This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty (NCT00667446), a non-randomized phase 3 study. The primary outcome is Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00667446 |
| Phase | Phase 3 |
| Condition | Precocious, Leuprolide Acetate, Luteinizing Hormone (LH) |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 72 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AbbVie (prior sponsor, Abbott) |
| Results posted | Yes |
2. Clinical Question
Population
Children with central precocious puberty who entered an extension study of leuprolide acetate. The stated intention-to-treat definition requires at least one study-drug dose and at least one post-baseline measurement of a maintenance-of-suppression variable, and excludes specified early discontinuations related to inadequate suppression during the lead-in study. The record’s population definition ends with “N= the number,” so its full denominator is not reported in the registry record.
Intervention
Leuprolide acetate depot injections at 11.25 mg or 30 mg, administered intramuscularly every 3 months. The arm descriptions specify twelve injections for each regimen.
Comparator
The two dose groups are described in a parallel study, but allocation was non-randomized and there was no masking. These arms are not a like-for-like control comparison. The registry record does not describe a separate untreated or placebo control group.
Primary question
What percentage of participants had suppression of peak-stimulated luteinizing hormone at Day 1 and Months 6, 12, 24, and 36? Suppression was defined as peak-stimulated LH < 4 mIU/mL. Numerical results for this endpoint are not reported in the registry record.
The study’s stated purpose was to assess the safety of leuprolide acetate over a longer period in children with central precocious puberty. The primary endpoint also tracks a laboratory measure related to suppression, while secondary outcomes cover hormone concentrations, physical signs of puberty, growth, and bone-age change. These endpoints describe different aspects of the study and should not be treated as interchangeable.
3. Trial Design
This was a Phase 3, multi-center, open-label extension study with non-randomized allocation and a parallel design. The study evaluated two leuprolide acetate depot formulations: 11.25 mg and 30 mg. Each arm description specifies intramuscular injections every 3 months, with twelve injections described for each formulation. The planned extension period is 36 months.
The registry lists enrollment as 72 and status as completed. Enrollment is not necessarily the denominator for every endpoint: the record defines an intention-to-treat population using post-baseline measurement and early-discontinuation criteria, and the endpoint’s complete denominator is not reported in the registry record. The study start is recorded as 2008-12 and primary completion as 2012-10.
Because allocation was non-randomized, the dose groups may differ in ways that affect outcome comparisons. The open-label design means treatment assignment was not masked. These features limit how directly differences between arms can be attributed to dose. The record does not report a randomized allocation procedure, masking, or a separate control regimen.
The primary outcome was a percentage with suppression of peak-stimulated luteinizing hormone, assessed at Day 1 and Months 6, 12, 24, and 36. The record also lists secondary outcomes concerning estradiol in female participants, testosterone in male participants, stimulated LH by visit, physical signs of puberty, growth rate, and bone-age change relative to chronological-age change. Numerical results for the primary endpoint are not reported in the registry record, and the analysis population’s full size is not stated.
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: At the end of the Treatment Period, participants who completed the study or prematurely discontinued from the study could enter the Safety Follow-Up Period.
Treatment Period (36 Months)
| Stage | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|
| STARTED | 34 | 38 |
| COMPLETED | 11 | 13 |
| NOT COMPLETED | 23 | 25 |
Reasons for not completing this period:
| Reason | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|
| Ready to enter puberty based on age | 13 | 15 |
| Other | 2 | 2 |
| Personal reasons | 2 | 2 |
| Withdrawal by Subject | 0 | 4 |
| Not Adequately Suppressed on Therapy | 3 | 0 |
| Lost to Follow-up | 1 | 0 |
| Protocol Violation | 1 | 1 |
| Therapeutic Failure | 1 | 1 |
Safety Follow-up Period (12 Weeks)
| Stage | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|
| STARTED | 28 | 26 |
| COMPLETED | 28 | 25 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|
| No Longer Needed Treatment | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-treat, defined as patients who received at least 1 dose of study drug with at least 1 post-baseline measurement of any maintenance of suppression variable, \& did not prematurely discontinue in the 1st 30 days due to inadequate suppression at Month 6 of the lead-in study. N= the number of patients with available data at each time point.
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: Participants who received at least 1 dose of study drug in this extension study.
| Characteristic | Unit | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg | Total |
|---|---|---|---|---|
| Participants analysed | 34 | 38 | 72 | |
| Age, Continuous | years | 8.50 (SD 1.71) | 8.45 (SD 1.52) | 8.47 (SD 1.60) |
| Sex: Female, Male: Female | Participants | 32 | 33 | 65 |
| Sex: Female, Male: Male | Participants | 2 | 5 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone, measured over Day 1, Months 6, 12, 24, and 36.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants whose peak-stimulated luteinizing hormone (LH) was below the study’s suppression threshold. Peak-stimulated LH was defined as the maximum concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist stimulation test. Suppression was defined as peak-stimulated LH < 4 mIU/mL. The assessment visits were Day 1 and Months 6, 12, 24, and 36.
