A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism (NCT02910466), a na phase 4 study. The primary outcome is Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6.

2. Clinical Question

The study asks how albumin-corrected serum calcium changes by Month 6 during extended use of rhPTH(1-84) in participants with hypoparathyroidism. It is a single-group study: participants received rhPTH(1-84), with no concurrent control group described. The registry identifies the primary measure as change from baseline in albumin-corrected serum calcium concentration, in mmol/L.

The study is framed as an extension of prior treatment experience. Its brief description says members of the AAAE0544 core-study group had taken rhPTH(1-84) for up to 11 years, and that the extension was intended to add knowledge about long-term safety and effectiveness. That context does not create a control comparison: the reported design remains single-group and open-label. The primary endpoint therefore describes change over time during treatment, rather than an estimated difference in outcomes between treatment strategies.

3. Trial Design

This is a Phase 4, open-label, single-center, single-group clinical study of rhPTH(1-84) in hypoparathyroidism. The registry lists the study as completed, with an enrollment of 39. It records no allocation to comparative arms and no masking. There is no like-for-like control comparison in the design; changes are assessed against baseline within the treated group.

The intervention is daily subcutaneous rhPTH(1-84), injected into the thigh using a multidose pen injector. The listed dose levels are 25, 50, 75, and 100 micrograms. The dose description says it is individualized based on albumin-corrected serum calcium and 24-hour urinary calcium excretion. The planned treatment duration is 36 months. The remaining text of the arm description is incomplete in the registry record, so no further dose-management detail can be stated.

The study’s brief description places the extension in the context of participants from the AAAE0544 core study, who had used rhPTH(1-84) for up to 11 years. It describes the purpose as extending experience and gathering long-term safety and effectiveness information. The primary outcome is change in albumin-corrected serum calcium at Month 6. Other listed outcomes include calcium levels at later visits, urinary calcium, serum phosphate, supplement doses, and symptom and quality-of-life measures.

The registry defines the primary-outcome baseline as the last available pre-dose value in SHP634-402. It also explains that the safety population includes enrolled participants who received at least one dose, regardless of whether they came from SHP634-402 or the AAAE0544 core study; for an outcome, the overall number analyzed refers to participants evaluable for that measure. The registry record does not report the numerical primary outcome result, the number evaluable for it, or additional details needed to reconstruct the analysis.

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: A total of 39 participants were enrolled in the study who were treated in the core AAAE0544 (NCT01199614) study, out of which, 36 participants received treatment in this study. This study reports the additional data only for the current study (SHP634-402) which is on long term safety and efficacy of over 36 months of exposure to rhPTH(1-84), and the results for core study AAAE0544 (NCT01199614) will be posted separately, as planned.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome 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: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6, measured over Baseline (402), Month 6.

The primary endpoint is change from baseline in albumin-corrected serum calcium concentration at Month 6. It is a continuous measure reported in millimoles per liter. The registry identifies the summary measure as the mean and the dispersion measure as the standard deviation. Baseline is specifically defined as the last available pre-dose value in SHP634-402, rather than an unspecified visit or a value derived from all prior observations.

As a general statistical description, a change endpoint expresses how a measured value differs from its reference value for each participant, and a group mean summarizes the average direction and size of those changes. The standard deviation describes how dispersed individual values are around that average. Neither statistic alone shows the full distribution of participant-level changes.

Albumin-corrected serum calcium is the biochemical measure selected by the registry as the primary outcome for this study. The endpoint focuses on a defined time point during extended use, allowing the study to describe the group’s calcium change relative to the stated baseline. In a single-group study, that change is descriptive of the observed course in the enrolled group; it is not, by itself, a treatment-versus-control effect.

The registry record does not report the Month 6 mean change, its standard deviation, a confidence interval, a test statistic, a p-value, or the number evaluable for the endpoint. Consequently, the direction, magnitude, and precision of the observed primary outcome cannot be assessed from the recorded information. No conclusion about how large or consistent the change was can be drawn from the endpoint definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous variable: change in albumin-corrected serum calcium concentration. For a continuous measure, a mean summarizes the group’s average, while a standard deviation describes variation among observed values. These are complementary summaries. The mean conveys the average change, and the standard deviation indicates whether individual values lie relatively close to that average or are more spread out. Neither should be interpreted as the result for every participant.

A change-from-baseline analysis first uses a defined reference measurement, then evaluates how the measure differs at a later assessment. Here, the registry defines baseline as the last available pre-dose value in SHP634-402, and identifies Month 6 as the primary follow-up time. This definition matters because a change depends on the selected baseline. The record does not report whether the primary analysis used any further adjustment, transformation, or model, so those details cannot be inferred.

A confidence interval, if reported, would express the uncertainty around an estimated group mean change under the assumptions of the analysis. In general, a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. It would not show the range of all individual participant outcomes; the standard deviation is a more direct summary of participant-level spread. No confidence interval is reported for the primary outcome in the registry record, so its precision cannot be evaluated from the available result information.

