Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus (NCT01191320), a randomized phase 2 study. The primary outcome is Change in HbA1C.

2. Clinical Question

The registry describes the study as investigating the effect of Androxal on glycemic control in men with type 2 diabetes and secondary hypogonadism. Its primary endpoint focuses on change in HbA1c, a continuous measure used to assess glycemic control. The posted result gives a mean change for each arm and mean differences between each Androxal dose and placebo.

This is a question about the study’s recorded endpoint and comparisons, not a conclusion about treatment benefit. The registry record gives the mean changes as 0.0 for placebo, Androxal 12.5 mg and Androxal 25 mg. Both posted mean differences versus placebo are also 0.0. The confidence intervals and unadjusted p-values provide additional information about uncertainty in those comparisons. The registry does not report further outcome analyses.

3. Trial Design

The registry describes NCT01191320 as a completed, randomized, quadruple-masked, parallel-group Phase 2 study sponsored by Repros Therapeutics Inc. The recorded enrollment is 102. The study start is listed as 2010-10 and primary completion as 2011-12. Its listed conditions are type 2 diabetes mellitus and secondary hypogonadism.

Participants were assigned to placebo or one of two Androxal dose arms: 12.5 mg/day or 25 mg/day. The registry’s primary outcome description identifies the ITT population and specifies the change in HbA1c from baseline to 3 months for each treatment arm. The posted endpoint group sizes are 43.0 for placebo, 38.0 for Androxal 12.5 mg and 35.0 for Androxal 25 mg.

Randomization and masking are relevant design features: random allocation is intended to make treatment groups comparable on average, while masking can limit the influence of treatment knowledge on care, measurement or assessment. These are general methodological purposes, not evidence that any particular bias was eliminated in this trial. The registry record does not give further details about the randomization procedure, concealment, who was masked, or how masking was maintained.

The registry lists one outcome measure and no posted analyses. The detailed statistical analysis plan, including any model adjustments or planned contrasts, is not reported in the registry record. The posted mean differences and unadjusted p-values should therefore be read as the results recorded for the listed comparisons, not as a complete account of an unreported analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: ITT population

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: Safety population

6. Primary Endpoint

The registry lists the primary outcome as Change in HbA1C, measured over 3 months.

The primary endpoint is change in HbA1c from baseline to 3 months, summarized as a mean for each treatment arm. HbA1c is used in clinical research as a measure related to glycemic control over time. As a continuous endpoint, it can represent the magnitude and direction of change rather than only whether a participant crossed a defined threshold. This is a general explanation of the measure; the registry does not describe the laboratory procedure or provide further clinical interpretation of the endpoint.

The unit is recorded as Ratio, and the reported dispersion is standard deviation. The outcome description specifies the ITT population. The posted mean change is 0.0 in each arm. Each dose comparison is expressed as a mean difference against placebo, also recorded as 0.0. A zero mean change does not mean that every participant had no change; it describes the arm-level mean. Individual participant results and the distribution of changes are not reported in the registry record.

HbA1c is relevant to the trial’s stated question because the study aimed to assess glycemic control in men with type 2 diabetes and secondary hypogonadism. The three-month timeframe defines when the endpoint was assessed, but the registry record does not provide other follow-up results or explain whether additional time points were collected.

7. Results Posted in the Registry

• Androxal 12.5 mg: mean 0.00 versus 0.00 on control; difference 0.00 (95% CI -0.01 to 0.01), standardized effect d = 0.00; z-test p = 1.000.
• Androxal 25 mg: mean 0.00 versus 0.00 on control; difference 0.00 (95% CI -0.00 to 0.00), standardized effect d = 0.00; z-test p = 1.000.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, reported as a mean change in HbA1c. The registry gives the mean and standard deviation for each arm, then gives mean differences between each Androxal dose and placebo. A mean summarizes the center of a group’s observed values; a standard deviation describes how spread out those values are around the mean. These are general statistical interpretations. The registry does not provide participant-level observations.

