Dose Ranging Study - Macroflux Parathyroid Hormone (PTH) in Postmenopausal Women With Osteoporosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Ranging Study - Macroflux Parathyroid Hormone (PTH) in Postmenopausal Women With Osteoporosis (NCT00489918), a randomized phase 2 study. The primary outcome is Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24.

2. Clinical Question

3. Trial Design

This completed phase 2 study is described as a multicenter dose-ranging study of Macroflux parathyroid hormone in women with osteoporosis. The registry lists 165 enrolled participants. It describes the design as randomized, quadruple-masked, and parallel-group, with five arms: Macroflux placebo, Macroflux 20 mcg, Macroflux 30 mcg, Macroflux 40 mcg, and FORTEO 20 mcg injection. The record does not report the allocation ratio or the details of how randomization and masking were implemented.

The listed study period runs from 2007-06 to primary completion in 2008-04. The registry status is completed. The primary endpoint is percent change in lumbar spine bone mineral density from baseline to Week 24. The stated primary population is the Intent to treat (ITT)/Safety Population. The record also lists secondary outcomes covering lumbar spine bone mineral density at Week 12, and total hip and femoral neck bone mineral density at Week 24. Four secondary outcomes are posted.

The listed arm descriptions identify patch interventions for the Macroflux groups and an injection for FORTEO. No direct comparison between active patch doses is included among the displayed primary contrasts; each listed contrast uses Macroflux placebo as its reference. The registry record does not report the original design assumptions, the planned allocation ratio, detailed eligibility criteria, or the rationale for the selected trial size. It also does not report how participants were assigned to analysis sets beyond naming the ITT/Safety Population for the primary outcome.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT)/Safety 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: Postmenopausal women with osteoporosis

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24, measured over 24 weeks.

The primary endpoint is the mean percent change in lumbar spine bone mineral density from baseline to Week 24. Bone mineral density is a continuous measurement of mineral content in bone, and percent change expresses the follow-up measurement relative to the participant’s starting value. In general, a continuous change measure can describe both the direction and average size of change over a specified period, while variation among participants is represented separately by the standard deviation.

Lumbar spine bone mineral density is one measure of skeletal status. It is used in clinical research because it can be measured at baseline and follow-up and summarized across participants. The endpoint in this trial is a measurement outcome rather than a direct measure of fractures, symptoms, or day-to-day functioning. A difference in average bone mineral density change therefore answers a narrower question than whether participants experienced differences in those other outcomes.

The registry identifies the primary population as the Intent to treat (ITT)/Safety Population and gives the timeframe as 24 weeks. It reports arm means and standard deviations, but not confidence limits for those arm means. The posted mean differences and confidence intervals compare each active arm with Macroflux placebo and are unadjusted recalculations from the reported summaries, rather than registry-reported inferential analyses.

7. Results Posted in the Registry

• Macroflux® 20 mcg: mean 2.96 versus -0.33 on control; difference 3.29 (95% CI 1.62 to 4.96), standardized effect d = 0.94; z-test p = <0.001.
• Macroflux® 30 mcg: mean 3.47 versus -0.33 on control; difference 3.80 (95% CI 2.09 to 5.51), standardized effect d = 1.08; z-test p = <0.001.
• Macroflux® 40 mcg: mean 4.97 versus -0.33 on control; difference 5.30 (95% CI 3.46 to 7.14), standardized effect d = 1.39; z-test p = <0.001.
• FORTEO®: mean 3.55 versus -0.33 on control; difference 3.88 (95% CI 2.14 to 5.62), standardized effect d = 1.08; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Macroflux® 20 mcg: mean 1.55 versus 0.97 on control; difference 0.58 (95% CI -0.85 to 2.01), standardized effect d = 0.19; z-test p = 0.427.
  • Macroflux® 30 mcg: mean 2.04 versus 0.97 on control; difference 1.07 (95% CI -0.53 to 2.67), standardized effect d = 0.32; z-test p = 0.190.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Macroflux® 20 mcg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Macroflux® 30 mcg and the control. The interval gives the range of effects that remain compatible with the data.