A p-value, if reported, would relate the observed data to a specified statistical null model. It would not measure the size or importance of the change, nor would it establish causation. The registry record does not report a primary-endpoint p-value or identify a statistical test for that endpoint. The outcome description alone does not reveal whether statistical significance was assessed or what decision rule might have been used.

The design is single-group rather than randomized and comparative. In a randomized comparison, an estimated difference between groups can be used to assess relative outcomes while relying on the trial’s design and analysis assumptions. In a single-group study, a change from baseline instead describes an observed trajectory in the enrolled group. As a general matter, this type of estimate cannot separate treatment-associated change from other influences as securely as a concurrent randomized comparison can. No treatment-versus-control estimate is available in this registry record.

Repeated measures are listed among the secondary outcomes, with assessments at several times extending to Month 36 or end of treatment. General methods for repeated measurements account for the fact that observations from the same participant are related rather than independent. Different methods may also make different assumptions about incomplete follow-up. The registry record does not report the method used for these repeated assessments, any correlation structure, or the assumptions made about missing measurements.

Multiplicity is a general concern when many outcomes or time points are examined: the more statistical tests considered, the greater the chance of at least one apparently unusual result under a collection of null hypotheses. Methods such as prespecifying a primary endpoint or adjusting for multiple tests can address particular multiplicity questions, but the appropriate approach depends on the analysis plan. The registry record names one primary outcome and numerous secondary outcomes, but does not report a multiplicity adjustment or a testing hierarchy. The listed outcomes therefore cannot be treated as though a specific multiplicity procedure was used.

The registry’s analysis-population description requires care. It defines the safety population as enrolled participants who received at least one dose, regardless of whether they were in SHP634-402 or the AAAE0544 core study. It further states that the overall number analyzed for an outcome refers to participants evaluable for that outcome. Thus, the safety population definition and the endpoint-specific evaluable group are not interchangeable. The primary outcome’s actual analysis count is not reported in the registry record.

The adverse-event figures are counts and percentages from a safety listing, not an estimate of comparative risk. General safety interpretation distinguishes the number of participants at risk from the number reported as affected and distinguishes serious adverse events from other adverse events. Event listings can describe what was reported during observation, but without a control group and additional context they do not establish causality. The registry supplies no comparative safety estimate.

The record also describes sample-size calculations as planning illustrations based on the observed effect, rather than the trial’s own design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are prospective planning scenarios, not observed power and not evidence that the completed study was designed with those assumptions. The numerical planning outputs and the fraction used are not reported in the registry record, and no additional calculation can be reconstructed from the available information.

In short, the registry specifies endpoint type, summary statistic, baseline definition, and broad design features, but does not document enough analysis detail to reproduce the primary result. The model, missing-data approach, multiplicity procedure, confidence interval method, and primary test are not reported in the registry record. These omissions limit evaluation of both the precision of the endpoint estimate and the robustness of any interpretation.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("rhPTH(1-84)")
n   <- c(23)
m   <- c(-0.005)
sp  <- c(0.1546)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  rhPTH(1-84)  23  -0.005  0.155  -0.072  0.062

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and multiple secondary outcomes. Secondary measures include albumin-corrected serum calcium status, urinary calcium excretion, serum phosphate, calcium and active vitamin D supplement doses, symptom diary scores, cognitive function, and fatigue. Several are listed at repeated visits through Month 36 or end of treatment. The registry record does not report whether tests across these outcomes or time points were adjusted for multiplicity, whether a testing hierarchy was used, or whether some outcomes were intended to be descriptive.

Missing-data handling is also not reported in the registry record. It does not state how unavailable Month 6 measurements were treated, whether participants with incomplete follow-up were included in a model, or what assumptions were made about missingness. The outcome population description says that the overall number analyzed refers to participants evaluable for the outcome, but does not provide the primary endpoint’s evaluable count. It is therefore not possible to determine from the record whether all enrolled participants contributed to the primary estimate or how incomplete data affected it.

The registry defines the safety population as enrolled participants who received at least one dose, including those from SHP634-402 or the AAAE0544 core study. This definition differs from the endpoint-specific evaluable population, and the two should not be conflated. The record does not report a detailed analysis plan or explain whether populations differed across outcomes.

Because there is no reported endpoint estimate or missing-data method, the available record cannot support an assessment of how incomplete observations might affect the mean change. General statistical practice recognizes that conclusions can depend on assumptions about unobserved values, but the assumptions used in this study are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: hypocalcaemia (7.7%), angina pectoris (2.6%), hiatus hernia (2.6%), cholecystitis (2.6%), clostridium difficile colitis (2.6%).

The registry’s serious adverse event listing for rhPTH(1-84) reports 39 participants at risk and 6 affected. For other adverse events, it reports 39 at risk and 34 affected. The listed number of deaths is zero. These are separate registry summaries; the figures should not be combined or treated as mutually exclusive categories without further information.

The serious-event terms listed with percentages are hypocalcaemia at 7.7%, angina pectoris at 2.6%, hiatus hernia at 2.6%, cholecystitis at 2.6%, Clostridium difficile colitis at 2.6%, and gastroenteritis at 2.6%. These entries describe reported events in the registry record. They do not show whether an event was judged related to treatment, when it occurred, or whether it led to a change in study treatment. Such details are not reported in the registry record.