What does a mean difference represent?

A mean difference compares the average outcome in one arm with the average in another. Here, placebo is the comparator for both Androxal doses. The recorded mean difference is 0.0 for each comparison, matching the posted arm means, which are also 0.0. Because the outcome is change from baseline, the contrast concerns mean change over the stated timeframe, not the absolute HbA1c level at baseline or at follow-up. Neither baseline values nor final values are reported in the registry record.

The comparison estimates are unadjusted as presented in the registry. An unadjusted comparison does not account for covariates unless that is part of the stated method. The registry record does not describe a model, covariate adjustment, or other details sufficient to determine whether further analysis was performed outside the posted results. The posted figures should therefore be read as the estimates and unadjusted p-values recorded for these comparisons.

How should the confidence intervals be read?

A confidence interval gives a range of estimates consistent with the observed data under a specified method. In repeated use of the same method under its assumptions, intervals constructed at a stated confidence level have a long-run coverage interpretation. A confidence interval is not a guarantee that the true effect lies inside the particular interval, nor is it a direct probability statement about the effect. The registry record does not state the confidence level or describe the interval calculation, so those details are not reported in the registry record.

The interval for the 12.5 mg comparison is -0.006 to 0.006. The interval for the 25 mg comparison also crosses zero. Intervals crossing zero indicate that the data do not distinguish the estimated contrast from zero at the interval’s stated coverage level, but the interval alone does not establish equivalence. The breadth of an interval is one way to assess precision: wider intervals allow a broader range of values, while narrower intervals constrain the range more tightly, subject to the method and assumptions.

What does the p-value add?

The registry reports an unadjusted p-value of 1.0 for each dose comparison. In general, a p-value is calculated under a null hypothesis and statistical model, and describes how unusual the observed data or a more extreme result would be if that model were correct. It does not measure the size or clinical importance of an effect, and it is not the probability that the null hypothesis is true. A large p-value is not proof that groups are the same. The test specification and analysis plan are not reported in the registry record, limiting interpretation beyond the posted value.

Multiplicity concerns arise when multiple hypotheses are tested, because repeated testing can change the chance of false-positive findings. There are two posted dose-versus-placebo comparisons, but the registry does not state whether these were the only planned comparisons or how multiplicity was handled. The p-values are explicitly unadjusted; no adjustment should be presumed.

How should the planning illustrations be understood?

Sample-size calculations are planning tools that describe the group size associated with chosen assumptions; they are not a measure of what the completed study actually had power to detect. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect defined as a fraction of the observed effect. These assumptions describe the planning illustration, not necessarily the trial’s original design. The registry record does not report the original sample-size justification.

Because the observed mean differences are recorded as 0.0, an illustration anchored to a fraction of the observed effect needs cautious interpretation. It should not be read as observed power or as evidence that the study was adequately sized for any clinically relevant difference. The planning illustration cannot replace a prespecified target difference and design assumptions from the trial protocol, which are not reported in the registry record.

10. Confidence Intervals and Precision

Precision concerns how tightly the data estimate a treatment contrast. The registry reports a mean difference of 0.0 for both Androxal comparisons. For 12.5 mg, the confidence interval ranges from -0.006 to 0.006. For 25 mg, the recorded interval crosses zero as well, with endpoints that are not restated because they contain more than three decimal places. Both intervals allow values on either side of no difference.

An interval that includes zero does not show that the true contrast is zero. It indicates that zero is among the values compatible with the data under the interval method. Conversely, the point estimate at zero does not mean that the estimate is perfectly precise. The interval conveys uncertainty that the point estimate alone cannot show. Whether the intervals exclude effects large enough to matter depends on a clinically justified threshold; such a threshold is not reported in the registry record.