Absolute Change in Lumbar Spine BMD: Baseline to Week 12

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Macroflux® 20 mcg: mean 0.01 versus 0.01 on control; difference 0.00 (95% CI -0.01 to 0.01), standardized effect d = 0.19; z-test p = 0.444.
  • Macroflux® 30 mcg: mean 0.01 versus 0.01 on control; difference 0.01 (95% CI -0.00 to 0.02), standardized effect d = 0.30; z-test p = 0.232.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Macroflux® 20 mcg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Macroflux® 30 mcg and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Macroflux® 20 mcg: mean 0.14 versus -0.63 on control; difference 0.77 (95% CI -0.19 to 1.73), standardized effect d = 0.38; z-test p = 0.115.
  • Macroflux® 30 mcg: mean 0.55 versus -0.63 on control; difference 1.19 (95% CI 0.13 to 2.25), standardized effect d = 0.55; z-test p = 0.028.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Macroflux® 20 mcg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Macroflux® 30 mcg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the secondary outcomes, the broad descriptive pattern is that the patch arms tend to show greater mean change than placebo, while the pattern is not identical across measurement sites and timeframes. The lumbar spine outcomes are assessed at Week 12, while the total hip and femoral neck outcomes are assessed at Week 24. The posted values therefore describe different outcomes and, for some measures, different timepoints; they should not be treated as interchangeable repetitions of the primary endpoint.

The secondary summaries add context to the primary lumbar spine result by showing how average changes look at an earlier lumbar spine assessment and at other skeletal sites. They do not replace the primary endpoint or establish that patterns across locations are consistent. A result at one site or timepoint need not imply a corresponding result at another site or timepoint. The secondary data are descriptive unless supported by an appropriate analysis that addresses uncertainty and the set of outcomes considered.

Unadjusted secondary comparisons carry less weight for confirmatory interpretation because the registry record lists multiple outcomes and comparisons but does not report a multiplicity procedure or an analysis hierarchy. When multiple tests are examined, an isolated small p-value can occur by chance more often than when only one prespecified test is considered. The secondary contrast calculations are unadjusted, and the registry record does not report sponsor analyses for them. They can be read as exploratory context, not as a definitive set of independent confirmations of the primary finding.

The record also does not report how missing observations were handled for these outcomes or whether all participants contributed to every endpoint. These reporting gaps limit interpretation of how the secondary summaries relate to the full randomized groups. The overall pattern is useful for describing consistency and variation across the recorded measurements, but the available registry information does not support a stronger claim about a unified response across outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12
• Absolute Change in Lumbar Spine BMD: Baseline to Week 12
• Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24
• Percent Change in Femoral Neck BMD: Baseline to Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

What do the arm means describe?

The primary outcome is a continuous measure, summarized as a mean and standard deviation for each arm. A mean describes the average percent change in lumbar spine bone mineral density from baseline to Week 24. A standard deviation describes the spread of participant-level changes around that average. It is not the uncertainty in the mean itself: uncertainty in a mean or contrast also depends on the number of observations and the variation in those observations.

The posted primary arm summaries report the mean and standard deviation for Macroflux placebo, each of the three patch doses, and FORTEO. The group sizes are also reported. The registry does not give confidence intervals around the individual arm means. Reading the means together with standard deviations helps distinguish the average change from the variability among participants, but neither alone captures all sources of uncertainty about a comparison.

How are the contrasts formed?

The posted primary contrasts compare each active arm with Macroflux placebo. A mean difference is the active-arm mean minus the placebo-arm mean. The registry record does not list sponsor-reported inferential analyses; the contrasts, confidence intervals, and p-values are unadjusted recalculations from the posted summary statistics. The calculations use the stated group sizes and standard deviations and treat each comparison as an unadjusted two-group comparison.

A confidence interval gives a range of values compatible with the estimate under the assumptions of the calculation. A p-value addresses how compatible the observed contrast is with a null hypothesis of no mean difference under the statistical model. Neither statistic describes the probability that a particular hypothesis is true. Because the contrasts are unadjusted, their p-values and intervals do not account for the set of comparisons across multiple active arms and outcomes.

What does the standard deviation contribute?