As a general statistical point, adverse-event counts describe observed reporting during a study and do not establish that treatment caused an event. A controlled comparison can help estimate differences in reported event frequency, but this study is single-group and provides no concurrent control comparison. The safety figures should therefore be read descriptively, not as comparative estimates of risk or proof of causation.

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

The record establishes that this completed Phase 4 study examined extended rhPTH(1-84) use in hypoparathyroidism in an open-label, single-center, single-group design. It defines the primary endpoint as mean change from a specified baseline in albumin-corrected serum calcium at Month 6 and identifies the standard deviation as the measure of dispersion. These details clarify what the primary outcome was intended to summarize.

The record does not report the numerical primary result. It therefore does not show whether the mean change was positive, negative, or near zero, how large it was, how much participant-level variation there was, or how precisely the mean was estimated. The absence of a numerical result is not evidence that there was no change; it means the result is not reported in the registry record.

Even if a within-group change were available, the design would support description of change over time in the enrolled group, not a clean estimate of the difference that would have occurred under another treatment strategy. There is no randomized or concurrent control group. Open-label, single-center conduct also limits what can be inferred beyond the recorded study group. These are design considerations, not claims about the direction or quality of any observed outcome.

The study description places the work in the context of long-term experience among people in the AAAE0544 core study, whose participants had taken rhPTH(1-84) for up to 11 years. That context explains the extension’s stated purpose, but does not replace the need for reported outcome estimates, analysis details, and appropriate comparisons when interpreting efficacy or safety.

The adverse-event information supplies descriptive counts and selected serious-event percentages, including zero deaths. Those entries do not establish causality and do not offer a comparative safety estimate. The registry record also does not report the missing-data, multiplicity, or detailed analysis methods needed to evaluate the robustness of endpoint findings.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between an extended-use study and a comparative treatment trial. Its single-group design can describe measurements over time in participants receiving rhPTH(1-84), but it does not provide a concurrent estimate of what would have happened under a different treatment condition. That distinction is central when interpreting a change-from-baseline endpoint.

The endpoint is also precisely defined in some important respects: it is a mean change in albumin-corrected serum calcium at Month 6, expressed in mmol/L, with standard deviation as the dispersion measure. The baseline is the last available pre-dose value in SHP634-402. Those definitions help make clear which measure and reference are intended. Yet the registry record does not report the numerical result or its precision, so the endpoint definition cannot answer what change was observed.

The safety-population description further illustrates why analysis denominators matter. The record defines a safety population based on receiving at least one dose and says outcome-specific counts refer to those evaluable for each measure. Enrollment is therefore not necessarily the same as the number contributing to a particular endpoint. The primary endpoint’s evaluable count is not reported in the registry record.

Finally, repeated assessments and numerous secondary outcomes create familiar statistical questions about incomplete observations and multiplicity. Those issues do not invalidate the study, but they affect how results should be read and require analysis details. The registry record does not report the relevant methods. The study is informative as a description of design and stated measurement goals, while the available record leaves the primary result and important analytic context unavailable.

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.

The central limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The mean change, standard deviation, confidence interval, p-value, and number evaluable are absent. Thus, neither magnitude nor precision can be assessed. This is a limitation of the available record, not evidence about what the study observed.

The single-group, open-label, single-center design has no concurrent control group. Any reported within-group change would not by itself distinguish treatment-associated change from other influences over time. The registry also lists no masking and no allocation to a comparative arm. These features constrain causal interpretation and make the study unsuitable for a like-for-like treatment comparison.

The study description refers to participants from an earlier core-study context, and the safety-population definition includes participants from SHP634-402 or the AAAE0544 core study. The record does not give enough detail to establish the precise overlap of participants across studies or the outcome-specific denominators. The 39 enrolled participants should not be assumed to be the number analyzed for every outcome.

Other study-specific details are also absent. The registry record does not report the statistical model or test for the primary endpoint, how missing data were handled, whether multiplicity was addressed, or the full analysis plan. The listed intervention description is truncated after its dose-individualization statement, leaving further dosing-management detail unavailable. The listed safety figures are descriptive and do not provide a concurrent comparative estimate or establish event causation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism — NCT02910466.
• Registry record last updated 2021-07-28; status last verified 2021-07.
• Results first posted 2021-07-28.
• 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

This completed Phase 4 study examined extended use of rhPTH(1-84) in hypoparathyroidism. It was open-label, single-center, and single-group, with 39 enrolled participants. The listed intervention was daily subcutaneous dosing at individualized levels of 25, 50, 75, and 100 micrograms for 36 months.

The primary endpoint was mean change from baseline in albumin-corrected serum calcium at Month 6, with standard deviation as the dispersion measure. Baseline was defined as the last available pre-dose value in SHP634-402. Numerical primary endpoint results and the endpoint-specific analysis count are not reported in the registry record.

The safety listing reports 6 affected by serious adverse events and 34 affected by other adverse events, with 39 at risk for each summary and zero deaths. Selected serious-event terms and percentages are listed in the registry record. As the study has no concurrent control group, these safety figures are descriptive rather than comparative.