Effect of Calcium 500 mg and Vitamin D3 1000 IU Chewable Tablet on Intestinal Calcium Absorption: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Calcium 500 mg and Vitamin D3 1000 IU Chewable Tablet on Intestinal Calcium Absorption (NCT02338713), a na phase 1 study. The primary outcome is PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone.

2. Clinical Question

The central statistical question is whether the measured short-term parathyroid hormone profile differed between the water and Calcichew D3 reporting periods. The endpoint is a summary of repeated serum measurements over a defined post-dose interval, rather than a single concentration at one time point. The record describes measurements on Day 3 for the noncarbonated-water reporting group and Day 6 for the Calcichew D3 reporting group, with measurements before dosing and at multiple post-dose time points through 6 hours.

Because treatment was given in a single sequence, the comparison is not a randomized contrast. The registry record does not describe an allocation process or masking; it reports allocation as not applicable and masking as none. The posted record therefore supports describing the intended question and design, but not estimating the size, precision, or statistical significance of a treatment-period difference.

3. Trial Design

This was a phase 1, completed, single-group study sponsored by Takeda. It enrolled 27 participants and is identified as a single-sequence, two-period, open-label study. The recorded start was 2015-01, and primary completion was 2015-02. Healthy volunteers were the listed condition.

The treatment sequence began with noncarbonated water, described as 200 mL taken orally once daily on Days 1, 2 and 3 in period 1, which the record calls a dummy treatment period. Calcichew D3 was then described as calcium 500 mg and vitamin D3 1000 IU chewable tablets taken orally once daily, beginning on Day 4. The remaining arm-description text is incomplete in the registry record, so the full dosing schedule should not be inferred from it.

The study is not a randomized comparison. Its water and Calcichew D3 reporting groups represent periods in a stated sequence, rather than independently randomized arms. As a general statistical consideration, sequential period comparisons can be affected by changes over time, order effects, or carryover; whether these were assessed or addressed is not reported in the registry record. Open-label status also means the record does not describe masking of participants or investigators.

The record lists nine outcome measures and identifies parathyroid hormone AUC from 0 to 6 hours as the primary outcome. Other listed outcomes include urinary calcium excretion over 24 hours, parathyroid hormone AUC from 0 to 24 hours, calcium concentration summaries, and participants experiencing at least one treatment-emergent adverse event. The record contains no analysis records for the outcomes. It does not report a protocol, detailed statistical plan, sample-size justification, or interim-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.

Before assignment: Healthy participants were enrolled in this study. Treatment period of study comprised of 2-periods. Participants received noncarbonated water in period 1 (dummy treatment period) and Calcichew D3 in period 2 (study treatment period).

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Pharmacodynamic(PD) serum analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of parathyroid hormone in each treatment period.

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 safety analysis set included all participants who were enrolled and received at least 1 dose of dummy treatment.

6. Primary Endpoint

The registry lists the primary outcome as PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone, measured over Days 3 and 6: pre-dose and at multiple time-points (upto 6 hours) postdose. Day 3 for the noncarbonated water reporting group and Day 6 for the Calcichew D3 reporting group.

The primary endpoint is parathyroid hormone AUC(0-6), measured in hour*picogram per milliliter (hr*pg/mL). It summarizes the serum parathyroid hormone concentration profile from time 0 through 6 hours. The registry record describes measurements before dosing and at multiple time points after dosing on Days 3 and 6. Day 3 corresponds to the noncarbonated-water reporting group, and Day 6 to the Calcichew D3 reporting group.

An area under the curve combines information across the measurement interval. As a general statistical explanation, this can describe overall exposure during a specified period, whereas an individual concentration describes the level at one measurement time. The interpretation depends on the measurement schedule and how the area is estimated; those calculation details are not reported in the registry record.

The listed summary measure is a geometric mean, with geometric coefficient of variation as the dispersion measure. In general, a geometric mean is used for positive measurements whose distribution is better represented on a multiplicative than an additive scale. A geometric coefficient of variation describes relative spread on that scale. These are general interpretations of the named statistics; the registry record does not describe the analysis transformations or estimation procedure.

The endpoint was selected as a pharmacodynamic measure of parathyroid hormone over the post-dose interval. The record explains that AUC(0-6) measures the area under the serum concentration-time curve from 0 to 6 hours. It does not post endpoint estimates, variability values, confidence intervals, or test results, so the magnitude and precision of any period difference cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes the primary outcome with a geometric mean and a geometric coefficient of variation. These summaries characterize the endpoint’s level and relative spread, but they do not by themselves establish a treatment-period contrast. An interpretation of a contrast would require an estimate of the comparison, its uncertainty, and a clear description of the analysis population and method. Those analysis results and details are not reported in the registry record.

What does AUC summarize?

Area under the curve combines measurements taken over time into a summary of the concentration profile during a specified interval. For this endpoint, the interval is 0 to 6 hours and the measured substance is serum parathyroid hormone. In general, AUC can reflect both the magnitude and duration of measured concentrations across the interval. It is not the same as a single post-dose measurement. The registry record does not report the calculation method, handling of missing time points, or any interpolation rules used to estimate the area.

