Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L]): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L]) (NCT00328926), a randomized phase 4 study. The primary outcome is Time to Clinical Pregnancy.

2. Clinical Question

The central statistical question is whether the observed time-to-pregnancy summaries differ among the listed treatment arms, and how precisely the record can answer that question. The record describes a randomized, quadruple-masked, parallel-group Phase IV study. However, the endpoint-evaluable groups were very small, and the registry does not report a hazard ratio, confidence interval, p-value, or other inferential comparison. Consequently, the posted medians describe the evaluable participants; they do not establish a comparative treatment effect.

3. Trial Design

This was a Phase IV, multicenter, randomized, double-blinded trial with a parallel-group model and quadruple masking. The official title describes a comparison of Luveris® 75 IU with placebo when administered with follitropin alfa, in women with profound LH deficiency. The registry also lists a Luveris® 25 IU arm. It lists recombinant human follicle stimulating hormone and recombinant human chorionic gonadotropin among the interventions. Detailed arm descriptions and the allocation ratio are not reported in the registry record.

Enrollment is recorded as 11. The trial began in 2006-03, and primary completion is recorded as 2012-05. Its status is terminated. The brief summary says the sponsor decided to discontinue Luveris® in the United States because of customer demand, not because of efficacy or safety concerns. That statement explains the reported discontinuation rationale; it does not supply an efficacy or safety conclusion from the study results.

The primary endpoint is reported for an intention-to-treat population defined as all participants who received study treatment, while the record clarifies that the reported N for the measure denotes participants evaluable for it. The endpoint-evaluable Ns differ by arm: 3.0 for Luveris® 75 IU, 1.0 for Luveris® 25 IU and 1.0 for placebo. The registry record does not explain the relationship between these endpoint-evaluable counts and the overall enrollment, or give a participant-flow account by arm.

Two secondary outcomes are listed: cumulative clinical pregnancy and cumulative ovulation. The registry reports no analyses for the trial. Randomization and masking describe design features, but they do not by themselves provide estimates of comparative effects or resolve the limitations of the small endpoint-evaluable groups.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population included all the participants who received study treatment. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

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 Time to Clinical Pregnancy, measured over Stimulation Day 1 up to clinical pregnancy (Day 35-42 post r-hCG administration day [end of stimulation cycle {approximately 21 days}]).

The primary outcome is time to clinical pregnancy, measured in days from stimulation Day 1 to clinical pregnancy. The registry defines clinical pregnancy as the presence of one or more fetal sacs with fetal heart activity on the ultrasound examination conducted on Day 35–42 after r-hCG administration. The stated timeframe extends from stimulation Day 1 up to clinical pregnancy, with the end-of-cycle timing described as approximately 21 days.

A time-to-event endpoint records how long it takes for a specified event to occur. In general, it can retain information about timing that a simple yes-or-no outcome by a fixed point would not convey. The median is the middle of the observed time distribution: it describes a typical event time in the evaluated group, not the average time and not an individual participant’s expected time. The registry reports the median and full range for each arm, rather than a hazard ratio or a model-based comparison.

The measure is relevant to the trial’s stated aim of inducing follicular development and pregnancy, but the registry’s endpoint definition is specifically based on ultrasound evidence of clinical pregnancy. It is not a measure of pregnancy alone in any broader sense, nor does the record establish that all participants had the event. The endpoint description says that N denotes participants evaluable for this measure. How participants without an evaluable outcome were handled is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the median report?

General: A median is the central value when observations are ordered. For a time endpoint, it expresses the time by which the middle of the observed distribution has experienced the event, subject to the analysis method and available follow-up. It is different from a mean, which averages observed values, and it does not describe how far apart all participant outcomes are. In this record, the endpoint is reported as a median with a full range, so the summaries give a central time and the smallest and largest reported times, rather than a standard deviation or confidence interval.

The reported values are 71.0 days (range 47.0 to 116.0) for Luveris® 75 IU, 51.0 days (range 51.0 to 51.0) for Luveris® 25 IU, and 103.0 days (range 103.0 to 103.0) for placebo. Their respective endpoint-evaluable Ns are 3.0, 1.0 and 1.0. The single-observation arms cannot provide an empirical account of within-arm variability: the sole observation is also the median and both range limits. The range in the 75 IU arm displays the spread of its few reported observations, but it is not a measure of uncertainty around the median.

Why is this a time-to-event outcome?

General: Time-to-event methods are designed for outcomes defined by the time until an event, such as the clinical pregnancy specified in this trial. In a complete time-to-event analysis, participants who have not experienced the event by their last observed time may contribute censored follow-up rather than being treated as though the event occurred then. This distinction can affect estimates and comparisons. The registry record does not report the number of participants without the event, censoring details, follow-up completeness, or the method used to calculate the displayed medians. No assumptions about those procedures can be made from the posted results.

