The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone) (NCT01386606), a randomized phase 2 study. The primary outcome is 24 Hour Average and Maximum Testosterone Concentration.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, single-blind, parallel-group Phase II study sponsored by Repros Therapeutics Inc. It lists enrollment of 60 and the status as completed. The study start is recorded as 2011-06, with primary completion in 2011-10. The condition is secondary hypogonadism.

Four treatment arms are described: Androxal 6.25 mg/day, Androxal 12.5 mg/day, Androxal 25 mg/day, and AndroGel 5G topical testosterone. The brief summary says the study would assess three doses of Androxal against AndroGel after 6 weeks of continuous dosing. It describes the intended participants as men with low testosterone, defined as <350 ng/dL. The official title instead describes normal healthy men, a population-description inconsistency not explained in the registry record.

The primary efficacy endpoint is 24-hour average and maximum testosterone concentration, compared with baseline at Week 6. Testosterone concentration was measured at time points from 0 through 24 hours after dosing, with the record listing each hourly time point. The primary analysis population is described as ITT, defined in the record as participants who received at least one dose and had at least one post-dose efficacy measure.

The record does not report the randomization procedure, the identity of the blinded party, site count, allocation ratios, or details of treatment adherence. It also does not describe the intended sample-size rationale. Although the study is marked completed, completion status alone does not establish what results were obtained or how completely outcomes were reported.

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: ITT, subjects who received at least one dose of study drug and had at least one post-dose efficacy 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.

Population: The baseline analysis consisted of all subjects enrolled.

6. Primary Endpoint

The registry lists the primary outcome as 24 Hour Average and Maximum Testosterone Concentration, measured over Baseline and Week 6.

The primary endpoint measures testosterone across a full 24-hour period after dosing. The record identifies two summaries: 24-hour average testosterone concentration, labelled TTavg, and maximum testosterone concentration, labelled TTmax. Both are expressed in ng/dL. Measurements are specified at hourly time points from 0 through 24 hours after dosing, and the endpoint compares Week 6 with baseline.

Average concentration describes the overall level across the measurement period, while the maximum captures the highest measured concentration in that period. As a general statistical point, these summaries can represent different features of a concentration profile: a mean reflects the level across observations, whereas a maximum is especially sensitive to the highest observed value. Neither summary alone describes every aspect of the profile, such as when the maximum occurs or how concentrations vary between measurements.

The registry record identifies the endpoint but does not report its group-level values, changes from baseline, uncertainty estimates, or comparison results. It is therefore not possible to judge from this record how large or precise any observed change was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: testosterone concentration is measured in ng/dL and summarized as a mean and a maximum. The registry record identifies the mean as the parameter and standard deviation as the dispersion measure. A mean describes the central level of measurements, while a standard deviation describes how spread out individual measurements are around that mean. They answer different questions: the mean concerns the typical level, and the standard deviation concerns variability among observations.

The endpoint has two summaries, TTavg and TTmax, measured at baseline and Week 6. The specified sampling schedule covers time points from 0 to 24 hours after dosing. Repeated measurements across a dosing interval provide information about the concentration profile, while the average and maximum reduce that profile to selected summaries. As a general statistical point, summaries simplify complex data and may conceal details that would matter for understanding the timing or variability of concentrations.

A treatment comparison could be expressed using group-level means or changes from baseline, but the registry record does not report those values or the analysis used to estimate them. It does not state whether the primary comparison used Week 6 values, change from baseline, an adjusted model, or another approach. The endpoint description says the Week 6 concentration is compared to baseline, but does not specify the statistical model or contrast.

Confidence intervals are a general way to communicate the precision of an estimate. They show a range of values compatible with the data and the assumptions of the analysis; narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. No confidence intervals for efficacy outcomes are reported in the registry record. P values, standard errors, test statistics, and the corresponding statistical tests are also not reported there. Thus, no inference about statistical significance or precision can be drawn from numerical efficacy estimates in this record.

When data are more variable than a statistical model assumes, standard errors and tests can be unreliable. In general, over-dispersion refers to variability greater than expected under a model, and methods that account for it can improve uncertainty estimates. The record specifies standard deviation as the dispersion measure for the continuous outcome but does not report a model, a variance assessment, or any adjustment for over-dispersion. There is no basis in the registry record to say whether over-dispersion was present or how it was addressed.

