This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Randomized, Double-blind, Placebo-controlled, Dose Response Study of AMG 162 (Denosumab) in Japanese Postmenopausal Osteoporotic Subjects (NCT00306189), a randomized phase 2 study. The primary outcome is Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00306189 |
| Phase | Phase 2 |
| Condition | Osteoporosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 212 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
The trial asked whether lumbar spine bone mineral density (BMD) changed over 12 months among Japanese postmenopausal subjects with osteoporosis assigned to denosumab or placebo. The primary endpoint was percent change from baseline at month 12. The randomized, double-blind, placebo-controlled study included three denosumab dose groups: 14 mg, 60 mg, and 100 mg, each administered once every 6 months, and a placebo group.
Population
Japanese postmenopausal subjects with osteoporosis. The primary endpoint analysis population included participants who received at least one dose and had a baseline and at least one post-baseline lumbar spine measurement.
Intervention
Denosumab at 14 mg, 60 mg, or 100 mg, administered subcutaneously once every 6 months, as described in the study objective.
Comparator
Placebo over the 12-month study period.
Primary question
What was the mean percent change from baseline in lumbar spine BMD at month 12 in each dose group and placebo, and how did the sponsor’s reported pairwise comparisons relate each dose group to placebo?
This is a question about a continuous measurement, summarized as a group mean and its 95% confidence interval. The registry record reports three sponsor analyses comparing individual denosumab dose groups with placebo. It does not report a single overall test comparing all four groups or a separate dose-trend analysis. Although safety was also an objective in the study summary, the posted primary endpoint is lumbar spine BMD change; the safety figures are separate descriptive information.
3. Trial Design
This was a randomized, double-blind, parallel-group phase 2 study sponsored by Amgen. The registry record lists 212 participants enrolled. The study is marked completed, with a start date of 2006-01 and primary completion in 2007-06. Its title identifies it as a placebo-controlled dose-response study in Japanese postmenopausal subjects with osteoporosis.
Participants were assigned to one of four groups: placebo, denosumab 14 mg Q6M, denosumab 60 mg Q6M, or denosumab 100 mg Q6M. The study objective describes the denosumab doses as subcutaneous injections once every 6 months, with comparison to placebo over 12 months. The registry identifies the allocation as randomized, masking as double, and model as parallel. It does not describe the randomization sequence, allocation concealment, or whether masking procedures differed across groups; those details are not reported in the registry record.
The primary outcome was lumbar spine BMD percent change from baseline at month 12. The analysis population specified for this outcome consisted of participants who received at least one dose of investigational product and had a baseline and at least one post-baseline lumbar spine measurement. The posted group counts for this outcome are 55 for placebo, 53 for denosumab 14 mg Q6M, 54 for denosumab 60 mg Q6M, and 50 for denosumab 100 mg Q6M. These are outcome analysis counts, not a re-expression of the overall enrollment.
The registry record reports three two-sided t-test analyses, each comparing one denosumab dose group with placebo. It does not describe an overall four-group model, a dose-response model, or a procedure for controlling multiplicity across the pairwise comparisons. The protocol’s sample-size justification and detailed statistical analysis plan are not reported in the registry record.
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
| Stage | Denosumab 14 mg Q6M | Denosumab 60 mg Q6M | Denosumab 100 mg Q6M | Placebo |
|---|---|---|---|---|
| STARTED | 57 | 56 | 56 | 57 |
| COMPLETED | 48 | 50 | 45 | 52 |
| NOT COMPLETED | 9 | 6 | 11 | 5 |
Reasons for not completing this period:
| Reason | Denosumab 14 mg Q6M | Denosumab 60 mg Q6M | Denosumab 100 mg Q6M | Placebo |
|---|---|---|---|---|
| Physician Decision | 0 | 0 | 0 | 1 |
| Adverse Event | 3 | 3 | 2 | 2 |
| Withdrawal by Subject | 4 | 2 | 8 | 1 |
| Ineligibility determined | 1 | 1 | 1 | 1 |
| Other | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All subjects who received \>= 1 dose of investigational product and have a baseline and \>= 1 post baseline measurement at the lumbar spine.