This endpoint converts a laboratory measurement into a binary classification: each evaluated participant either met the stated suppression definition or did not. Reporting a percentage can describe how common that classification was in an analysis population at a visit. It does not, on its own, show the distribution of individual LH concentrations or how much values changed within participants.
The registry specifies a rule for some subsequent observations: participants who failed suppression at a previous visit and prematurely discontinued were counted as having failed at future visits as well. The final visit was each participant’s last visit closest to Month 36. These rules affect how the endpoint is assigned over time and how a visit-specific percentage should be interpreted.
The registry record does not report numerical primary-endpoint percentages or their confidence intervals. Therefore, the endpoint’s definition and assessment schedule can be described, but the observed frequency of suppression and its precision cannot be evaluated from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically specific primary measure: the percentage of participants meeting a laboratory threshold for peak-stimulated LH suppression. It gives the threshold, stimulation-test timing, scheduled visits, and a rule for carrying forward failure after certain discontinuations. However, numerical results for this primary endpoint are not reported in the registry record. Without the event counts, denominators, percentages, and confidence intervals, the degree of observed suppression and the precision of those estimates cannot be assessed.
The study’s two dose groups should not be interpreted as randomized comparison arms. Allocation was non-randomized, and the record describes no masking. Any difference between the groups could reflect differences in their participants or other factors, as well as dose. The record does not provide an adjusted comparison or a statistical analysis plan that would show how such differences were handled. A contrast between groups would therefore be descriptive rather than a secure causal estimate.
The record includes safety counts. For the 11.25 mg group, one serious adverse event is listed among 34 participants at risk; for the 30 mg group, zero serious adverse events are listed among 38 participants at risk. The record also lists 31 participants with other adverse events in each group, with 34 and 38 participants at risk, respectively. These counts describe the recorded groups; they do not establish that the groups had comparable risk or follow-up. The listed serious adverse-event term “INTRACRANIAL PRESSURE INCREASED” is accompanied by 2.9%. The record does not identify the timing or provide further context for that term in the registry record for this analysis.
Confidence intervals are useful because they express the uncertainty around an estimated percentage. A narrow interval generally indicates greater precision, while a wide interval indicates less precision. No primary endpoint intervals are reported in the registry record, so neither the size of the uncertainty nor the range of values compatible with the data can be judged.
Overall, the record describes the intended endpoint, visit schedule, study arms, and selected safety counts, but it does not provide numerical primary endpoint findings. The study’s completion status is not itself evidence of a particular endpoint result. Interpretation should remain limited to what the registry reports, without inferring efficacy or making a causal claim from the non-randomized arms.
9. Statistical Methods Explained
What kind of endpoint is this?
General statistical explanation: a binary endpoint classifies each participant into one of two categories. Here, the categories follow the study definition: peak-stimulated LH either meets the suppression threshold or does not. A percentage describes the fraction of the analysis population assigned to the qualifying category. To interpret a percentage fully, readers need both the numerator (participants meeting the definition) and the denominator (participants evaluated). The primary numerical results and denominators are not reported in the registry record.
The measurement itself is a concentration, but the primary outcome is not the mean concentration. It is the percentage crossing a specified threshold. That distinction matters: a group-level percentage cannot show how far above or below the threshold each participant’s value was. Nor does it describe changes in the full distribution of concentrations.
Why report a confidence interval?
General statistical explanation: an observed percentage is an estimate based on the participants included in an analysis. A confidence interval communicates the uncertainty associated with that estimate under the assumptions of the statistical method. It is not a guarantee that the true value lies within the interval, and it does not account automatically for every potential source of bias. The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but the numerical intervals are not reported in the registry record.
When percentages are based on limited observations, their precision may be limited, especially when outcomes are uncommon or nearly universal. A confidence interval helps readers assess that uncertainty rather than treating the observed percentage as exact. In this case, without reported percentages, event counts, and intervals, that assessment is not possible.
How should repeated visits be understood?
The endpoint is assessed at Day 1 and several later visits through Month 36. Visit-specific percentages describe status at particular assessment times; they are not necessarily a summary of a participant’s entire course. The registry states that participants who failed suppression at a previous visit and prematurely discontinued were counted as failures at future visits. This rule makes the later classifications depend partly on earlier results and discontinuation. It should be considered when interpreting any reported follow-up percentage.
The record defines the final visit as the participant’s last visit closest to Month 36. This is not necessarily a single identical visit time for every participant. A result at that final visit could therefore reflect observations taken at different times near the planned endpoint. Numerical final-visit findings are not reported in the registry record.
What does non-randomized allocation imply?