Multiple comparisons are relevant because the study includes three Androxal doses, a comparator, two primary endpoint summaries, and multiple outcome measures and analyses. As a general principle, testing many hypotheses can increase the chance of finding an apparently notable result by chance if no adjustment or hierarchy is used. The registry record lists 7 outcome measures and 14 analyses, but it does not report a multiplicity strategy, a hierarchy of endpoints, or which comparisons were designated as primary for inference.

The registry describes an ITT population as participants who received at least one dose and had at least one post-dose efficacy measure. This definition is important for interpreting results because it states which participants were intended to contribute to the efficacy analysis. The record does not report the number analyzed for each endpoint, whether all randomized participants met this definition, or how participants with missing post-dose data were handled. It also does not give reasons for missing measurements or describe imputation, sensitivity analyses, or other missing-data methods.

The record includes a sample-size-planning description based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, planning quantities are expressed as participants per arm; time-to-event quantities are described as total events. These are planning illustrations, not observed power. The numerical planning outputs and a trial-specific sample-size justification are not reported in the registry record. The record also does not explain how a two-arm planning assumption relates to this study's four listed arms.

No recalculated efficacy estimate is available from the posted information described in the record. There are no reported group means or standard deviations from which to reconstruct an unadjusted comparison. Accordingly, there is no recalculated result to distinguish from a sponsor analysis, and no basis to compare a reconstruction with the sponsor's own analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record describes several sources of multiplicity: three Androxal doses, an AndroGel comparator, two primary endpoint summaries, and additional outcome measures. It lists 7 outcome measures and 14 analyses. It also notes that the primary outcome has several categories or time points and was not reduced to one comparison. These details mean that the primary question is not represented by a single contrast in the posted record.

The registry does not report whether the analyses followed a prespecified hierarchy, whether comparisons among doses were planned, or whether any adjustment was made for multiple testing. It does not identify which analyses were confirmatory and which were exploratory. As a general statistical consideration, the interpretation of multiple estimates depends on the analysis plan: unadjusted tests across many outcomes and comparisons do not have the same error properties as a prespecified strategy that controls multiplicity. The registry record does not provide enough information to determine which approach was used.

Missing-data handling is also not reported. The record does not state how many participants had endpoint measurements available at baseline and Week 6, how missing measurements were treated, or whether sensitivity analyses assessed the impact of missingness. The ITT population is defined as participants who received at least one dose and had at least one post-dose efficacy measure. The number included in each analysis and any exclusions are not reported in the registry record.

The record does not describe interim analyses or give a statistical analysis plan. It also does not report a trial-specific sample-size justification. These omissions limit assessment of the intended inferential framework, but they do not establish that such procedures were absent; they are simply not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events by treatment group. It records 0 participants affected in the Androxal 6.25 mg group, with 16 at risk; 0 affected in the Androxal 12.5 mg group, with 14 at risk; 0 affected in the Androxal 25 mg group, with 16 at risk; and 0 affected in the AndroGel group, with 14 at risk. The top serious-event terms list is empty.

These entries describe what the registry reports for the listed groups; they do not establish that no serious events occurred outside the record's captured scope. The registry does not report the method or duration of adverse-event surveillance, or further details about serious-event definitions and ascertainment. Death counts are not reported in the registry record.

The record also lists other adverse events affecting 2 participants in the Androxal 6.25 mg group, 1 in the Androxal 12.5 mg group, 1 in the Androxal 25 mg group, and 4 in the AndroGel group. These are separate from the serious-event entries and should not be treated as serious adverse events. The registry counts are descriptive; without fuller event details and follow-up information, they do not by themselves characterize comparative safety.

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

The trial was designed to compare three Androxal dose groups with AndroGel on 24-hour average and maximum testosterone concentration, assessed at baseline and Week 6. The registry record identifies the population description, treatment arms, endpoint, and an ITT definition. It also reports group-specific serious adverse-event counts and counts for other adverse events.

What the record does not report is central to interpreting efficacy: there are no numerical group results for TTavg or TTmax, no changes from baseline, and no uncertainty estimates. It is therefore not possible to determine from the record whether the endpoint values increased or decreased, how large any change was, how the arms compared, or how precise an estimate might be. No statement that a treatment did or did not produce an effect is justified by the absence of these results.