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.
| Characteristic | Unit | Denosumab 14 mg Q6M | Denosumab 60 mg Q6M | Denosumab 100 mg Q6M | Placebo | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 53 | 54 | 50 | 55 | 212 | |
| Age Continuous | Years | 65.9 (SD 7.1) | 65.1 (SD 6.3) | 64.6 (SD 7.1) | 64.6 (SD 7) | 65.1 (SD 6.8) |
| Sex: Female, Male: Female | Participants | 53 | 54 | 50 | 55 | 212 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percent Change from Baseline |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean percent change from baseline in lumbar spine BMD at month 12. BMD is assessed by dual energy X-ray absorptiometry, a measurement method identified in the outcome description. Reporting change as a percentage expresses the follow-up measurement relative to the participant’s baseline measurement, then summarizes those changes as a group mean.
Lumbar spine BMD is used in this trial as a quantitative measure of bone density. A continuous endpoint retains information about the magnitude of individual measurements rather than reducing the outcome to a yes-or-no event. Comparing group means can therefore describe the average change during follow-up in each randomized group. It does not by itself describe the full distribution of participant-level changes or show how many individuals experienced a particular degree of change.
The registry reports a 95% confidence interval for each group mean. A confidence interval communicates the statistical uncertainty around an estimate under the analysis used; it is not a range that guarantees where individual participants’ measurements lie. The sponsor also reports confidence intervals for mean differences between each dose group and placebo. Those intervals address uncertainty in the pairwise contrasts rather than uncertainty around an individual group mean.
The specified analysis population required at least one post-baseline lumbar spine measurement as well as baseline data and at least one dose. Consequently, the endpoint description does not establish how missing follow-up measurements were handled or whether participants without qualifying measurements were included in any other analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted group means for lumbar spine BMD percent change at month 12 are 0.46 for placebo, 5.71 for denosumab 14 mg Q6M, 6.73 for denosumab 60 mg Q6M, and 7.45 for denosumab 100 mg Q6M. The associated 95% confidence intervals are -0.23 to 1.15, 4.76 to 6.65, 5.71 to 7.75, and 6.38 to 8.53, respectively. These are group-level estimates for the endpoint analysis population, not descriptions of each participant’s response.
The sponsor reports three two-sided t-test comparisons against placebo. For denosumab 14 mg, the reported mean difference in final values is 5.25, with a 95% confidence interval from 4.1 to 6.4 and p < 0.001. For 60 mg, the reported difference is 6.27, with a 95% confidence interval from 5.06 to 7.49 and p < 0.001. For 100 mg, the reported difference is 7, with a 95% confidence interval from 5.76 to 8.24 and p < 0.001. The positive reported differences and confidence limits indicate that each sponsor-reported contrast is in the direction of a higher mean final value in its denosumab group than in placebo, under the reported analysis.
A confidence interval describes uncertainty in an estimated group mean or difference under the statistical method; it does not represent the range of participant outcomes. The p-values indicate how incompatible the observed test statistics are with the null hypothesis used by the t-tests, assuming the model’s conditions. They do not measure the size or clinical importance of a difference, and they do not account for all possible sources of bias or uncertainty in the trial.
The endpoint group means increase across the listed denosumab doses, but the registry record does not report a formal trend test or a model estimating a dose-response relationship. The three placebo comparisons should therefore be read as separate reported contrasts, not as proof of a particular dose-response pattern. The registry record also does not report a multiplicity adjustment, so the displayed p-values should not be interpreted as adjusted for the set of comparisons unless such a procedure is documented elsewhere.
These results describe the posted BMD endpoint over the stated follow-up. They do not, by themselves, establish effects on fractures, symptoms, longer-term outcomes, or safety beyond the adverse-event information recorded. Such outcomes and conclusions are not contained in these primary endpoint estimates.
9. Statistical Methods Explained
The primary outcome is continuous: each participant has a numerical percent change in lumbar spine BMD, and the registry summarizes the data with a mean. A mean is the arithmetic center of the observed measurements. It is useful for describing the average change in a group, but it can conceal variation among participants and can be influenced by unusually high or low observations. The registry record does not provide a standard deviation or another measure of participant-level spread for the primary endpoint.
What do the confidence intervals describe?
