A Study of Oral Calcitonin Given at Night to Healthy Postmenopausal Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Oral Calcitonin Given at Night to Healthy Postmenopausal Women (NCT00803686), a randomized phase 2 study. The primary outcome is Pharmacodynamic Effect of Oral Calcitonin.

2. Clinical Question

3. Trial Design

The registry identifies NCT00803686 as a Phase 2 randomized crossover study with completed status. It lists enrollment as 12. The study is titled as an investigation of oral calcitonin given at night to healthy postmenopausal women, with CTx-1 concentrations as the pharmacodynamic focus. The registry records a start date of 2008-12 and primary completion in 2009-01.

The study had two parts with different treatment settings. Part 1 compared an oral rsCT tablet with a matching oral placebo tablet, each given once 4 hours after the evening meal. The Part 1 descriptions identify the comparison as double blind. Part 2 was open label: oral rsCT was given once 2 hours after the evening meal and was considered alongside Fortical rsCT nasal spray, also given once 2 hours after the evening meal. The registry does not report the allocation sequence, treatment order, or washout interval.

The record classifies the overall model as crossover and describes each participant as serving as her own control for the primary outcome, with placebo included to account for known diurnal variation in CTx-1. However, it does not give enough detail to reconstruct the sequence or period structure. The masking field says triple masking, while the arm descriptions call Part 1 double blind and Part 2 open label; the registry does not explain this difference.

Numbers contributing to endpoint summaries are not identical across the posted Part 1 and Part 2 arms. The registry record does not explain the reasons for those differences. It also does not report a sample-size justification, a recruitment flow, or a detailed analysis population definition beyond stating that all participants who received treatment were included in the primary outcome population.

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.

Part 1, Period 1

Part 1, Period 2

Part 2, Period 3

Analysis population for the primary outcome, as defined in the registry: Not applicable. All participants who received treatment were included.

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: Only 12 women entered Part 1, the two-period crossover portion of the study; hence the same 12 received both oral treatments and should not be counted twice. Only 9 of those 12 went on to Part 2, the open label, non-crossover portion of the study.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacodynamic Effect of Oral Calcitonin, measured over 12 hr.

The primary endpoint is titled “Pharmacodynamic Effect of Oral Calcitonin.” It measures the minimum observed value of CTx-1 response after an active dose, expressed as a percentage of the time-matched placebo response. CTx-1 is a plasma biomarker described in the registry as an established index of bone-resorption activity in response to interventions such as calcitonin.

Using time-matched placebo values is relevant because the registry notes known diurnal variation in plasma CTx-1. In a crossover setting, comparison with each participant’s placebo response is intended to account for variation over the day as well as differences between participants. The record says that CTx-1 concentrations were collected over 12 hr after dosing, and that the ratio of calcitonin response to placebo response was derived at each time point. The minimum of those percentage values, Rmin, is the primary pharmacodynamic parameter.

The endpoint is a biomarker measure, not a clinical outcome. Its posted summaries describe group means and standard deviations for the minimum percentage of placebo response. Those summaries can show the observed distribution and its variability, but they do not by themselves establish a clinical effect. The registry record does not provide a sponsor-reported hypothesis test or confidence interval for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcomes are continuous measures. For a continuous endpoint, a mean describes the average value within an arm, while a standard deviation describes how spread out individual values are around that mean. Neither measure alone shows the uncertainty in the mean, and neither establishes whether an observed difference is statistically compatible with no difference. The registry posts means and standard deviations for the primary outcome arms but does not post a sponsor-reported primary-endpoint test or confidence interval.

What does the primary percentage represent?

At each measurement time, the registry says that each participant’s calcitonin response was compared with that participant’s time-matched placebo response. The resulting value was expressed as a percentage of placebo response, abbreviated %P in the outcome description. Rmin is the minimum value observed after an active dose. A value expressed in this way is relative to the corresponding placebo response; it is not a plasma concentration in the units of CTx-1. The endpoint’s stated timeframe is 12 hr.

The use of time-matched placebo values matters because CTx-1 has diurnal variation, as noted in the record. More generally, measurements that vary over time can be difficult to interpret if a treatment and a comparator are assessed at different times of day. Matching time points can make the comparison more informative about the observed response pattern, although it does not remove every possible source of bias or uncertainty.

How should the crossover structure be understood?

In general, a crossover design compares treatments within the same participant, which can reduce the influence of stable differences between participants. The registry states that each subject served as her own control and that all received placebo. That description supports interpreting the Part 1 placebo data as part of a within-participant control approach. However, the registry does not report treatment sequence, period-specific results, or washout details. Those omissions mean the exact analysis structure cannot be reconstructed from the record.

The record labels the study as crossover, but Part 2 is described as open label and its outcome summaries have different participant counts for the oral and nasal arms. The registry does not provide a sponsor-reported Part 2 comparison or enough detail to determine how its treatment assignments and periods were handled statistically. Therefore, direct numerical contrasts between the Part 2 arm means should remain descriptive.

What does the recalculated secondary comparison mean?

