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 Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration (NCT01161563), a randomized phase 4 study. The primary outcome is Patient Bother From Injection Site Burning and/or Stinging.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01161563 |
| Phase | Phase 4 |
| Condition | Prostate Cancer |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 118 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Watson Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
The trial asked how patients with advanced prostate cancer rated injection-site burning and/or stinging after receiving leuprolide acetate and triptorelin pamoate. The injections were given six months apart, with each treatment administered either six months before or six months after the other. The primary outcome was a patient-reported rating collected approximately 15 minutes after injection.
Population
Patients with advanced prostate cancer. The primary outcome population was per protocol: patients who received both study drugs and completed both post-injection questionnaires.
Intervention
Triptorelin pamoate suspension, injected intramuscularly in the buttock.
Comparator
Leuprolide acetate in a polymeric matrix formulation, injected subcutaneously in the upper or mid-abdominal area.
Primary question
What mean VAS rating of injection-site burning and/or stinging was recorded approximately 15 minutes after each treatment?
The registry describes a randomized crossover trial, so treatment order could differ: leuprolide acetate was administered either 6 months before or 6 months after triptorelin pamoate. The record does not report the method used to generate or conceal the order. It also does not post a direct statistical comparison between the treatment ratings. The posted results therefore describe the mean ratings and their confidence intervals for the per-protocol population, rather than a reported test of the treatment contrast.
3. Trial Design
This was a completed Phase 4 randomized crossover trial in patients with advanced prostate cancer. The registry lists an enrollment of 118. The trial began in 2010-07, and primary completion was recorded in 2011-04. The record identifies Watson Pharmaceuticals as the sponsor.
Participants received both study drugs in different sequences, with injections six months apart. Leuprolide acetate was given subcutaneously in the upper or mid-abdominal area. Triptorelin pamoate was given intramuscularly in the buttock. The treatment descriptions identify the leuprolide acetate formulation as Eligard 45 mg and the triptorelin pamoate suspension as Trelstar 22.5 mg. Because the products, formulations, and injection sites differed together, the trial's treatment contrast does not isolate injection route alone.
Allocation is listed as randomized, and masking is listed as none. The record does not report the randomization procedure, allocation concealment, or further details about how treatment sequence was assigned. It also does not report a protocol description of period effects or any washout interval. The six-month spacing between injections is reported; additional design details are not reported in the registry record.
The primary outcome population was per protocol, defined as patients who received both drugs and completed both post-injection questionnaires. The posted results list 107 participants for each treatment's primary outcome. This is the outcome-specific population reported by the registry, not a statement that all enrolled participants contributed to the primary result. The record does not post an intention-to-treat analysis or explain the difference between enrollment and the per-protocol results.
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
| Stage | Triptorelin First, Then Leuprolide Acetate | Leuprolide Acetate First, Then Triptorelin |
|---|---|---|
| STARTED | 63 | 55 |
| COMPLETED | 58 | 49 |
| NOT COMPLETED | 5 | 6 |
Analysis population for the primary outcome, as defined in the registry: Per-protocol population, defined as all patients who receive both study drugs and complete both post-injection questionnaires.
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.
| Characteristic | Unit | Leuprolide Acetate First, Then Triptorelin | Triptorelin First, Then Leuprolide Acetate | Total |
|---|---|---|---|---|
| Participants analysed | 55 | 63 | 118 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 | 17 | 29 |
| Age, Categorical: >=65 years | Participants | 43 | 46 | 89 |
| Age Continuous | years | 75.0 (SD 9.6) | 73.2 (SD 9.6) | 74 (SD 9.7) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 55 | 63 | 118 |
| Region of Enrollment: United States | participants | 55 | 63 | 118 |
6. Primary Endpoint
The registry lists the primary outcome as Patient Bother From Injection Site Burning and/or Stinging, measured over 15 minutes.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was patient bother from injection-site burning and/or stinging. Responses were collected on a Visual Analog Scale (VAS) with a range of 0-100 mm, approximately 15 minutes after injection. The registry reports the outcome as a mean, with a 95% confidence interval, in units on a scale. The primary population was per protocol: patients who received both study drugs and completed both post-injection questionnaires.