The group estimates are accompanied by 95% confidence intervals. In general, a confidence interval is a range of values generated by a statistical procedure to express uncertainty about an estimated quantity. For the arm-level results, the quantity is the group mean. For the sponsor’s comparisons, it is the mean difference in final values between a denosumab group and placebo. These are different quantities, so their intervals answer different questions.
The intervals do not show where most individual participants’ changes occurred, nor do they guarantee that the true value lies within the particular interval. Their interpretation depends on the assumptions and analysis used. A narrow interval generally indicates more precision for the estimate than a wider interval, all else being equal; it does not rule out bias from trial conduct, missing data, or analysis choices. The registry identifies the intervals as 95% confidence intervals but does not provide further detail about how the arm-level intervals were constructed.
How should the pairwise tests be read?
The sponsor reports two-sided t-tests comparing final values for each denosumab dose group with placebo. A two-sided test evaluates departures in either direction from the null hypothesis of no difference, rather than testing only for a difference in one prespecified direction. The reported p-values are less than < 0.001 for all three contrasts. In general, a p-value measures the compatibility of the observed data with a specified null model; it is not the probability that the null hypothesis is true, and it is not a measure of clinical importance.
The registry describes the contrast parameter as a mean difference in final values. It does not say that the comparison was adjusted for baseline BMD or other covariates, and it does not provide enough detail to infer such adjustment. The endpoint itself is described as percent change from baseline, while the pairwise test is described as a difference in final values. The analysis specification and the reported group summaries should therefore be distinguished rather than treated as identical quantities.
Why does multiplicity matter?
Three separate dose-versus-placebo tests are reported. When several hypotheses are tested, the chance of obtaining at least one apparently unusual result can be affected by the number of tests and by their dependence. Statistical procedures can control this issue, but no such procedure is described in the registry record. It is also not reported whether these three comparisons were the only planned primary comparisons or whether a testing hierarchy was prespecified. The posted p-values are the reported results; any family-wise or false-discovery adjustment is not reported in the registry record.
What can the planning illustrations tell readers?
Planning illustrations based on an observed effect are not the same as the trial’s original sample-size justification. The record describes the illustrations as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. They are planning examples, not observed power and not evidence that the original study was designed around those assumptions. The trial’s own sample-size justification is not reported in the registry record.
How do distributional features affect a mean analysis?
As a general statistical point, t-test methods rely on the sampling behavior of means and can be sensitive to extreme observations or strong departures from the model assumptions, particularly with limited information about the outcome distribution. Over-dispersion means that variability is greater than assumed by a chosen model; when present, standard errors may be too small if the model does not account for it, making confidence intervals too narrow and tests too optimistic. This is a general concern, not a finding established for this trial. The registry record does not provide participant-level data, distributional diagnostics, or a dispersion assessment.
The registry does not describe the handling of missing outcome data, the imputation method, the approach to participants with incomplete follow-up, or sensitivity analyses. It identifies the endpoint population by measurement availability and treatment exposure, but does not establish whether the sponsor used additional analysis populations. These omissions limit how fully the statistical analysis can be independently evaluated from the record alone.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| t-test, 2 sided | Mean Difference (Final Values) 7 | 5.76 to 8.24 | < 0.001 |
| t-test, 2 sided | Mean Difference (Final Values) 5.25 | 4.1 to 6.4 | < 0.001 |
| t-test, 2 sided | Mean Difference (Final Values) 6.27 | 5.06 to 7.49 | < 0.001 |
The sponsor’s posted analyses are two-sided t-tests of final values, with each denosumab dose group compared separately with placebo. The reported mean differences are 5.25 for 14 mg, 6.27 for 60 mg, and 7 for 100 mg. Their reported 95% confidence intervals are 4.1 to 6.4, 5.06 to 7.49, and 5.76 to 8.24, respectively; each comparison has p < 0.001.
The arm-level endpoint summaries report mean percent change from baseline, while the sponsor describes the comparison parameter as a mean difference in final values. The record does not give enough detail to assume that these are exactly the same analysis quantity or that the contrasts were adjusted for baseline values. The distinction matters when comparing the sponsor’s contrasts with the group-level summaries.