The posted secondary analysis is an unadjusted recalculation of the Part 1 AUC inhibition comparison. The reported mean difference is 474.7 hours*%P, and its 95% confidence interval runs from 323.2 to 626.2. The recalculated p-value is p < 0.001. A mean difference expresses the difference between two group means in the endpoint’s stated units. A confidence interval gives a range of values compatible with the estimated difference under the statistical model and assumptions used; it is not a guarantee that the true value lies within that interval.

The interval and p-value describe this recalculated comparison, not the primary Rmin endpoint. The registry record lists no sponsor-reported analyses for this secondary outcome. The recalculation is unadjusted, so its p-value does not account for testing multiple outcomes or comparisons. In general, repeated testing increases the chance that at least one result appears statistically notable by chance, which is why a prespecified multiplicity strategy can matter.

Why can over-dispersion matter?

In general, over-dispersion occurs when the observed variability is greater than a statistical model expects. It is most often discussed for count outcomes, where a simple model can understate uncertainty if the data vary more than assumed. The outcomes described in this study are continuous, and the registry does not report an over-dispersion analysis. More broadly, model assumptions should fit the endpoint and design; the registry’s limited analysis details prevent a full assessment of those assumptions.

How should planning illustrations be read?

The registry includes planning illustrations based on the observed secondary effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are not the trial’s original sample-size plan and are not observed power. Their values are given as participants per arm for 80% power and participants per arm for 90% power, for planning for 100%, 75%, or 50% of the observed effect. Such illustrations depend strongly on the effect chosen for planning. Using an effect estimated in a small study can produce optimistic planning values, so the figures should not be treated as proof that a future study would achieve those power levels.

These statistical concepts are general explanations. The registry record does not report the original sample-size justification, the primary statistical plan, an interim analysis plan, or a detailed method for handling missing observations. Those details cannot be inferred from the posted summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary pharmacodynamic outcome and also lists secondary pharmacodynamic outcomes. It does not report a multiplicity adjustment, a gatekeeping procedure, or a hierarchy specifying how primary and secondary hypotheses were to be tested. The posted recalculated AUC inhibition comparison is explicitly unadjusted. Its p-value should therefore be interpreted as applying to that comparison alone, not as a family-wise conclusion across all outcomes or treatment contrasts.

The record lists no sponsor-reported analyses. For the primary endpoint, arm means and standard deviations are posted, but the registry record does not report a sponsor-reported confidence interval or hypothesis test. For the secondary comparison, the confidence interval and p-value are identified as recalculated and unadjusted. This distinction matters because a recalculation from summary statistics is not the same as a prespecified sponsor analysis using participant-level data and the full crossover structure.

Missing-data handling is not reported in the registry record. The primary population is described as including all participants who received treatment, but the record does not explain how missing time points, incomplete periods, or incomplete outcome records were handled. It also does not provide a participant flow accounting for the differing numbers in the posted Part 2 summaries. The reason for those differences is not reported in the registry record.

The registry does not report an interim analysis plan, stopping rule, or sample-size justification. It also does not give sufficient detail to assess whether the statistical methods accounted for treatment sequence or period effects in the crossover design. These are reporting gaps, not evidence that a particular procedure was or was not used. Without those details, the posted results support a descriptive reading of the primary outcome and a cautious reading of the recalculated secondary comparison.

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 posted serious adverse event figures show zero participants affected in each listed treatment group: Part 1 oral rsCT tablets, Part 1 oral placebo tablets, Part 2 open-label oral rsCT tablets, and Part 2 open-label Fortical intranasal spray. The corresponding numbers at risk are 12, 12, 5, and 4. No serious adverse event terms are listed. Death counts are not reported in the registry record.

These figures describe the registry’s reported serious adverse event counts for the listed groups. They do not establish that no serious events occurred outside the recorded observation or reporting framework, and they do not provide a detailed account of event timing, severity gradation, or relatedness. The registry does not provide serious-event narratives or a longer-term safety assessment.

The record separately lists other adverse events affecting 1 participant in the Part 1 oral rsCT group, 3 participants in the Part 1 placebo group, none in the Part 2 oral rsCT group, and 1 in the Part 2 Fortical group. These are not serious adverse event counts. Because the study was small and the Part 2 groups have fewer participants represented in the posted safety summaries, the figures are descriptive and do not support a precise comparison of safety between treatments.

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

The results describe short-term pharmacodynamic measurements after nighttime dosing in healthy postmenopausal women. The primary endpoint uses CTx-1, a plasma biomarker identified in the registry as an index of bone-resorption activity. The Part 1 oral rsCT summary was expressed as a percentage of the time-matched placebo response, while the Part 1 placebo summary was 100.0. Part 2 posted descriptive summaries for oral rsCT and Fortical nasal spray.

These findings do not establish a clinical benefit, a change in fracture risk, or an effect on any clinical outcome. The registry reports biomarker measurements over 12 hr, not clinical outcomes. A biomarker response can characterize a biological measurement without proving that a patient-important outcome changes. Nor do the posted results establish how the treatments would compare in populations other than the healthy postmenopausal women enrolled in this study.

