Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty (NCT02452931), a na phase 3 study. The primary outcome is Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months..

2. Clinical Question

In statistical terms, the study’s primary question is about the proportion of participants meeting a laboratory threshold after treatment, not a difference between treatment groups. Without a control group, the result could describe the frequency of suppression in the enrolled study population, but it could not by itself separate treatment effects from other explanations for changes over time. The record lists several additional outcomes, including height velocity, bone age relative to chronological age, height change, and Tanner scores. Those measures broaden the kinds of observations collected, but the registry does not report their results in the information available for interpretation.

3. Trial Design

This was a Phase 3, multicenter, open-label, single-arm study sponsored by Tolmar Inc. The registry lists the condition as central precocious puberty and describes leuprolide acetate 45 mg as the intervention. The assigned intervention was a subcutaneous injection at 6-month intervals across a 12 month study period. Enrollment was 64. The study is marked completed; the recorded start date is 2015-08-31 and the primary completion date is 2018-09-05.

Because there was one treatment group and no masking, the design is not a randomized controlled comparison. The intervention group’s outcomes can be described, but there is no contemporaneous control group in the record against which to estimate a treatment-group difference. This distinction matters: a within-group observation is not equivalent to a causal comparison between treatment strategies. Open-label status also means participants and study personnel were not masked to treatment assignment, which can matter for outcomes involving judgment or participant reporting. The primary endpoint is a laboratory measure, but the record does not detail laboratory procedures beyond the specified stimulation test and timing.

The primary assessment timeframe was 6 months, even though the planned study period was 12 month. The registry names secondary outcomes related to LH suppression, growth, bone age, and Tanner scores. It lists 20 outcome measures and 0 analyses. A detailed protocol, planned statistical analysis, sample-size justification, interim analysis plan, and handling of protocol deviations are not reported in the registry record. The enrollment figure should therefore be read as the number enrolled, not as evidence that a particular statistical precision or power target was achieved.

For the primary endpoint, the defined population is the ITT population, with eligibility, dosing, and post-dose laboratory criteria specified in the registry. That definition is relevant when interpreting who contributes to an endpoint estimate. The record does not report how many participants met each part of this definition or how many had an evaluable six-month result. Nor does it explain whether all enrolled participants were included in each secondary outcome analysis.

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: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.

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 With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months., measured over 6 months.

The primary endpoint is the percentage of participants with suppression of peak-stimulated luteinizing hormone at 6 months. The registry defines suppression as peak-stimulated LH <4 IU/L. Peak-stimulated LH is the maximum LH concentration measured 30 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. This makes the endpoint a binary classification for each participant: the measured value either meets the stated threshold or it does not.

A threshold-based laboratory endpoint can give a clear, clinically interpretable summary of how many participants meet a prespecified biochemical criterion at a particular assessment time. The percentage conveys the frequency of that classification in the analysis population. It does not, on its own, describe the distribution of LH values, how close measurements were to the threshold, or how values changed from baseline. Those details are not reported in the registry record.

The endpoint is assessed at 6 months, while injections are scheduled at 6-month intervals over the 12 month study period. Thus, the primary endpoint addresses the stated six-month assessment, not the complete course of all outcomes across the study period. The registry record does not report the observed percentage, the underlying count, a confidence interval, or a statistical test for this endpoint. It also does not report a comparator threshold or comparative estimand. Consequently, the endpoint definition is clear, but its numerical result and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary endpoint is binary at the participant level: suppression is defined by whether peak-stimulated LH is <4 IU/L. For a binary outcome, a common summary is the number meeting the definition together with the number assessed, often expressed as a percentage. The percentage describes the observed proportion in the analysis population. The registry record gives neither the primary count nor the percentage, so no such estimate can be interpreted from this record.

What would a confidence interval contribute?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, such as a proportion. A narrow interval generally indicates greater precision, while a wide interval indicates less precision. An interval would not correct design limitations or establish causality; it would describe sampling uncertainty under the method used. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.

Why does the single-group design matter?

General statistical explanation: randomization and a concurrent control group can help distinguish differences associated with a treatment strategy from differences that could arise through other pathways. In a single-group study, an observed proportion is a description of participants receiving the intervention, not a randomized contrast. The registry identifies this study as single-group, open-label, and without masking. It does not report a control-group estimate or a comparative effect measure.

How should statistical tests and p-values be read?