The registry record flags no discrepancy between the sponsor’s reported analyses and the recalculated results. The sponsor’s analysis remains the relevant reported inferential result; the posted group estimates offer complementary descriptive context. The record does not document a multiplicity adjustment, so the reported p-values should be understood as the sponsor’s individual comparison results rather than presumed adjusted values.
11. Multiplicity, Missing Data and Analysis Populations
The endpoint analysis population is defined as participants who received at least one dose of investigational product and had baseline and at least one post-baseline lumbar spine measurement. This definition gives a clear minimum eligibility rule for the posted primary outcome. It does not establish how many randomized participants lacked qualifying measurements, why measurements were unavailable, or how such participants were treated in other analyses. The handling of missing data, including any imputation or sensitivity analysis, is not reported in the registry record.
The registry record reports three dose-versus-placebo comparisons for the primary outcome. It does not state whether the comparisons were prespecified as a family, whether an order of testing was used, or whether p-values or confidence intervals were adjusted for multiplicity. It also does not describe interim analyses, stopping rules, or alpha-spending procedures. Those features are not reported in the registry record, and their absence from the record should not be replaced by assumptions about the protocol.
The outcome entry gives arm-level analysis counts and a mean with a 95% confidence interval. It does not describe an intention-to-treat analysis, a per-protocol analysis, or other analysis populations, beyond the eligibility definition attached to the primary outcome. The distinction between randomized participants, participants who received treatment, and participants with outcome measurements can matter when interpreting a randomized comparison. The record does not permit a complete accounting of how participants moved among those populations.
In general, multiplicity procedures address the increased chance of false-positive findings when multiple hypotheses are tested. Missing-data methods address the uncertainty created when outcomes are not observed for all participants. These are separate issues: a multiplicity adjustment does not resolve missing outcome data, and an imputation method does not correct for multiple comparisons. For this trial, the details needed to assess either issue fully are not reported in the registry record.
The original sample-size justification and detailed statistical analysis plan are also not reported in the registry record. Consequently, the planning illustrations based on observed effects should not be treated as evidence of the original design rationale or as a substitute for prespecified analysis methods.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 4 | 54 | 7.4% |
| Denosumab 14 mg Q6M | 6 | 53 | 11.3% |
| Denosumab 60 mg Q6M | 4 | 54 | 7.4% |
| Denosumab 100 mg Q6M | 2 | 51 | 3.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 49 of 54 |
| Denosumab 14 mg Q6M | 50 of 53 |
| Denosumab 60 mg Q6M | 47 of 54 |
| Denosumab 100 mg Q6M | 48 of 51 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Denosumab 14 mg Q6M | Denosumab 60 mg Q6M | Denosumab 100 mg Q6M |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | 0 of 54 | 0 of 53 | 1 of 54 | 0 of 51 |
| Meniere's disease | Ear and labyrinth disorders | 0 of 54 | 1 of 53 | 0 of 54 | 0 of 51 |
| Colitis | Gastrointestinal disorders | 1 of 54 | 0 of 53 | 0 of 54 | 0 of 51 |
| Colitis ischaemic | Gastrointestinal disorders | 0 of 54 | 1 of 53 | 0 of 54 | 0 of 51 |
| Colonic polyp | Gastrointestinal disorders | 0 of 54 | 1 of 53 | 0 of 54 | 0 of 51 |
| Haemorrhoids | Gastrointestinal disorders | 0 of 54 | 0 of 53 | 0 of 54 | 1 of 51 |
| Intestinal ischaemia | Gastrointestinal disorders | 0 of 54 | 1 of 53 | 0 of 54 | 0 of 51 |
| Hepatitis C | Infections and infestations | 1 of 54 | 0 of 53 | 0 of 54 | 0 of 51 |
| Subdural haematoma | Injury, poisoning and procedural complications | 0 of 54 | 1 of 53 | 0 of 54 | 0 of 51 |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | 1 of 54 | 0 of 53 | 0 of 54 | 0 of 51 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Denosumab 14 mg Q6M | Denosumab 60 mg Q6M | Denosumab 100 mg Q6M |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 21 of 54 | 18 of 53 | 22 of 54 | 22 of 51 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 54 | 3 of 53 | 8 of 54 | 9 of 51 |
| Headache | Nervous system disorders | 5 of 54 | 7 of 53 | 6 of 54 | 3 of 51 |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | 8 of 54 | 4 of 53 | 3 of 54 | 6 of 51 |
| Eczema | Skin and subcutaneous tissue disorders | 5 of 54 | 6 of 53 | 4 of 54 | 6 of 51 |
| Contusion | Injury, poisoning and procedural complications | 8 of 54 | 1 of 53 | 4 of 54 | 1 of 51 |
| Constipation | Gastrointestinal disorders | 1 of 54 | 5 of 53 | 5 of 54 | 2 of 51 |
| Diarrhoea | Gastrointestinal disorders | 4 of 54 | 3 of 53 | 2 of 54 | 3 of 51 |
| Hypoaesthesia | Nervous system disorders | 3 of 54 | 1 of 53 | 2 of 54 | 5 of 51 |
| Malaise | General disorders | 5 of 54 | 2 of 53 | 1 of 54 | 2 of 51 |
Serious events with the highest arm-level rate: haemorrhoids (2.0%), cerebral artery embolism (2.0%), meniere's disease (1.9%), colitis ischaemic (1.9%), colonic polyp (1.9%).