General statistical explanation: randomization is used to balance, on average, measured and unmeasured baseline factors across treatment groups. With non-randomized allocation, that protection is absent. Differences in outcomes may be associated with dose, but they may also reflect differences between the people assigned to each regimen or other factors. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjusted primary comparison or enough detail to assess such an approach.
Open-label status means masking was absent. General explanation: knowledge of treatment assignment can influence behavior, clinical management, reporting, or assessment, depending on the outcome. The primary endpoint is based on a laboratory measure, but the record does not describe any procedures used to minimize assessment bias. This design feature should be considered alongside non-randomized allocation.
What do planning calculations mean?
General statistical explanation: a sample-size calculation estimates how many participants a future study might need under specified assumptions. It is a planning aid, not evidence about the probability that the completed study detected an effect. The planning illustrations associated with this analysis use a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. The calculations are illustrations, not observed power. Their assumptions and values do not substitute for a trial protocol’s design rationale, which is not reported in the registry record.
These concepts help distinguish endpoint definition, uncertainty, design, and planning from observed findings. For this study, the primary endpoint’s numerical results are not reported, so neither its estimated effect nor its precision can be interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint assessed at multiple visits and a range of secondary outcomes. Repeated assessments and multiple outcomes create multiple opportunities to observe results that appear notable by chance. A statistical plan may specify which endpoint is primary, how visits are handled, and whether any adjustment is used to account for multiple testing. The registry record does not report a multiplicity adjustment or a detailed statistical plan, so it is not possible to determine how such issues were addressed.
The primary endpoint definition includes a particular rule for future visits after prior failure and premature discontinuation: those participants were counted as failures at future visits. This is a stated outcome-handling rule, but it does not describe how all missing observations were treated. The registry record does not report a general missing-data method, imputation procedure, sensitivity analysis, or the amount of missing endpoint data.
The stated intention-to-treat population includes patients who received at least one dose and had at least one post-baseline measurement of a maintenance-of-suppression variable, with an exclusion for premature discontinuation in the first 30 days due to inadequate suppression at Month 6 of the lead-in study. The record’s definition is incomplete after “N= the number,” and the full endpoint analysis denominator is not reported in the registry record. Enrollment is listed as 72, but that number should not be assumed to equal the analysis population for every visit or outcome.
The registry reports zero analyses in its analysis listing. Numerical primary endpoint estimates and the associated confidence intervals are not reported in the registry record. Consequently, the effects of missing data, the analysis population at each visit, and any multiplicity handling cannot be evaluated from the reported information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | 1 | 34 | 2.9% |
| Leuprolide Acetate 3M Depot 30 mg | 0 | 38 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | 31 of 34 |
| Leuprolide Acetate 3M Depot 30 mg | 31 of 38 |
Most frequent serious adverse event terms
| Event term | Organ system | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|---|
| INTRACRANIAL PRESSURE INCREASED | Nervous system disorders | 1 of 34 | 0 of 38 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg |
|---|---|---|---|
| INJECTION SITE PAIN | General disorders | 10 of 34 | 9 of 38 |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | 9 of 34 | 5 of 38 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 4 of 34 | 9 of 38 |
| PYREXIA | General disorders | 6 of 34 | 5 of 38 |
| HEADACHE | Nervous system disorders | 5 of 34 | 6 of 38 |
| PHARYNGITIS STREPTOCOCCAL | Infections and infestations | 5 of 34 | 4 of 38 |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | 4 of 34 | 5 of 38 |
| GASTROENTERITIS | Infections and infestations | 4 of 34 | 4 of 38 |
| NASAL CONGESTION | Respiratory, thoracic and mediastinal disorders | 3 of 34 | 5 of 38 |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | 3 of 34 | 3 of 38 |
Serious events with the highest arm-level rate: intracranial pressure increased (2.9%).
The serious adverse-event counts are listed separately by dose group. In the 11.25 mg group, one serious adverse event is recorded among 34 participants at risk; in the 30 mg group, zero are recorded among 38 participants at risk. These are counts within the registry’s stated groups, not a randomized comparison of risk. The record does not provide a statistical comparison or confidence intervals for these counts.
The registry lists “INTRACRANIAL PRESSURE INCREASED” as a serious adverse-event term and gives 2.9%. The registry entries available do not specify additional event-level details, such as timing or participant characteristics, so the term and percentage should be read only as recorded.
For other adverse events, the registry lists 31 affected participants in each group, with 34 and 38 participants at risk in the respective groups. These counts should be kept distinct from the serious-event counts. The record does not define further the scope of the “other” category in the information.
Deaths are not reported in the registry record. The absence of a listed death count is not evidence that no deaths occurred. Differences in group size, follow-up, and non-randomized assignment also mean that these descriptive counts should not be interpreted as proof of comparative safety.