General statistical explanation: a hypothesis test evaluates data relative to a specified null hypothesis and analysis plan. A p-value, when reported, is not a measure of effect size or clinical importance. Interpretation depends on the question tested, the model, the assumptions, and whether the analysis was planned. The registry record reports 0 analyses and does not give a primary-endpoint p-value, test, or statistical model. No claim about statistical significance can therefore be made from the registry record.

What do sample-size planning calculations mean?

General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the target effect, variability or event frequency, significance level, power, and design. It is not an observed result and does not show that a study achieved a particular level of power. Any planning illustration associated with the record is described as using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with effects specified as fractions of the observed effect. That setup is not the design of this single-arm study and should not be mistaken for a trial-level randomized comparison or for observed power. The registry record does not report the trial’s own sample-size justification. No planning figure should be treated as an observed endpoint result.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data have, standard errors can be too small and intervals too narrow. Appropriate methods depend on the outcome and design. The registry does not report a model for the primary endpoint, so it is not possible to assess whether over-dispersion was relevant or how it was addressed. For the stated binary endpoint, the record does not specify whether an exact, score-based, or other interval method was intended.

What is the distinction between counts and rates?

For the safety results, the registry reports participants with events and participants at risk. Such counts are descriptive. A rate or comparative risk estimate requires a clearly defined denominator and, for a treatment comparison, an appropriate comparison group. The available record does not provide a control group or event timing details. It would therefore be inappropriate to interpret the safety counts as comparative estimates or to infer causation from them.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Assigned Intervention")
n      <- c(62)
events <- c(54)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Assigned Intervention  62  54  87.1  76.1  94.3  76.6  93.3  76.5  93.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures, including the primary LH suppression endpoint and several secondary outcomes covering growth, bone age, height, and Tanner scores. When multiple outcomes are assessed, the chance of at least one apparently notable finding can increase if many tests are conducted without a plan for controlling multiplicity. General statistical approaches may define one primary endpoint, adjust inference across selected comparisons, or distinguish confirmatory from exploratory outcomes. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or results for those outcomes. It also lists 0 analyses, so there are no reported analysis results from which to assess how multiplicity was handled.

The record defines an ITT population as participants who consented or assented, received at least one dose, fulfilled protocol eligibility criteria, and had at least one post-dose pharmacodynamic laboratory assessment. It does not report the number in that population or clarify how it relates to all 64 enrolled participants. The record also does not report how missing six-month laboratory values were handled, whether any participants discontinued, or whether sensitivity analyses were conducted. These omissions matter because the endpoint percentage depends on who is included and on the treatment of participants without an observed assessment.

Specific plans for interim analyses, imputation, missing-data assumptions, and analysis populations beyond the stated ITT definition are not reported in the registry record. It is therefore not possible to determine whether outcome reporting followed a prespecified statistical plan or how robust a result would be to missingness or alternative analytic choices.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: wheezing (1.6%), rash (1.6%).

The registry reports 1 serious adverse event among 64 participants at risk in the assigned-intervention group. It lists wheezing and rash as serious adverse event terms, each at 1.6%. It also reports 55 participants with other adverse events among 64 at risk, and 0 deaths. These are registry entries describing event occurrence in the single study group; they are not estimates comparing treatment with a control.

A serious adverse event is a classification of seriousness, not by itself a judgment that the intervention caused the event. The counts also do not indicate how long each participant was observed, whether participants experienced more than one event, or whether all events were considered related to treatment. The registry record does not report those details. The two listed serious-event terms should not be assumed to represent distinct participants unless the record explicitly establishes that. The other-event count is likewise a participant count, not a count of all event episodes.

Because there is no concurrent comparison group, the safety figures cannot establish whether event frequency differs from what would have occurred under another treatment strategy. They should be read as descriptive observations from the enrolled group, with the limitations of the reported detail and follow-up information.

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

The registry record establishes that a Phase 3, open-label, single-arm study evaluated leuprolide acetate 45 mg in participants with central precocious puberty. It defines a six-month primary endpoint based on peak-stimulated LH and gives the threshold for suppression. It also records enrollment of 64 participants, the intended injection schedule, selected secondary outcomes, and several safety counts. These details describe the study question and its design.

The record does not report the primary endpoint’s observed percentage or count. It therefore does not show how many participants met the LH suppression definition at 6 months, or how precise such an estimate might be. No confidence interval, p-value, model, or comparative effect estimate is reported. The registry record does not support a conclusion about the magnitude or statistical significance of the primary endpoint result.