The registry’s serious adverse-event figures are counts of affected participants within the listed at-risk groups. For placebo, 4 of 54 participants were recorded as having a serious adverse event. The corresponding figures are 6 of 53 for denosumab 14 mg Q6M, 4 of 54 for denosumab 60 mg Q6M, and 2 of 51 for denosumab 100 mg Q6M. These are descriptive counts, not adjusted comparisons between randomized groups. No deaths are listed; death information is not reported in the registry record.
The registry also reports other adverse-event counts: 49 of 54 in placebo, 50 of 53 in the 14 mg group, 47 of 54 in the 60 mg group, and 48 of 51 in the 100 mg group. These figures should not be treated as serious adverse events; they belong to a separate adverse-event grouping in the record. The record does not provide a statistical comparison for these counts, nor enough detail to infer timing, duration, severity beyond the recorded categories, or causal relationship to treatment.
Several serious-event terms are listed with percentages: Haemorrhoids, 2.0%; Cerebral artery embolism, 2.0%; Meniere's disease, 1.9%; Colitis ischaemic, 1.9%; Colonic polyp, 1.9%; and Intestinal ischaemia, 1.9%. The registry does not attribute these listed terms to particular treatment groups in the information available for this summary. Small descriptive counts and percentages should be interpreted cautiously and do not, alone, establish a difference in risk between groups.
13. What the Result Does, and Does Not, Mean
The posted data show group mean percent changes in lumbar spine BMD at month 12 and sponsor-reported comparisons of each denosumab dose group with placebo. The group means are 0.46 for placebo, 5.71 for 14 mg, 6.73 for 60 mg, and 7.45 for 100 mg. The sponsor’s reported mean differences are positive for all three dose-versus-placebo comparisons, with 95% confidence intervals that lie above zero and p-values reported as p < 0.001.
These findings describe the measured endpoint in the participants included in the outcome analysis. A group mean does not show the range of individual outcomes, and a confidence interval around a mean or difference is not an interval for individual participants. The trial’s four groups and three pairwise comparisons also do not establish a formal dose-response relationship; no trend test or dose-response model is reported.
The result concerns lumbar spine BMD over the stated 12-month period. It is not, by itself, evidence about fracture outcomes, symptoms, long-term effects, or outcomes that were not posted. Nor do the adverse-event counts establish that an event was caused by treatment or that one group had a reliably different risk. The registry record does not report the detail needed to resolve those questions.
Statistical significance and clinical importance are distinct. The reported p-values indicate the results of the sponsor’s specified tests under their assumptions; they do not measure the importance of the difference for patients. The record does not provide a threshold for a clinically important BMD change, nor does it report a broader benefit-risk analysis. Interpretation should therefore remain tied to the endpoint, population, follow-up, and analyses that are actually recorded.
Randomization and double masking are design features intended to support fair comparison, but they do not eliminate every source of uncertainty. Missing-data handling, multiplicity procedures, and other analysis details are not reported in the registry record. The posted results are informative about the recorded BMD comparisons, while leaving these methodological and broader clinical questions unresolved.