The reported standard deviations are 0.012 for placebo, 0.015 for Androxal 12.5 mg and 0.01 for Androxal 25 mg. These describe variability in the arm-level endpoint, not uncertainty in the mean difference by themselves. The registry also posts group sizes for the primary outcome. Together, group size and variability influence precision, but the individual records, interval confidence level and calculation method are not reported in the registry record.

The intervals should not be treated as a substitute for the missing analysis details. The registry does not report whether the comparison accounts for baseline HbA1c or other factors. It also does not provide missing-outcome counts or sensitivity analyses. These omissions make it difficult to assess how robust the apparent lack of separation is to alternative analytic choices. The reported confidence intervals describe uncertainty under their calculation method, not every source of uncertainty in the conduct or reporting of the study.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted analyses. It presents two dose-versus-placebo comparisons for the primary endpoint, each with an unadjusted p-value. No multiplicity procedure or hierarchy of hypotheses is reported in the registry record. If several comparisons or outcomes are tested, multiplicity can affect the interpretation of nominal p-values; whether that issue was addressed in the trial’s planned analysis is not reported in the registry record.

The primary outcome description names the ITT population, a population definition generally intended to analyze participants according to randomized assignment. The registry does not report how the ITT population was operationalized, how missing endpoint measurements were handled, or whether all randomized participants contributed to the posted endpoint summaries. No imputation method, sensitivity analysis, or reasons for missing data are reported in the registry record.

The primary endpoint group sizes are reported as 43.0 for placebo, 38.0 for Androxal 12.5 mg and 35.0 for Androxal 25 mg. Adverse-event risk figures are separately recorded as 43, 38 and 38. In particular, the endpoint and adverse-event entries differ for the 25 mg group. The registry record does not explain this difference, so the entries should be retained as reported rather than reconciled by assumption.

The statistical analysis plan, model details, baseline adjustment, handling of protocol deviations and treatment of missing observations are not reported in the registry record. Without these details, it is not possible to determine whether the posted summaries reflect all planned analyses or whether additional analyses were conducted but not posted. These limitations do not invalidate the recorded figures, but they restrict how completely the analytic choices and their consequences can be assessed.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: coronary bypass (2.6%), angina pectoris (2.3%).

The registry reports serious adverse events affecting 1 participant in the placebo group, 0 in the Androxal 12.5 mg group and 1 in the Androxal 25 mg group. The associated risk figures are 43, 38 and 38, respectively. These counts describe the posted serious-event entries; they do not establish that an event was caused by the assigned treatment. The registry does not give a causal assessment in the listed information.

The registry also lists coronary bypass at 2.6% and angina pectoris at 2.3% among the top serious-event terms. These percentages are not assigned to a particular treatment arm in the record presented, so they should not be interpreted as arm-specific rates. Death counts are not reported in the registry record.

Adverse-event counts are descriptive. They are influenced by the length and completeness of observation, event definitions and reporting practices. The registry entry does not provide detailed event narratives, exposure time, severity grading beyond the serious-event classification, or an account of how events were judged related to treatment. The risk figures for the adverse-event listing also differ from the endpoint group size for the 25 mg arm; the record does not explain why. These entries therefore support a description of what was posted, not a comparative safety conclusion.

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

The posted primary endpoint shows an arm-level mean HbA1c change of 0.0 for placebo and for both Androxal doses. The mean difference against placebo is also recorded as 0.0 for each dose. The confidence intervals cross zero, and the unadjusted p-values are 1.0. Together, these results describe no separation in the reported point estimates, while retaining uncertainty around the contrasts.

These findings do not establish that the treatments are equivalent, nor do they rule out an effect. A conclusion of equivalence requires a prespecified margin and an analysis designed to assess whether the plausible differences fall within that margin. Neither is reported in the registry record. A non-significant or large p-value is not proof of no effect, and a point estimate of zero should not be mistaken for proof that every participant’s outcome was unchanged.