The primary endpoint summaries do not include a sponsor-reported inferential comparison in the registry record. The unadjusted recalculation pertains to a secondary AUC inhibition outcome and should not be substituted for a primary-endpoint analysis. The recalculated p-value and confidence interval describe uncertainty under the recalculation’s assumptions; they do not correct for multiple testing, missing analysis details, or limitations of the small study population.

The crossover design and time-matched placebo approach are relevant strengths for studying changing biomarker levels, because participants can serve as their own controls and diurnal variation is considered in the endpoint definition. At the same time, the registry does not provide sequence, washout, missing-data, or period-analysis details. Part 2 was open label, and the registry does not post a sponsor analysis of the oral-versus-nasal comparison. Therefore, the numerical summaries should be read as observations within this study’s design and not as definitive comparative evidence.

Overall, the record supports a cautious account of the observed pharmacodynamic patterns and the posted safety counts. It does not support treatment recommendations or conclusions beyond the measured outcomes and recorded study population.

13. Why This Trial Matters Statistically

This trial is statistically notable for its use of a crossover framework to study a biomarker with known diurnal variation. The registry describes each participant as serving as her own control and reports time-matched placebo response values. In general, within-participant comparisons can reduce the influence of stable differences between people, while matching measurement times can help address systematic changes over the day. These design features are directly relevant to interpreting a biomarker whose level changes with time.

The record also illustrates why design labels do not replace detailed analysis reporting. Although the overall model is called crossover, the registry does not report the treatment sequence, washout interval, or period-specific statistical model. It describes Part 1 as double blind and Part 2 as open label, while the masking field says triple masking. Without an explanation of these details, readers cannot fully reconstruct how the design was implemented or how its features were handled in analysis.

There is also a useful distinction between the primary endpoint and the secondary recalculation. The primary outcome is represented by descriptive arm summaries without a sponsor-reported inferential comparison. The secondary AUC inhibition comparison has a recalculated confidence interval and unadjusted p-value, but the record lists no sponsor-reported analyses and no multiplicity procedure. This highlights why statistical significance for one secondary comparison cannot stand in for a complete prespecified analysis.

Finally, the study’s small enrollment and differing numbers in the Part 2 outcome summaries make precision and representativeness important considerations. The registry does not report the original sample-size rationale. Planning illustrations based on the observed secondary effect are not observed power and are not the trial’s design justification. The record is therefore most informative as a compact example of pharmacodynamic endpoint construction, crossover considerations, and the limits of inference when analysis details are incomplete.

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 limitations are specific to the information recorded for this study. Enrollment was 12, and the posted outcome summaries include smaller numbers in the Part 2 arms. The registry does not explain why the numbers contributing to those summaries differ or whether the difference reflects missing measurements, eligibility for a particular part, or another reason. Those explanations are not reported in the registry record and should not be assumed.

The primary outcome is a biomarker measure observed over 12 hr, rather than a clinical outcome. The registry provides the endpoint definition and descriptive summaries but no sponsor-reported primary-endpoint test or confidence interval. This limits the assessment of precision and makes it inappropriate to present the primary summaries as a definitive statistical comparison.

The record’s design descriptions are not fully reconciled. It identifies the overall study as crossover and says participants served as their own controls, while Part 2 is open label and the masking field states triple masking. Treatment sequence, washout, period effects, and the analysis used to account for the crossover structure are not reported. The record also does not report a detailed missing-data method or a participant flow explaining the numbers in each outcome group.

The secondary AUC inhibition comparison is a recalculation from posted summary statistics and is unadjusted. No sponsor-reported analyses are listed, and multiplicity handling is not reported. The registry also does not report the original sample-size justification, interim analyses, or a complete statistical analysis plan. These gaps limit interpretation of both statistical uncertainty and the intended role of the secondary results.

Finally, the population was healthy postmenopausal women, and the reported measurements concern short-term nighttime pharmacodynamic responses. The findings cannot on their own establish effects in other populations or on clinical outcomes not measured in the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Oral Calcitonin Given at Night to Healthy Postmenopausal Women — NCT00803686.
• Registry record last updated 2014-06-09; status last verified 2014-06.
• Results first posted 2014-06-09.
• 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

NCT00803686 is a completed Phase 2 randomized crossover study of nighttime oral recombinant salmon calcitonin in healthy postmenopausal women. The registry lists enrollment of 12 and primary completion in 2009-01. Part 1 compared oral rsCT with matching oral placebo; Part 2 was open label and included oral rsCT and Fortical nasal spray.

The primary outcome was the minimum CTx-1 response expressed as a percentage of time-matched placebo response over 12 hr. The registry posts descriptive primary summaries but no sponsor-reported inferential primary analysis. It also posts a recalculated, unadjusted secondary AUC inhibition comparison for Part 1. Analysis-plan details, multiplicity handling, missing-data methods, and the original sample-size justification are not reported in the registry record.