Why use a geometric mean?

General statistical explanation: a geometric mean is suited to positive values when relative changes or multiplicative variation are of interest. The geometric coefficient of variation describes relative dispersion rather than spread in the original measurement units. The choice of these summaries can be relevant when measurements are skewed, but the registry record does not report the observed distribution or explain why this summary was selected. It also does not state whether values were transformed for analysis or how any estimate was calculated.

What would a period comparison need to address?

The recorded design is single-sequence, with water followed by Calcichew D3. In a sequential study, measurements from one participant across periods may be related. General statistical explanation: when participants contribute measurements under more than one condition, an analysis may account for within-participant dependence rather than treat observations as independent. The registry record does not report the model or test used, nor does it say whether the reported analysis was paired, adjusted, or based on another approach.

Order and period are also relevant general considerations for sequential designs. If measurements change over time for reasons other than treatment, a period contrast can combine treatment and time-related influences. Carryover from an earlier period is another general possibility in repeated treatment designs. Whether the study assessed these issues, used a washout, or incorporated period effects into its analysis is not reported in the registry record. The incomplete schedule description does not support assumptions about such procedures.

How should uncertainty be read?

In general, an estimate describes the observed contrast, while a confidence interval communicates the precision of that estimate under the analysis assumptions. A p-value, if reported, addresses compatibility of the data with a specified null hypothesis under a statistical model; it does not quantify the size or importance of an effect. No primary endpoint estimate, confidence interval, or p-value is reported in the registry record. Statistical significance and precision therefore cannot be evaluated from the posted primary outcome information.

The record states that there are no analysis records. This means it does not supply inferential results for the registered outcomes in the analysis record. It does not establish that no analyses were conducted outside the registry. A protocol, analysis plan, model specification, and detailed account of the analysis set are not reported in the registry record.

What do planning illustrations represent?

The sample-size material is described as a planning illustration computed from the observed effect, not as the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the planning quantity is participants per arm for 80% or 90% power; time-to-event calculations use total events. These are planning scenarios, not observed power and not observed participant counts.

General statistical explanation: a planning calculation asks how much information a hypothetical design might need under chosen assumptions. Its answer depends on the assumed effect and variability, as well as the allocation and statistical method. It does not show the probability that the completed study achieved a result, and it cannot substitute for a reported estimate and uncertainty interval. The actual sample-size justification and the assumptions used when the study was planned are not reported in the registry record.

The illustration’s equal-allocation assumption does not describe the registered single-sequence design. Since the primary endpoint effect estimate and its variability are not reported in the registry record, the planning scenarios should not be read as evidence about the observed treatment-period difference. The stated assumptions are informative about the calculation framework only.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary endpoint and lists additional outcomes, including parathyroid hormone AUC from 0 to 24 hours, urinary calcium excretion over 24 hours, calcium concentration and exposure summaries, time to maximum observed calcium concentration, and the number of participants experiencing at least one treatment-emergent adverse event. It reports nine outcome measures in total. No analysis records are present.

When a study examines multiple outcomes or multiple time points, general statistical practice may require consideration of multiplicity: repeated testing can increase the chance of at least one apparently unusual result. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan specifying which comparisons would be confirmatory. It is therefore not possible to determine how any secondary findings would have been interpreted relative to the primary endpoint.

The primary endpoint population is defined as participants who received at least one dose of dummy treatment and had at least one measurable serum parathyroid hormone concentration in each treatment period. The number included in that population is not reported in the registry record. The record does not report missing-data counts, reasons for missing measurements, imputation procedures, or sensitivity analyses. It also does not report whether all enrolled participants completed both periods.

The record identifies enrollment of 27 participants, but this does not establish the number contributing to each endpoint analysis. General statistical explanation: missing measurements can affect both the analyzed population and the interpretation of an estimate, depending on their extent and causes. Without a participant flow, analysis counts, and a stated missing-data method, the impact cannot be assessed. The protocol, statistical analysis plan, and interim-analysis procedures are 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists 27 participants at risk in each reporting group. It records zero participants with serious adverse events in the Noncarbonated Water group and zero in the Calcichew D3 group. For other adverse events, it records zero affected participants in the water group and two in the Calcichew D3 group. These are descriptive counts; the registry record does not report a statistical comparison of the groups.

The design was single-sequence, with water followed by Calcichew D3, rather than a randomized comparison of independent groups. The reporting groups should therefore not be read as like-for-like randomized arms. The same enrollment count appearing in each group does not make the groups independent. The record does not describe a method for comparing adverse-event risk across the periods.

No serious adverse-event terms are listed. Death counts are not reported in the registry record. The listed counts do not provide information about event timing, severity beyond the serious-event classification, duration, or relatedness to treatment. The registry record’s secondary outcome list includes participants experiencing at least one treatment-emergent adverse event, but a separate result for that outcome is not reported in the registry record.

These figures describe what was recorded for the study groups; they do not establish whether the observed count difference is attributable to treatment. With no reported safety analysis or additional event detail, interpretation should remain limited to the posted counts.

