its single-group, open-label structure means the record cannot establish a comparative effect on drug concentration or clinical outcomes. The primary endpoint is a laboratory concentration measure, not a measure of change in Peyronie's disease. It should not be interpreted as evidence of clinical benefit or lack of benefit.

Safety information is similarly limited. The record reports 0 serious adverse events among 20 at risk, as well as 20 affected among 20 at risk in the other adverse-event category. It does not provide the event details needed to characterize the latter category further, and the deaths entry is null rather than a reported count of zero. These entries do not establish comparative safety or the absence of risk.

Overall, the record describes the intended pharmacokinetic question and some safety counts, but it does not report the primary result or a complete statistical analysis. Conclusions should remain within those limits.

14. Why This Trial Matters Statistically

Pharmacokinetic studies address a distinct statistical question from trials that compare clinical outcomes. They characterize measured concentrations over time under a specified dose and sampling schedule. In this study, the primary measure is the maximum AUX-I concentration after Injection 1. Knowing the endpoint definition, sampling window, assay, and analysis population is necessary for understanding what a reported concentration would represent.

The registry record also illustrates why the reported analysis population matters. It lists a pharmacokinetic population of N=19 while stating that two subjects were excluded from the analysis for ELISA interference. Without an explanation, readers cannot reconcile those statements or determine the count contributing to the endpoint. This is a data-reporting limitation, not a basis for assuming an alternative analysis count.

Statistically, the design also sets clear boundaries. There is one open-label group and no comparator. The study can be described in terms of its planned concentration measurements and reported event counts, but it cannot provide a randomized between-group contrast. Nor does a plasma concentration endpoint directly answer a clinical-effect question. Keeping those questions separate helps prevent pharmacokinetic descriptions from being mistaken for evidence about comparative clinical outcomes.

Finally, the primary endpoint's numerical result is not reported in the registry record. That absence prevents assessment of the estimated concentration and its variability, regardless of the detail in the sampling schedule. The record therefore offers useful design and measurement context, while also showing that endpoint definitions alone are not enough for quantitative interpretation.

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 most direct limitation is that the registry record does not report the numerical result for its primary endpoint. The mean AUX-I Cmax, standard deviation, confidence interval, and p-value are not reported in the registry record. Thus, readers cannot assess the endpoint's observed magnitude, variability, or inferential precision.

The reported analysis-population details are not reconciled: the pharmacokinetic population is N=19, while two subjects are said to have been excluded for bioanalytical reasons, specifically ELISA interference. The record does not explain the disposition of those observations, the analysis population for each outcome, or how missing or unusable samples were handled. The number of enrolled participants is 20.

The single-group, open-label design has no comparator and cannot support a randomized comparison. The primary endpoint is a plasma concentration, not a clinical outcome. The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or details of multiplicity handling across the 12 listed outcome measures. Although the summary describes a sampling schedule through later follow-up, the registry entries do not state whether all planned measurements were collected or how departures from the schedule were addressed.

Safety interpretation is constrained by limited detail. The serious adverse event count is reported, but the record does not provide serious-event terms; the other adverse-event category has a count but no event details in the registry record. The deaths entry is null, not a reported zero. Follow-up completeness and further safety definitions are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics of a Single Treatment Cycle of AA4500 0.58 mg in Men With Peyronie's Disease — NCT01430169.
• Registry record last updated 2017-10-05; status last verified 2017-09.
• Results first posted 2015-05-06.
• 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

NCT01430169 is a completed Phase 2, open-label, single-group study of AA4500 0.58 mg in men with Peyronie's disease. The registry reports enrollment of 20 participants and two injections 24 hours apart. The primary endpoint is mean maximum AUX-I plasma concentration after Injection 1, measured using ELISA over the specified sampling window.

The pharmacokinetic population is reported as N=19; the record also says two subjects were excluded due to ELISA interference and does not reconcile those details. The numerical primary endpoint result is not reported in the registry record. For safety, 0 serious adverse events were reported among 20 at risk, and 20 were affected in the other adverse-event category. The deaths entry is null. No comparator group is recorded.