A patient-reported scale is relevant when the outcome of interest is a subjective experience such as immediate injection discomfort. The VAS turns a participant's rating into a numerical measure that can be summarized across participants. A mean describes the average recorded rating, while the confidence interval conveys uncertainty around that estimated mean. Neither measure explains how individual ratings were distributed or whether participants found a particular score important.
The timing matters for interpretation: this measure concerns reported burning and/or stinging approximately 15 minutes after injection. It is not a measure of discomfort at every time after treatment, and it does not summarize other aspects of tolerability. Although the registry lists “Discomfort From Injection” as a secondary outcome, the posted primary endpoint is specifically the VAS measure of burning and/or stinging at the stated assessment time.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For leuprolide acetate, the posted mean VAS rating was 23.87, with a 95% confidence interval from 19.98 to 27.76. For triptorelin pamoate, the posted mean was 5.84, with a 95% confidence interval from 1.95 to 9.73. Each treatment result is reported for 107 participants in the per-protocol population. These are descriptive summaries of the post-injection ratings, not a posted estimate or test of the difference between treatments.
The confidence intervals describe uncertainty around each treatment's mean rating under the analysis represented by the registry result. They are not ranges containing every participant's score, and they do not show the spread of individual responses. The registry does not post a standard deviation or another participant-level dispersion measure for these results. The reported intervals are separate treatment summaries; interpreting them as a formal test of the within-participant contrast would require information about the paired observations and their analysis.
The trial's crossover structure is important. The same per-protocol population received both drugs, with treatment order varying. In a crossover analysis, a direct comparison can use the paired ratings from each participant and account for the fact that ratings from the same person may be related. The registry results do not include that comparative estimate, its uncertainty, or a test statistic. Although the posted mean ratings differ numerically, no new contrast or inferential conclusion should be substituted for the sponsor's analysis. The registry reports no comparative analysis for this continuous endpoint.
The outcome is narrowly timed and specific: it reflects a VAS assessment of burning and/or stinging approximately 15 minutes after injection. It does not establish how participants rated other injection experiences, discomfort at other times, or tolerability in settings beyond this study. The injections also differed in medication, formulation, and route/site, so the observed treatment-level summaries cannot identify which of these features accounts for the ratings.
These results describe the posted per-protocol observations. The record does not provide enough information to assess the influence of missing questionnaires, sequence effects, period effects, or other features of the crossover analysis. No conclusion about a formal treatment difference should be inferred solely from the two means or their separate confidence intervals.
9. Statistical Methods Explained
The registry describes a randomized crossover design and reports a continuous primary endpoint as a mean with a 95% confidence interval. The posted information supports interpretation of the treatment-specific summaries, but it does not show the comparative statistical analysis. No comparative analysis is posted for the continuous endpoint.
What does a mean represent?
A mean is the average of the observed ratings in the analysis population. For this endpoint, the ratings came from a VAS assessing injection-site burning and/or stinging approximately 15 minutes after injection. The mean gives a compact description of the group's central level of reported bother. It does not show whether responses were tightly clustered or varied substantially among participants. The registry does not report a standard deviation or other measure of the distribution of individual ratings.
What does a confidence interval convey?
General explanation: a confidence interval expresses uncertainty in an estimated quantity under the assumptions of the analysis method. A 95% confidence interval is not a range that contains 95% of individual participant scores. It also does not, by itself, establish whether two treatment means differ statistically. In this record, each treatment has its own interval, but a direct comparison requires an estimate and uncertainty for the contrast itself.
For a crossover trial, the paired structure matters. General explanation: when the same participant receives both treatments, an analysis may use the within-participant difference in ratings. The variability of those paired differences depends on how closely a participant's ratings under the treatments are related. Separate treatment means and confidence intervals do not reveal that relationship. The registry record does not report the paired treatment contrast, its confidence interval, or its test result.
Why does treatment order matter?