The single-group design also limits what could be concluded even if the endpoint percentage were available. A percentage in treated participants is not a randomized comparison with an alternative. It cannot alone establish that any observed outcome was caused by the intervention. Open-label conduct and the absence of a control group are features of the design, not statistical inconveniences that can be removed by reinterpreting a single proportion.

The safety entries should likewise be understood as descriptive. The record reports serious and other adverse event counts, including 0 deaths, but gives no comparative safety analysis. The event counts do not establish causation or quantify a difference from another strategy. Missing information about endpoint denominators, missing-data handling, and analysis methods further limits assessment.

Thus, the available registry information is useful for identifying the study’s structure, defined outcomes, and recorded event counts. It is not sufficient to evaluate the numerical primary efficacy result, its uncertainty, or comparative effects. The distinction between a clearly defined endpoint and a reported endpoint result is essential: the former is present in the record, while the latter is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary endpoint is precisely defined, yet the numerical result needed to evaluate that endpoint is not reported in the registry record. The contrast highlights why endpoint definitions and outcome estimates are different parts of a results record. Knowing the threshold and assessment time explains what was intended to be measured; without the observed count, denominator, and uncertainty, readers cannot assess the reported frequency or precision.

The single-arm design also makes the target of inference important. The study can, in principle, describe outcomes in participants receiving the assigned intervention. It does not include a randomized comparator from which to estimate a treatment contrast. This difference helps prevent overinterpretation of within-group observations as evidence of comparative effects. The open-label design is another feature to consider, particularly for outcomes that may depend on judgment, although the primary outcome is defined through a laboratory threshold.

The record’s definition of the ITT population shows that analysis populations are not always identical to total enrollment. Participants must meet stated conditions, including a post-dose pharmacodynamic assessment. Without the number in that population and the number with an observed six-month result, the denominator for a primary proportion cannot be checked. Missing-data methods are also not reported, making it difficult to evaluate possible sensitivity to incomplete outcome collection.

Finally, the record lists multiple outcome measures but no analyses. This underscores the importance of prespecified statistical methods, multiplicity plans, and complete reporting of estimates with uncertainty. The available information permits a careful description of design and safety counts, while also making clear which statistical conclusions remain unavailable.

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.

Several trial-specific limitations constrain interpretation. First, the registry identifies a single-group study with no allocation to a concurrent control group. The study therefore does not provide a randomized comparison, and a descriptive outcome in the intervention group would not isolate a treatment effect. Second, the study was open-label and masking was listed as none. The registry does not describe procedures intended to reduce potential influence of treatment knowledge on assessment or reporting.

Third, although the primary outcome definition and six-month timeframe are specified, the primary result is not reported in the registry record. There is no observed count, percentage, confidence interval, or statistical test. The number of participants contributing to the primary analysis is also not reported. Enrollment of 64 does not establish that all enrolled participants met the defined ITT criteria or had a six-month measurement.

Fourth, the record does not report missing-data handling, deviations from the intervention schedule, discontinuations, interim analyses, a detailed statistical analysis plan, or a sample-size justification. The listed 20 outcome measures and 0 analyses leave the secondary-outcome findings and approach to multiplicity unavailable for interpretation. The safety information is also limited to the recorded counts and terms, without comparative data or event-level detail. These are limitations of the available registry record; the record does not establish whether additional information exists elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty — NCT02452931.
• Registry record last updated 2020-06-02; status last verified 2020-05.
• Results first posted 2020-05-20.
• 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.

19. Record Summary

NCT02452931 is a completed Phase 3, multicenter, open-label, single-arm study of leuprolide acetate 45 mg in children with central precocious puberty. Enrollment was 64. The assigned intervention was a subcutaneous injection at 6-month intervals during the 12 month study period. The primary endpoint was the percentage of participants with peak-stimulated LH <4 IU/L at 6 months, measured 30 minutes after a GnRHa stimulation test.

The registry record does not report the primary endpoint result, its denominator, a confidence interval, or a statistical test. It lists 20 outcome measures and 0 analyses. The defined ITT population requires at least one dose, protocol eligibility, and at least one post-dose pharmacodynamic assessment, but its size is not reported. Safety entries include 1 serious adverse event among 64 at risk, 55 participants with other adverse events among 64 at risk, and 0 deaths. No control group is recorded, limiting comparative interpretation.