The registry record does not report individual outcomes, baseline or final HbA1c values, missing-data handling, the confidence level, or the detailed statistical plan. The posted summary therefore cannot show the range of participant-level responses or how the result might change under alternative modeling assumptions. The endpoint is limited to the stated 3-month timeframe; the record does not provide later outcome results.

The safety figures likewise describe reported counts and terms, rather than establishing treatment causality or a complete comparative safety profile. Death information is not reported in the registry record. In addition, the adverse-event risk figures and endpoint group sizes differ for the 25 mg arm, and the reason is not explained.

The appropriate reading is narrow: these are the recorded group summaries and unadjusted comparisons for the primary endpoint, alongside limited adverse-event information. They do not support advice for an individual or a broad claim about treatment effectiveness. Interpretation beyond the registry’s posted data would require details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a point estimate and the uncertainty around it. The posted mean differences are 0.0, but the confidence intervals are not point values: they include values on either side of zero. A reader should therefore distinguish the observed estimate from the range of effects compatible with the data under the interval method. The p-values add a test-based summary but do not replace that assessment of precision.

The record also highlights why a large p-value cannot be treated as proof of equivalence. Equivalence requires a defined margin and a design and analysis suited to comparing the estimate with that margin. Such details are not reported. The distinction matters whenever an analysis is read as showing “no difference” merely because its test did not identify a nonzero contrast.

Another statistical lesson is the importance of clear denominators. The endpoint group sizes and adverse-event risk figures are not identical for the 25 mg arm. Without an explanation in the registry record, those entries should remain distinct rather than being combined or silently reconciled. Clear reporting of analysis populations and event denominators is essential for evaluating summaries.

Finally, the registry records the primary endpoint but no additional analyses and does not report its detailed statistical plan. This limits evaluation of multiplicity, covariate adjustment and missing-data handling. The study therefore provides a useful example of how to read posted estimates carefully while recognizing the boundaries of a registry summary.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific gaps limit interpretation. The registry identifies the ITT population for the primary endpoint but does not explain how that population was defined in practice, whether all randomized participants contributed outcome data, or how missing measurements were handled. Missing-data counts, reasons and sensitivity analyses are not reported in the registry record.

The statistical analysis plan and model specification are also not reported. The record does not state whether the analysis adjusted for baseline HbA1c or other variables, how the confidence intervals were calculated, or what test produced the unadjusted p-values. It does not describe any multiplicity procedure. These omissions prevent a full assessment of analytic choices from the posted summary alone.

The endpoint group sizes are 43.0 for placebo, 38.0 for Androxal 12.5 mg and 35.0 for Androxal 25 mg. The adverse-event risk figures are 43, 38 and 38, respectively. The registry record does not explain the 25 mg denominator difference. Individual participant outcomes and additional endpoint time points are also not reported.

The posted primary result is limited to mean change at 3 months. No baseline or follow-up arm means beyond the change summaries, subgroup analyses, or secondary outcome results are posted. The registry lists one outcome measure and no posted analyses. The record also does not report the original sample-size justification, so the planning assumptions should not be taken as evidence of the original design rationale or observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus — NCT01191320.
• Registry record last updated 2014-07-24; status last verified 2014-06.
• Results first posted 2014-07-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01191320 is a completed randomized, quadruple-masked, parallel-group Phase 2 study of Androxal versus placebo in men with type 2 diabetes mellitus and secondary hypogonadism. The registry records enrollment of 102 and lists Androxal doses of 12.5 mg/day and 25 mg/day.

The primary endpoint is mean change in HbA1c from baseline to 3 months in the ITT population. The posted mean change is 0.0 in all three arms, and both mean differences versus placebo are 0.0. The unadjusted p-value is 1.0 for each comparison. The confidence intervals cross zero.

The registry also reports serious adverse-event counts and selected serious-event terms, but deaths are not reported in the registry record. Detailed statistical methods, missing-data handling, multiplicity procedures and further analyses are not reported in the registry record.