Participants received the injections six months apart, with either treatment given first. General explanation: crossover analyses may need to consider whether outcomes are affected by treatment order, time period, or effects that carry into a later period. The record does not report whether these issues were assessed or how they were handled. It also does not report the sequence-allocation procedure. The randomized allocation label alone does not describe those analytical details.
How should the per-protocol population be read?
The primary population is defined as patients who received both study drugs and completed both post-injection questionnaires. The registry reports 107 participants for each treatment's primary result. Because the endpoint requires completed questionnaires after both injections, this analysis population is narrower than the enrollment figure. The record does not report participant-level reasons for exclusion or missing questionnaires, and it does not post an intention-to-treat analysis.
What can planning calculations say?
General explanation: sample-size calculations can illustrate the number of participants per arm that might be needed to detect a chosen effect under stated assumptions. Such a calculation is a planning illustration, not observed power and not a description of the trial's original design justification. The stated illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The registry record does not report the trial's own sample-size justification. The planning assumptions do not fill that gap or establish what analysis was prespecified.
Overall, the posted mean ratings and confidence intervals describe each treatment's observed endpoint summary. They do not supply the paired comparison that would directly address the randomized crossover question. The sponsor's own comparative analysis is not posted in the registry record, so no recalculated comparison is presented.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one secondary outcome, “Discomfort From Injection,” and reports two outcome measures. It posts no analyses for the continuous endpoint, and the record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting primary and secondary outcomes. A plan for handling multiple outcomes is therefore not reported in the registry record.
The primary analysis population is per protocol. It includes patients who received both study drugs and completed both post-injection questionnaires. The registry reports 107 participants for the primary result under each treatment. It does not report the number or reasons for missing questionnaires, the treatment sequence of participants without complete data, or how incomplete observations were handled. It also does not report an analysis population based on all randomized participants.
General explanation: missing outcome data can affect a result when the likelihood of having a recorded response is related to the response itself or to treatment experience. A complete-questionnaire per-protocol definition makes clear who is included, but it does not show whether those participants differ from those not included. Without reasons for missingness and details of the analysis, the direction or size of any effect on the estimates cannot be assessed from the registry record.
The crossover design also depends on having ratings after both treatments for the stated per-protocol population. The record does not report whether sensitivity analyses were performed for missing data, whether incomplete pairs contributed to any analysis, or whether sequence and period effects were examined. These details are not reported in the registry record.
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 | 0 | 118 | 0.0% |
| Triptorelin Pamoate | 0 | 118 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Leuprolide Acetate | 0 of 118 |
| Triptorelin Pamoate | 0 of 118 |
The registry lists 118 participants at risk for serious adverse events in each treatment group and records zero serious adverse events for both leuprolide acetate and triptorelin pamoate. It also lists 118 participants at risk for other adverse events in each group and records zero other adverse events for both treatments. No serious adverse event terms are listed.
These figures describe the adverse-event counts entered in the registry for the recorded groups. They do not replace the primary tolerability endpoint, which was the patient-reported VAS rating of burning and/or stinging approximately 15 minutes after injection. A zero count in these categories means that no events were recorded in the corresponding registry fields; it does not establish that no symptoms or experiences occurred outside those categories or were not captured.
Death counts are not reported in the registry record. The record does not provide additional narrative about safety monitoring, event definitions, collection procedures, or how adverse events were attributed when participants received both treatments. Those omissions limit interpretation of the safety entries. The posted counts should therefore be read as registry-reported event summaries, not as a complete account of every possible tolerability outcome.
12. What the Result Does, and Does Not, Mean
The results show that the posted mean VAS rating of injection-site burning and/or stinging was 23.87 after leuprolide acetate and 5.84 after triptorelin pamoate, with the respective 95% confidence intervals of 19.98 to 27.76 and 1.95 to 9.73. These are treatment-specific summaries for the per-protocol population, assessed approximately 15 minutes after injection. They indicate the average ratings recorded at that assessment time, not the experience of every participant.