Some comparative time-to-event analyses report a hazard ratio. In general, that measure compares event rates over follow-up under a specified model; it is not the same as a difference between medians. The record describes the outcome as time-to-event, but no sponsor-reported hazard ratio or other comparative estimate is reported in the registry record. No hazard-ratio interpretation can therefore be attached to these summaries.

What do randomization and masking contribute?

General: Random assignment is intended to reduce systematic differences between treatment groups at the start of a study. Masking is intended to limit the influence of knowledge about assigned treatment on care, reporting or assessment. These are design safeguards, not statistical results. Their presence does not guarantee that groups are balanced, prevent missing data, or make estimates precise. The record identifies the study as randomized, parallel-group and quadruple-masked, but does not specify the allocation ratio or which roles were included in the masking description.

What can be inferred from the reported analysis?

The registry reports arm-level descriptive summaries only for the primary endpoint. It lists no analyses, and no p-value or confidence interval is reported for an arm comparison. General: A confidence interval, when reported, represents a range of values compatible with the data and the analysis assumptions at a stated confidence level. Its width conveys statistical precision; a p-value, when reported, summarizes how unusual the data would be under a specified null model. Neither can be reconstructed from these arm-level medians and ranges alone, particularly with the endpoint-evaluable Ns. The record does not provide a statistical analysis plan or identify an inferential test.

Because no formal comparative estimate is reported, the endpoint summaries should not be converted into a treatment effect or a claim of statistical significance. The missing inferential results cannot be replaced by visually comparing the medians, and the small endpoint-evaluable groups do not support reliable conclusions about the population distribution. Any sample-size illustration associated with a result should be understood as a planning calculation based on stated assumptions, not as observed power or as evidence that the original trial was designed to detect a particular effect. The registry record does not report the trial’s sample-size justification or statistical plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two secondary outcomes: percentage of participants with cumulative clinical pregnancy and percentage of participants with cumulative ovulation. It also records three outcome measures and zero analyses. No results for the listed secondary outcomes are included in the registry record, and no multiplicity strategy is reported.

Multiplicity arises when several outcomes, comparisons or analyses are considered. General: If many hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis plan accounts for that testing. Adjustments or a prespecified hierarchy can help control that risk, but the registry record does not say whether either approach was used. Since no analyses are reported, the effects of any multiplicity procedure cannot be assessed.

The primary outcome description defines the intention-to-treat population as participants who received study treatment. It separately clarifies that the N reported for this outcome represents participants evaluable for the measure. The endpoint-evaluable counts are 3.0 for Luveris® 75 IU, 1.0 for Luveris® 25 IU and 1.0 for placebo. No arm-by-arm accounting of participants who received treatment but were not evaluable is reported. Reasons for missing or unevaluable outcomes, methods for handling missing observations, and any sensitivity analyses are not reported in the registry record.

These omissions limit interpretation because the record does not establish whether the reported medians represent all treated participants or only those with usable endpoint data, beyond identifying the evaluable Ns. The record also does not report a statistical analysis plan, prespecified analysis population beyond the endpoint definition, or handling of participants who did not experience clinical pregnancy during follow-up. No assumptions about those choices should be made.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia pneumococcal (33.3%), pneumonia streptococcal (33.3%), abortion missed (20.0%).

The registry reports serious adverse events for each arm using an at-risk count and a count of participants affected. For Luveris® 75 IU, 5 participants were at risk and 1 was affected; for Luveris® 25 IU, 3 were at risk and 0 were affected; for placebo, 3 were at risk and 1 was affected. These are descriptive counts. They do not establish whether an event was caused by treatment, and they do not by themselves permit a reliable comparison of safety between arms.

The listed top serious adverse-event terms are Pneumonia pneumococcal at 33.3%, Pneumonia streptococcal at 33.3%, and Abortion missed at 20.0%. The registry record does not give the denominator or arm attribution for these percentages in the information, so they should not be assigned to a particular arm or interpreted as arm-specific risks. The affected counts for other adverse events are also reported: 4 of 5 at risk in the Luveris® 75 IU arm, 1 of 3 in the Luveris® 25 IU arm, and 3 of 3 in the placebo arm. These other-event counts are distinct from the serious-event counts.

Deaths are not reported in the registry record. This is not equivalent to a reported count of zero deaths. The brief summary states that discontinuation reflected customer demand in the United States, not efficacy or safety concerns; that statement does not replace a complete safety analysis.

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

The posted results establish that the registry contains descriptive median-time summaries for the primary endpoint among participants evaluable for that measure. They also identify a randomized, quadruple-masked, parallel-group Phase IV study and list the treatment arms, secondary outcomes and safety counts. The reported endpoint medians are 71.0 days for Luveris® 75 IU, 51.0 days for Luveris® 25 IU and 103.0 days for placebo, with the ranges and endpoint Ns described in the registry.