14. Why This Trial Matters Statistically
This trial is statistically informative because it reports a continuous endpoint across placebo and three denosumab dose groups, together with separate dose-versus-placebo estimates. The arm-level means and confidence intervals communicate both the direction of the observed group averages and uncertainty around those averages. The sponsor’s pairwise estimates add a direct inferential comparison for each dose against the control group.
The design also highlights why the analysis question needs to be stated precisely. A collection of pairwise comparisons is not the same as an overall test across all groups or a formal test of dose trend. Although the group means increase across the listed dose levels, the registry record does not report a model or test that evaluates that pattern. A visual ordering of estimates should not be substituted for a prespecified dose-response analysis.
The record illustrates the importance of distinguishing an endpoint summary from a contrast. The outcome is described as percent change from baseline, while the sponsor’s test parameter is described as a mean difference in final values. Without more detail on the analysis specification, readers should avoid assuming that the two summaries have identical definitions or adjustments.
Finally, precision and validity are not interchangeable. Confidence intervals quantify statistical uncertainty under an analysis, but they do not settle questions about missing measurements, multiplicity, generalizability, or unreported design decisions. The registry record supplies enough detail to interpret the posted means and sponsor comparisons at a basic level, while leaving important aspects of the statistical plan undocumented. That distinction is useful when assessing what a trial result establishes and where further information would be needed.
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 registry record does not report the original sample-size justification, so the reasons for the planned enrollment cannot be evaluated from this record. Planning illustrations based on observed effects are not a replacement for that rationale and should not be interpreted as observed power. Details of the statistical analysis plan, including prespecified hypotheses and analysis populations beyond the primary endpoint eligibility rule, are also not reported in the registry record.
Missing outcome data are a particular interpretive limitation because the endpoint population required a post-baseline measurement. The record does not report the number of randomized participants who lacked qualifying measurements, the reasons for missingness, or the methods used to handle missing outcomes. It also does not report sensitivity analyses that could show how assumptions about missing data affect the estimates.
The sponsor reports three pairwise tests, but no multiplicity adjustment or testing hierarchy is described. The registry does not report whether other analyses were planned, whether interim analyses took place, or whether the endpoint analysis was adjusted for baseline values. These omissions prevent a complete assessment of the inferential framework. In addition, no standard deviation or participant-level distribution is posted for the primary endpoint, limiting independent evaluation of variability and model assumptions.
The trial concerns Japanese postmenopausal subjects with osteoporosis and reports a 12-month BMD endpoint. The record does not establish how directly these findings apply to other populations, follow-up periods, or outcomes. The posted primary endpoint does not answer questions about fractures or longer-term outcomes. Safety information is presented as descriptive counts and listed event terms; the available record does not provide a full comparative safety analysis or establish causality for individual events.
These limitations do not negate the reported values. They define the scope of interpretation: the means, confidence intervals, and sponsor-reported tests describe the recorded outcome analysis, while several design and analysis details necessary for broader conclusions are not reported in the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Randomized, Double-blind, Placebo-controlled, Dose Response Study of AMG 162 (Denosumab) in Japanese Postmenopausal Osteoporotic Subjects — NCT00306189.
- Registry record last updated 2013-06-20; status last verified 2013-06.
- Results first posted 2010-01-27.
- 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.
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19. Record Summary
NCT00306189 is a completed randomized, double-blind, parallel-group phase 2 study sponsored by Amgen. It enrolled 212 Japanese postmenopausal subjects with osteoporosis and compared placebo with denosumab 14 mg, 60 mg, or 100 mg administered once every 6 months, as described in the study objective.
The primary endpoint was lumbar spine BMD percent change from baseline at month 12, assessed by dual energy X-ray absorptiometry. The registry reports group means and 95% confidence intervals for the endpoint analysis population, along with three two-sided sponsor t-tests comparing each dose group with placebo. All three reported p-values are p < 0.001.
The registry also records serious and other adverse-event counts. The detailed handling of missing outcomes, multiplicity, the original sample-size justification, and several aspects of the statistical plan are not reported in the registry record. The findings therefore describe the posted BMD results and analyses without resolving those additional methodological questions.