The study's design features do not fill that gap. Randomization describes how participants were assigned in principle, but the allocation procedure is not reported. Single blinding is recorded, but the blinded party is not identified. The registry's completed status indicates that the study is marked completed; it does not supply the missing efficacy estimates or show how fully outcomes were reported.

The serious adverse-event entries show 0 affected participants in each listed group, with group-specific numbers at risk reported. Those descriptive counts should be interpreted in light of the limited safety detail in the record. They do not capture the full clinical context of events, exposure, timing, or ascertainment, and they do not answer the efficacy question.

Thus, the record allows a clear description of what the investigators set out to measure and the groups they intended to compare. It does not allow a quantitative assessment of comparative efficacy, endpoint precision, or the robustness of the analysis. These are limits of the registry record, not evidence for or against an effect.

13. Why This Trial Matters Statistically

This study illustrates why a well-defined endpoint and a complete results record are both important for statistical interpretation. The registry specifies a concentration profile assessed across 24 hours and identifies two distinct summaries, the average and the maximum. These summaries capture different aspects of the measurements, so the research question is broader than a single mean comparison.

There are three Androxal dose groups and an AndroGel comparator, while the registry lists 7 outcome measures and 14 analyses. That structure makes it important to know which contrasts were planned, how the primary endpoint components were prioritized, and whether multiplicity was addressed. Those details are not reported in the registry record. Without them, readers cannot readily distinguish a central confirmatory comparison from other analyses.

The record also demonstrates that study status and outcome reporting are separate issues. The trial is marked completed, and its endpoint timing and analysis population are described, but numerical efficacy results are not reported. A completed study record can still leave the principal estimates and their uncertainty unavailable for evaluation.

Finally, the population descriptions differ: the registry title and brief summary refer to men with secondary hypogonadism or low testosterone, while the official title refers to normal healthy men. That difference matters when judging how directly the study question applies to the population named in the record. The registry does not explain the discrepancy. Together, the absent efficacy estimates, unclear population wording, and limited analysis details make this record useful for understanding the planned measurement strategy but insufficient for evaluating comparative efficacy statistically.

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.

Several trial-specific limitations affect interpretation of the registry record. First, numerical results for the primary endpoint are not reported. There are no group-level testosterone summaries, baseline changes, confidence intervals, or test results with which to assess comparative effects or precision. The record describes the endpoint in detail but does not supply the results needed to answer the efficacy question.

Second, the study has four treatment arms and a primary endpoint with both average and maximum summaries, while the record lists 7 outcome measures and 14 analyses. It does not report a multiplicity strategy or identify the confirmatory comparisons. This makes the intended hierarchy of statistical evidence unclear.

Third, key design and analysis details are not reported: the method of randomization, who was blinded, the analysis model, handling of missing data, analysis counts by outcome, and any interim analyses. The ITT definition requires at least one dose and at least one post-dose efficacy measure, but the record does not report how many participants contributed to each endpoint.

Fourth, the record's population descriptions are not consistent. The title and brief summary describe men with secondary hypogonadism or low testosterone, while the official title describes normal healthy men. The registry does not clarify which description should guide interpretation.

Finally, the sample-size information is described as a planning illustration rather than a trial-specific justification, and numerical planning outputs are not reported in the registry record. The posted safety counts also lack details about event ascertainment and follow-up. These limitations constrain interpretation of this record; they do not show that unreported methods or data were absent from the study itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone) — NCT01386606.
• Registry record last updated 2015-09-23; status last verified 2015-08.
• Results first posted 2015-09-23.
• 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

NCT01386606 is recorded as a completed, randomized, single-blind, parallel-group Phase II study sponsored by Repros Therapeutics Inc. The record lists enrollment of 60 and four arms: Androxal 6.25 mg/day, Androxal 12.5 mg/day, Androxal 25 mg/day, and AndroGel 5G topical testosterone. The primary endpoint is 24-hour average and maximum testosterone concentration at baseline and Week 6, with measurements scheduled at time points from 0 through 24 hours after dosing.

The primary analysis population is described as ITT, requiring at least one dose and at least one post-dose efficacy measure. The record lists 7 outcome measures and 14 analyses. Numerical efficacy results, analysis details, missing-data methods, and multiplicity handling are not reported in the registry record. Serious adverse-event entries show 0 affected participants in each arm; death counts are not reported.