Those summaries do not establish that one arm caused a shorter or longer time to clinical pregnancy than another. A comparative estimate, its uncertainty and a statistical test are not reported. The small endpoint-evaluable Ns, including arms with an N of 1.0, further limit what can be inferred about typical times or variation in the broader population. Without participant-flow details and information on event-free follow-up, the medians cannot be treated as a complete account of all enrolled participants’ outcomes.

The safety counts similarly describe what the registry reports, not causal effects. The count of participants affected by a serious adverse event does not identify whether the event was related to study treatment. Serious-event term percentages are not accompanied by a denominator or arm attribution in the record, and deaths are not reported in the registry record. The sponsor’s stated reason for discontinuing Luveris® in the United States was customer demand, rather than efficacy or safety concerns, but that rationale does not supply a comparative treatment result.

In general, a randomized design can support causal comparisons when outcomes are adequately collected and analyzed under appropriate methods. Here, the registry’s descriptive endpoint information is insufficient to make such a comparison. The results should therefore be read as limited summaries of evaluable participants, not as proof of benefit, lack of benefit, or safety equivalence.

13. Why This Trial Matters Statistically

This trial is statistically instructive because a randomized design and masked treatment assignment do not ensure that a registry will contain enough outcome information for a meaningful comparison. Although enrollment is recorded as 11, the endpoint-evaluable Ns reported for the three arms are 3.0, 1.0 and 1.0. The primary endpoint is summarized with medians and full ranges, but no comparative analysis is reported. The distinction between enrollment and outcome-evaluable participants is important when judging what a result can support.

Time-to-event outcomes require attention to both event timing and follow-up. A median and range can describe the observed times, but they do not show the entire event pattern, account visibly for participants who have not had the event, or express uncertainty around a treatment comparison. The registry does not report the event and censoring details or inferential estimates needed for a fuller interpretation. A reader should not substitute a comparison of medians for a prespecified time-to-event analysis.

The record also illustrates why safety counts need context. At-risk denominators vary by arm, serious-event counts are small, and the listed serious-event percentages are not attributed to arms in the reported information. These figures are useful as a description of what was recorded, but they do not provide a robust comparative safety estimate.

Finally, the stated reason for trial termination is distinct from its statistical findings. The sponsor attributed discontinuation in the United States to customer demand and not to efficacy or safety concerns. That context helps explain the status, but it cannot fill gaps in the outcome analysis. The principal lesson is to separate trial design, descriptive results, inferential evidence and administrative reasons for discontinuation.

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 is the very small number of participants evaluable for the time-to-clinical-pregnancy outcome in each arm: 3.0 for Luveris® 75 IU, 1.0 for Luveris® 25 IU and 1.0 for placebo. With an N of 1.0, a median and range provide no information about variation among participants in that arm. The summaries from the arm with an N of 3.0 also rest on few observations and cannot precisely characterize a broader distribution.

The registry reports no inferential analyses for the primary endpoint. There is no reported hazard ratio, confidence interval, p-value, or adjusted comparison. The statistical analysis plan, sample-size justification, allocation ratio and interim-analysis information are not reported in the registry record. Consequently, the reason for the low endpoint-evaluable counts and whether the study was intended or able to estimate a particular effect cannot be determined from the record.

The record does not describe participant flow by arm, missing-outcome reasons, event-free follow-up, censoring, or methods for handling missing observations. Although the endpoint population is defined as participants who received study treatment, the reported N indicates those evaluable for the measure; the record does not reconcile those populations. Results for the two listed secondary outcomes are not reported, and a multiplicity approach is not reported.

Safety interpretation is also limited. The record supplies arm-specific at-risk and affected counts, but does not provide causal attribution. The serious-event term percentages are not accompanied by arm attribution or a stated denominator in the reported information, and deaths are not reported in the registry record. The termination explanation is administrative context and does not resolve these limitations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L]) — NCT00328926.
• Registry record last updated 2013-08-07; status last verified 2013-08.
• Results first posted 2013-07-12.
• 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.

18. Record Summary

NCT00328926 is a Phase IV, multicenter, randomized, quadruple-masked, parallel-group trial in women with hypogonadotropic hypogonadism and profound LH deficiency. It compared Luveris® 75 IU, Luveris® 25 IU and placebo in a follicular-stimulation setting. Enrollment is recorded as 11, and the trial status is terminated.

The primary endpoint was time to clinical pregnancy, defined by ultrasound evidence of one or more fetal sacs with fetal heart activity on Day 35–42 after r-hCG administration. The registry reports arm-specific medians and ranges for endpoint-evaluable Ns of 3.0, 1.0 and 1.0, respectively, but reports no analyses or inferential comparison. Two secondary outcomes are listed without results in the registry record.

The sponsor’s stated reason for discontinuation in the United States was customer demand, not efficacy or safety concerns. The record’s small endpoint-evaluable groups and missing comparative analyses limit interpretation of both the primary outcome and safety information.