The results do not provide a formal estimate of the difference between treatments. The registry does not post the paired contrast, its confidence interval, or a test result. The separate confidence intervals cannot substitute for that analysis, particularly because each participant was intended to receive both treatments. The record does not report how the sponsor analyzed the crossover data, and no recalculated comparison is presented.
The endpoint also has a limited scope. It concerns burning and/or stinging soon after injection, not all dimensions of tolerability or later experiences. The trial compared treatment packages that differed in drug, formulation, route, and injection site. The posted summaries do not isolate the contribution of any one of those characteristics.
The per-protocol result applies to patients who received both study drugs and completed both questionnaires. The registry does not explain why other enrolled participants are not represented in this analysis, nor does it post an intention-to-treat result. The findings should therefore be understood as the registry's descriptive results for its stated primary population, with important analytical and missing-data details not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it uses a randomized crossover design for a patient-reported outcome. In general, a crossover can make within-participant comparisons useful because each participant receives each treatment. But the design also means that analysis should reflect paired responses and may need to address order and period effects. The registry presents treatment-specific means and confidence intervals, without the direct comparison that would show how those paired ratings were analyzed.
The endpoint illustrates a distinction between describing group results and estimating a treatment contrast. A mean and its confidence interval summarize one treatment's ratings. A comparative question calls for an estimate of the difference and uncertainty around that estimate, with methods suited to the crossover structure. The record does not report that comparative result. Readers should not treat the two separate summaries as if they were a paired analysis.
The per-protocol definition is another important statistical feature. The primary result includes patients who received both drugs and completed both questionnaires. That definition fits the need for ratings after both injections, but the record does not describe the participants without complete paired assessments or the handling of missing data. This leaves uncertainty about how well the analyzed population represents all randomized participants.
Finally, the study shows why endpoint definition and timing matter. The VAS captures a specific self-reported experience approximately 15 minutes after injection. Its results should not be generalized to other aspects of tolerability or other assessment times. The registry's concise summaries are informative about the stated endpoint, while the lack of a posted crossover comparison limits what can be concluded statistically about the treatment contrast.
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 primary limitation for statistical interpretation is that the registry posts treatment-specific means and 95% confidence intervals but no comparative analysis. It does not report a paired estimate, its uncertainty, or a test result. As a result, the randomized crossover question cannot be answered from the posted summaries alone.
The primary result uses a per-protocol population defined by receipt of both drugs and completion of both questionnaires. Although the record reports 107 participants for each treatment result, it does not explain why the per-protocol population differs from the enrollment figure or provide reasons for missing questionnaires. No intention-to-treat analysis or missing-data sensitivity analysis is reported.
The record does not report whether treatment sequence, period effects, or carryover were assessed, or how these considerations entered the analysis. It also does not report the randomization method or allocation concealment. These omissions matter for evaluating how the crossover design was implemented and analyzed.
The measured endpoint is a subjective VAS rating of burning and/or stinging approximately 15 minutes after injection. It does not describe other dimensions of discomfort or later experiences. In addition, the treatments differed in medication, formulation, route, and injection site, so the comparison cannot isolate the role of route or site from the other treatment differences. The record does not report a sample-size justification, a multiplicity strategy, or further details of the statistical analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration — NCT01161563.
- Registry record last updated 2013-09-06; status last verified 2013-09.
- Results first posted 2013-09-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed Phase 4 randomized crossover trial of leuprolide acetate and triptorelin pamoate in patients with advanced prostate cancer. Participants received both treatments six months apart, in either order. Masking is listed as none.
The primary outcome was patient-reported injection-site burning and/or stinging on a 0-100 mm VAS approximately 15 minutes after injection. In the per-protocol population, the leuprolide acetate mean was 23.87, with a 95% confidence interval of 19.98 to 27.76; the triptorelin pamoate mean was 5.84, with a 95% confidence interval of 1.95 to 9.73. Each treatment result lists 107 participants.
The registry does not post a comparative analysis, details of missing-data handling, or the trial's own sample-size justification. It records zero serious and zero other adverse events in each treatment group; death counts are not reported in the registry record.