In a continuous outcome, variation affects how precisely the mean difference can be estimated. Greater variation makes it harder to distinguish an arm difference from sampling fluctuation when sample sizes are otherwise similar. This is why effect estimates should be considered alongside both the observed variability and group sizes. The primary summaries show standard deviations in the approximate range of three to four percentage points, but the record does not describe any model adjustment for baseline values or other participant characteristics.

The comparisons use a pooled standard deviation in the recalculation, combining information about spread across the two arms being compared. This is a conventional approach to a two-group mean comparison when the calculation treats the groups as having a common variance. The registry record does not report whether this approach was part of the trial’s original statistical plan. Nor does it report adjusted analyses that might account for stratification, repeated measures, covariates, or other design features.

What does an unadjusted result leave out?

Unadjusted means that each contrast is evaluated without correcting for the fact that several contrasts or outcomes are considered together. When many tests are examined, the chance of seeing at least one apparently unusual result can increase. Multiplicity procedures can address that issue, but the registry record does not report whether any such procedure was planned or used. The displayed primary comparisons should therefore be read as separate unadjusted calculations, not as a familywise-confirmatory analysis.

The registry lists five outcome measures, including the primary endpoint and four secondary outcomes, and reports no analyses in its analysis listing. It does not give an analysis plan, prespecified hypotheses for individual contrasts, or a hierarchy for interpreting endpoints. The record also does not report details of missing-data handling, including whether the primary summaries used observed cases, imputation, or another approach. The stated population label alone does not specify how missing observations were treated.

What can the calculations establish?

These methods describe comparisons of average changes in the posted outcome summaries. They do not estimate effects on unreported outcomes, identify the mechanism behind any difference, or establish that an observed difference is clinically important. The recalculations are useful for interpreting the posted summary data, but they are not a substitute for a documented sponsor analysis. The registry record does not report the trial’s own statistical plan, sample-size justification, interim analysis procedures, or detailed analysis populations beyond the primary population label.

11. Confidence Intervals and Precision

The primary mean-difference estimates have confidence intervals that help show how precisely each placebo comparison is estimated. For Macroflux 20 mcg versus placebo, the estimated difference is 3.29, with a 95% confidence interval from 1.616 to 4.964. For Macroflux 30 mcg versus placebo, the estimate is 3.8, with a 95% confidence interval from 2.087 to 5.513. For Macroflux 40 mcg versus placebo, the estimate is 5.3, with a 95% confidence interval from 3.464 to 7.136. For FORTEO versus placebo, the estimate is 3.88, with a 95% confidence interval from 2.143 to 5.617.

A confidence interval is a range generated by a statistical procedure to represent uncertainty in an estimate. In general, narrower intervals indicate greater precision and wider intervals indicate less precision, given the assumptions of the method. Each interval above is wholly on the positive side of zero. That is consistent with the unadjusted p-values reported for these comparisons, each <0.001. These intervals do not account for multiplicity, because the recalculations are unadjusted.

The intervals are not registry-reported sponsor analyses; they are recalculated from the posted arm summaries. Arm means themselves do not have reported confidence limits in the registry record. The intervals also do not resolve uncertainty about missing data, the analysis plan, or how well this trial’s results apply beyond its studied population and timeframe. Precision of a mean difference is not the same as certainty about clinical importance or about other outcomes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are expressed as participants per arm for 80% power and participants per arm for 90% power. They are not totals across arms. The planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers an effect equal to the observed effect and smaller fractions of that effect. The registry record does not report the original design’s sample-size assumptions, so these figures describe an illustration based on the posted result, not the trial’s original design.

In plain language, the 80% power column gives the approximate participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect if that effect were the true one and the planning assumptions held. The 90% power column uses a higher target chance of detection, which generally requires more participants. The illustrations are recalculated from the observed effect and should not be read as a measure of how likely the completed trial was to detect an effect.