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

The registry record establishes that a phase 1, single-sequence, open-label study enrolled 27 healthy volunteers and specified parathyroid hormone AUC(0-6) as its primary endpoint. It also describes a water period followed by a Calcichew D3 period and lists additional pharmacodynamic, calcium-related, and safety outcomes. The record does not report the primary endpoint results or statistical analyses.

As a result, the posted information does not establish the magnitude or direction of a difference in parathyroid hormone AUC between the reporting periods. It does not provide an estimate of precision, such as a confidence interval, or an inferential result such as a p-value. The study purpose described in the registry summary should not be mistaken for a finding that the intended changes occurred.

The design also limits what a period contrast could mean. This was a single sequence rather than randomized allocation to independent treatment groups. General statistical explanation: a comparison across sequential periods can reflect treatment as well as time or order-related factors, and repeated observations from the same participants may require methods that account for their dependence. The registry record does not describe whether or how those considerations were handled.

The adverse-event record reports no serious adverse events in either reporting group and two participants with other adverse events in the Calcichew D3 group, compared with zero in the water group. These are descriptive counts and do not supply a formal comparative safety analysis. Death counts and serious-event terms are not reported.

Planning illustrations based on an observed effect are hypothetical design calculations under stated assumptions. They are not the trial’s observed power, do not replace outcome results, and do not show that the intended effect was detected. The actual sample-size justification is not reported in the registry record. Overall, the record documents the study structure and selected outcomes, but does not provide enough outcome analysis to assess the primary endpoint’s observed effect or precision.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and reporting must be considered alongside an endpoint label. A primary endpoint is specified, and its measurement window and summary statistic are described, but the registry record does not include the endpoint estimate or its statistical analysis. Without those results, readers cannot assess the effect’s direction, size, or precision.

The single-sequence structure is also central. The record identifies water as the dummy-treatment period and Calcichew D3 as the following treatment period. This is not a randomized, like-for-like control comparison. General statistical reasoning highlights that period, order, and within-participant dependence can matter in sequential designs. The registry record does not state how these issues were addressed, so the design description alone cannot answer whether an observed contrast would isolate a treatment effect.

Other notable statistical features are the use of a geometric mean and geometric coefficient of variation for the primary endpoint, and the defined pharmacodynamic analysis population. Both affect how an analysis would be understood, but the number analyzed and the estimation method are not reported. The listed secondary outcomes raise the general question of how multiple outcomes were prioritized or interpreted; multiplicity procedures are not reported.

The safety counts illustrate the difference between descriptive reporting and inference. Counts are available for serious and other adverse events, but the registry record does not provide a comparative analysis or event details sufficient to explain the observed counts. The planning illustrations likewise have a distinct role: they explore hypothetical sample-size requirements under stated assumptions and are not evidence of the study’s results.

Taken together, the record is useful for understanding the intended measurement and design, while its absent analysis results and limited methodological detail constrain statistical interpretation.

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 record does not report results for the primary endpoint. No endpoint estimates, confidence intervals, p-values, or analysis records are reported. This prevents assessment of the observed parathyroid hormone AUC(0-6) values, their variability, and any contrast between the reporting periods.

The design was single-sequence and open-label, and the registry record states that allocation was not applicable. The water period preceded Calcichew D3, so the groups do not form a randomized, like-for-like comparison. The record does not report how period effects, order, within-participant dependence, or possible carryover were handled. The full schedule is also incomplete in the arm description, so unreported details should not be inferred.

Although enrollment was 27, the number meeting the primary endpoint population definition is not reported. Participant completion, missing measurements, reasons for missingness, and any missing-data procedures are not reported. The record also does not describe the model, calculation method for AUC, transformation or estimation procedure, or sensitivity analyses.

Nine outcome measures are listed, but no multiplicity approach or confirmatory hierarchy is reported. The protocol, statistical analysis plan, interim-analysis procedures, and sample-size justification are not reported in the registry record. Safety reporting is limited to participant counts; event details and death counts are not reported. These gaps mean the available record supports a description of the study design and outcomes, but not a comprehensive appraisal of the analyses or their precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Calcium 500 mg and Vitamin D3 1000 IU Chewable Tablet on Intestinal Calcium Absorption — NCT02338713.
• Registry record last updated 2017-06-16; status last verified 2017-04.
• Results first posted 2017-06-16.
• 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

This completed phase 1 study enrolled 27 healthy volunteers and was sponsored by Takeda. The registry record describes a single-sequence, two-period, open-label design, with noncarbonated water followed by Calcichew D3. The primary endpoint was parathyroid hormone AUC(0-6), summarized as a geometric mean with geometric coefficient of variation.

The primary endpoint analysis population is defined in the record, but its analyzed participant count is not reported. No outcome analysis records or primary endpoint results are reported. The record lists nine outcome measures, including additional parathyroid hormone, urinary calcium, calcium concentration, and safety measures. It records zero serious adverse events in each group and other adverse events in zero water-period participants and two Calcichew D3-period participants. The protocol, detailed analysis methods, missing-data procedures, and sample-size justification are not reported in the registry record.