12. What the Result Does, and Does Not, Mean
The record establishes what the study set out to evaluate: safety during an extension study of leuprolide acetate in children with central precocious puberty, alongside a primary laboratory endpoint measuring the percentage meeting a peak-stimulated LH suppression threshold. It also specifies two depot-dose regimens, the planned assessment schedule, the suppression definition, and selected adverse-event counts.
It does not report numerical results for the primary endpoint. Readers therefore cannot determine from the registry record what percentage met the suppression definition at the listed visits, how those estimates varied over time, or how precise they were. The record’s completed status does not fill this gap, and the design details alone cannot establish an outcome.
The safety counts provide limited descriptive information. They do not show whether event risks differed between dose groups, because allocation was non-randomized and the record does not report a comparative analysis. Counts also do not convey event severity beyond the serious-event classification, duration, timing, or potential relationship to treatment unless those details are separately reported.
General statistical explanation: a finding in one group and a different count in another does not by itself establish that treatment caused the difference. Causal interpretation depends on study design, group comparability, measurement, missing data, and the analysis. Here, non-randomized allocation and open-label conduct require particular caution.
The appropriate interpretation is therefore bounded: the registry describes the study question and methods and reports selected safety figures, but it does not provide the primary outcome estimates needed to judge the observed suppression results. No conclusion about treatment benefit or lack of benefit follows from the information reported.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition is essential to interpreting a clinical study. “Suppression” is not left as a general impression: the registry defines it using peak-stimulated LH below a stated threshold and describes how the stimulation measurement was obtained. That operational definition makes the outcome conceptually reproducible, although numerical results are not reported in the registry record.
It also highlights the distinction between a study’s intended question and its reported findings. The extension was designed to evaluate safety over a longer period, while the listed primary endpoint concerns a laboratory suppression classification. The presence of a clearly defined endpoint and assessment schedule does not, by itself, reveal the observed percentage or its uncertainty.
From a design perspective, the study offers a useful example of limits on between-group interpretation when allocation is non-randomized and masking is absent. Dose groups can be described, but a difference between them cannot automatically be attributed to dose. This distinction is important in registry reading: group labels and parallel structure do not make a study a randomized controlled comparison.
The record also shows why denominator and missing-data details matter for repeated binary outcomes. Participants were assessed at multiple visits, and the registry specifies how some previous failures followed by premature discontinuation were classified at future visits. Yet the full analysis denominator and broader missing-data methods are not reported in the registry record. Without those details and numerical findings, readers cannot evaluate precision or robustness.
Finally, selected safety counts need careful framing. They can describe recorded events in the listed groups, but they do not establish comparative safety. Reading the design, endpoint rules, denominators, uncertainty, and reporting gaps together is central to sound statistical interpretation.
14. 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 principal limitation for interpreting outcomes is that numerical results for the primary endpoint are not reported in the registry record. The percentage meeting the suppression definition, its confidence interval, and the visit-specific denominators are unavailable. This prevents assessment of the magnitude and precision of the primary outcome.
The analysis population is not fully specified in the record: the intention-to-treat definition ends with “N= the number.” Although enrollment is listed as 72, enrollment should not be treated as the endpoint denominator. The record also does not report a general missing-data approach, the number of participants assessed at each visit, or sensitivity analyses.
Non-randomized allocation and open-label conduct limit interpretation of comparisons between dose groups. The record does not report a statistical adjustment for baseline differences, a detailed analysis plan, or procedures to address potential assessment bias. The study’s repeated visits and multiple secondary outcomes raise questions about multiplicity, but an adjustment plan is not reported in the registry record.
The adverse-event information is also limited. Serious-event and other-event counts are listed, but the registry entries available do not give a comparative analysis, confidence intervals, or further context for the listed serious-event term. Death counts are not reported in the registry record. These omissions constrain interpretation of safety and prevent claims about relative risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty — NCT00667446.
- Registry record last updated 2014-01-09; status last verified 2014-01.
- Results first posted 2013-12-10.
- 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.
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18. Record Summary
This completed Phase 3 extension study evaluated leuprolide acetate 11.25 mg and 30 mg depot regimens in children with central precocious puberty. It was multi-center, open-label, non-randomized, and parallel, with a planned 36-month extension. The registry lists enrollment as 72.
The primary endpoint was the percentage of participants with peak-stimulated LH suppression, defined as peak-stimulated LH < 4 mIU/mL, assessed at Day 1 and Months 6, 12, 24, and 36. Numerical primary endpoint results and confidence intervals are not reported in the registry record. The intention-to-treat definition is stated, but its full denominator is not.
The registry lists serious and other adverse-event counts by dose group, including one serious event in the 11.25 mg group and zero in the 30 mg group. Because allocation was non-randomized and the record does not provide a comparative analysis, these counts are descriptive and do not establish a difference between regimens.