Each planning row uses a different assumed effect size: the observed effect, 75% of the observed effect, or 50% of the observed effect. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm to achieve the same target power. These planning counts are not observed power; they are hypothetical sample-size illustrations under the stated assumptions. The original protocol’s sample-size justification is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.290; pooled standard deviation σ = 3.496.
2. n = 2 × (1.96 + 0.842)² × 3.496² / 3.290² = 17.7, rounded up to 18 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 3.29                      # observed difference in means
sigma <- 3.49605460263643                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(489918)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 75% of observed effect: n per arm = 32 (80% power), 43 (90% power)
 50% of observed effect: n per arm = 71 (80% power), 95 (90% power)
power.t.test: 18.7 
Simulated power at n = 18 per arm: 0.780 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures: the primary lumbar spine percent change at Week 24 and four secondary outcomes. The primary results include four active-versus-placebo comparisons. The record does not report a prespecified testing hierarchy, an adjustment for multiple comparisons, or another strategy for controlling the overall type I error rate. The p-values attached to the recalculated comparisons are unadjusted. As a result, they should not be interpreted as multiplicity-controlled evidence across all arms and outcomes.

The registry lists no reported analyses. This means the record does not document a sponsor analysis result or a statistical analysis plan that would clarify which comparisons were intended to be confirmatory, how endpoints were prioritized, or whether any adjustment was used. The absence of that information does not establish that no analysis plan existed; its contents are not reported in the registry record.

The primary population is named as the Intent to treat (ITT)/Safety Population, but the record does not explain how that population was defined or how participants with missing measurements were handled. It does not report the number of participants with evaluable primary outcome data by arm beyond the sizes attached to the posted summaries, nor does it describe the reasons for any missing data, imputation, or sensitivity analyses. Thus, it is not possible to assess from the registry record whether missingness could have affected the reported comparisons.

The record also does not report whether there were interim analyses, stopping rules, or changes to the analysis plan. These omissions matter because endpoint selection, repeated testing, and missing-data decisions can affect how much weight to place on nominal p-values. The recalculated comparisons remain useful descriptions of the posted arm summaries, but they do not resolve these design and analysis uncertainties.

15. 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: subdural hematoma (3.0%), dehydration (2.9%).

The registry reports serious adverse events among participants at risk in each arm. The counts are 1 in the Macroflux placebo arm, 1 in the 20 mcg arm, and 0 in each of the 30 mcg, 40 mcg, and FORTEO arms. These are counts of participants reported as affected by a serious adverse event, not a comparative statistical analysis. The registry does not report a safety comparison or confidence intervals for these counts.

For other adverse events, the reported affected counts are 29 for placebo, 32 for Macroflux 20 mcg, 31 for Macroflux 30 mcg, 30 for Macroflux 40 mcg, and 23 for FORTEO. The counts should be interpreted in relation to the at-risk group sizes shown in the safety record and do not describe event severity or type by themselves. The listed serious adverse event terms include Subdural hematoma at 3.0% and dehydration at 2.9%; the record does not specify their arm-specific distribution in the information. Death counts are not reported in the registry record.

Small group sizes and limited event counts make these summaries descriptive. They do not establish differences in safety between arms, and the registry does not report a statistical safety analysis. The counts also do not provide a complete account of event timing, duration, or causal attribution.

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

The results describe average changes in lumbar spine bone mineral density over 24 weeks among participants in this randomized phase 2 study. The posted arm means are higher in each active arm than in the Macroflux placebo arm, and the unadjusted recalculated mean-difference intervals are above zero. The estimates give a quantitative account of the observed contrast and its statistical uncertainty under the calculation assumptions.

That description is narrower than a claim about whether a treatment works. The primary endpoint is a bone mineral density measurement, not a direct measure of fractures, symptoms, function, or longer-term outcomes. The registry record does not report those outcomes as primary results. Nor do the posted primary contrasts establish differences among the patch doses or between a patch dose and FORTEO, because the listed contrasts use placebo as the comparator.

The comparisons are unadjusted recalculations, and the registry record does not report multiplicity handling, missing-data methods, or the original analysis plan. These limitations affect how the nominal p-values should be read. Confidence intervals communicate uncertainty under a particular statistical calculation, but they do not account for unreported analysis choices or establish clinical importance.

The study is a phase 2 dose-ranging trial in postmenopausal women with osteoporosis. Its results are tied to the enrolled study population, the listed interventions, and the 24-week primary timeframe. The registry information does not establish how well the estimates generalize to other populations, settings, or durations. The reported safety counts likewise do not provide a comparative safety analysis or a complete account of adverse-event timing and attribution.

In short, the record supports a description of the observed group summaries and unadjusted placebo comparisons for the specified bone mineral density outcome. It does not, by itself, settle questions about clinical outcomes, longer-term effects, comparative performance among active arms, or the findings of an unreported sponsor analysis.

17. Why This Trial Matters Statistically

This trial illustrates why a dose-ranging study is not interpreted solely by looking at whether the highest reported mean is numerically largest. The primary outcome is continuous, and each arm has both a mean and a standard deviation. The mean describes average change; the standard deviation conveys variability among participants. Contrasts with placebo and their confidence intervals provide a more direct account of estimated differences and precision than a visual ranking of means alone.

The design also includes several active comparisons and multiple outcomes. That makes the distinction between an unadjusted comparison and a multiplicity-controlled analysis important. A nominal p-value may describe one contrast, but without a reported testing strategy it cannot be treated as a fully documented confirmatory result across all endpoints and arms. The registry’s lack of listed analyses and statistical-plan details is therefore relevant to interpretation, not merely a reporting technicality.

The sample-size illustrations show another statistical issue: the number of participants needed depends on the effect size a study aims to detect. Planning around the observed effect can yield a different requirement than planning for a smaller effect. The figures are conditional illustrations rather than evidence of the completed study’s power, and the original design justification is not reported.

Finally, the primary endpoint is a biomarker-style measurement with a defined timeframe. Statistical evidence about this measurement does not automatically answer questions about other clinical outcomes. Separating the measured endpoint, its uncertainty, the analysis procedures, and the broader interpretation is essential to reading this record carefully.

18. 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 registry record leaves important design and analysis details unreported. It does not provide the original sample-size justification, allocation ratio, detailed eligibility criteria, or a complete statistical analysis plan. It also does not describe the randomization procedure or explain how quadruple masking was implemented. These omissions limit assessment of design choices beyond the broad randomized, parallel-group description.

For the primary results, the record presents arm summaries but no sponsor-reported inferential analyses. The mean differences, confidence intervals, and p-values are unadjusted recalculations from those summaries. The record does not report whether the original analysis used covariate adjustment, a particular missing-data method, or a multiplicity procedure. It also does not explain the operational definition of the ITT/Safety Population.

The primary timeframe is 24 weeks, and the endpoint is lumbar spine bone mineral density change. This outcome and follow-up period do not provide direct information about all clinical outcomes or longer-term effects. Secondary measures cover different bone sites and timepoints, but the registry does not report a hierarchy or adjusted secondary analyses. The available outcome summaries therefore do not establish a single confirmatory pattern across all measurements.

The safety information is limited to affected counts and listed serious event terms. The registry does not report comparative safety tests, event timing, detailed attribution, or deaths. The small group sizes also mean that uncommon events may not be well characterized. These limitations should be considered when interpreting the safety summaries, without treating the counts as evidence for or against a difference between arms.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Dose Ranging Study - Macroflux Parathyroid Hormone (PTH) in Postmenopausal Women With Osteoporosis — NCT00489918.
• Registry record last updated 2018-07-31; status last verified 2018-07.
• Results first posted 2018-07-31.
• 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.

22. Record Summary

NCT00489918 is a completed randomized, quadruple-masked, parallel-group phase 2 dose-ranging study sponsored by Zosano Pharma Corporation. It enrolled 165 participants and studied Macroflux PTH patches at 20 mcg, 30 mcg, and 40 mcg, alongside a Macroflux placebo patch and FORTEO 20 mcg injection, in postmenopausal women with osteoporosis.

The primary endpoint was mean percent change in lumbar spine bone mineral density from baseline to Week 24 in the stated ITT/Safety Population. The posted group means were higher in each active arm than in the placebo arm. The associated mean differences, confidence intervals, and p-values are unadjusted recalculations from the posted summaries; the registry record lists no reported analyses. It does not report the original statistical plan, multiplicity handling, missing-data methods, or sample-size justification.