Safety Study of HZT-501 in Patients Who Require Long-Term Daily Non-steroidal Anti-inflammatory Drug Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of HZT-501 in Patients Who Require Long-Term Daily Non-steroidal Anti-inflammatory Drug Treatment (NCT00984815), a non-randomized phase 3 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events.

2. Clinical Question

This question is descriptive: it concerns events recorded during exposure to HZT-501 in the study population. Because there is no comparator arm, the study cannot distinguish events associated with treatment from events that might have occurred without it. Nor can it establish how the observed safety experience compares with another treatment. Such limits do not make the counts uninformative; they define what those counts can support. The registry record does not report a causal comparison or an estimate of treatment effect.

3. Trial Design

This was a Phase 3, open-label safety study of HZT-501. The registry records non-randomized allocation, no masking, and a single-group model. There was no control arm. The study was sponsored by Amgen, began in 2009-09, reached primary completion in 2011-07, and is recorded as completed. Enrollment was 86.

HZT-501 was described as a fixed-dose combination oral tablet containing 800 mg ibuprofen and 26.6 mg famotidine. The stated purpose was to evaluate long-term safety for people requiring long-term NSAID treatment. The single arm received open-label HZT-501. The registry record does not report a treatment schedule or further details of exposure beyond the safety population definition and the outcome timeframe.

The primary outcome was the number of participants with treatment-emergent adverse events over 54 weeks. The primary population is described as participants enrolled who received at least one dose of study drug. The record also lists three secondary outcomes, each assessing change from baseline at 54 weeks using a scale of the Severity of Dyspepsia Assessment questionnaire: pain intensity, non-pain symptoms, and satisfaction with dyspepsia-related health.

A single-group safety study can describe events observed among participants during treatment. It cannot estimate a between-group treatment effect, because no like-for-like control group was included. Open-label conduct means the study is recorded as unmasked; the registry record does not report additional procedures for limiting knowledge of treatment. Further details of eligibility criteria, follow-up procedures, dose modifications, and the protocol 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.

Before assignment: Eligible participants, 40-80 years of age inclusive, expected to require daily administration of a non-steroidal anti-inflammatory drug (NSAID) for at least the coming 12 months were enrolled. Of the approximately 100 participants enrolled, it was expected that at least 30 would complete the 54-week treatment period.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants enrolled and who received at least one dose of study drug comprised the 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events, measured over 54 weeks.

The primary endpoint is the number of participants with treatment-emergent adverse events during the 54-week timeframe. It is a count of participants, rather than a measure of event severity or a comparison of event rates between groups. The registry defines the safety population as all participants enrolled who received at least one dose of study drug. The posted results give 86 participants at risk and report 76 participants affected for the other adverse event count; serious adverse events are reported separately, with 9 participants affected. These categories should not be combined into a total, because the record does not state whether participants could appear in both.

In general, a participant-based safety endpoint is useful for describing how many people experienced at least one event during the defined observation period. It does not, by itself, show how many events each person had, how long participants were exposed, or the timing and duration of events. Nor does an uncontrolled count establish that treatment caused an event. The endpoint is relevant to a safety-focused study because it records adverse experiences during treatment, but interpretation depends on the population definition, observation period, event classification, and completeness of reporting.

The registry record does not report additional endpoint detail about how treatment-emergent events were defined or how they were attributed. It also does not report a comparative endpoint estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant count. For the HZT-501 group, the posted results report the number at risk and the number affected for serious and other adverse events. A count is straightforward to interpret as a number of participants, but it does not capture every feature of safety experience. It does not indicate how many events a participant had, how long an event lasted, when it occurred, or whether multiple event terms applied to the same participant.

In general, a proportion is often used to place an event count in the context of the number of participants at risk. However, no new proportions are calculated in this interpretation. The record displays 1.2% for each of the listed serious adverse event terms. Those percentages should be read as the registry's reported values, not as a basis for inferring unreported event counts or participant overlap. The record does not explain the calculation details for those term-level percentages.

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model. A narrower interval indicates greater precision under that model, while a wider interval indicates less precision. The registry record does not report confidence intervals for these event counts. Without an interval, the precision of the reported counts cannot be expressed as a range of plausible values using the registry results alone. The absence of a confidence interval also does not transform a descriptive count into evidence for or against a treatment effect.

There is no randomized comparator, so there is no between-group contrast to estimate. In general, randomization helps balance measured and unmeasured characteristics across groups, supporting a more credible treatment comparison. A single-group study instead describes events observed among those treated. Participants may have underlying conditions and other influences on their health, and the registry record does not provide a counterfactual group to separate these influences from treatment exposure. Accordingly, causal attribution cannot be made from the design alone.

The record identifies the primary endpoint timeframe as 54 weeks. In general, the length and completeness of follow-up affect interpretation of safety findings: events can only be observed while participants are under observation, and unequal exposure time can complicate comparisons. Here, no comparison is available, and the record does not report individual follow-up durations, person-time, or how missing observations were handled. The reported at-risk count is a participant count, not a measure of exposure time.

The registry describes the safety population as all participants enrolled who received at least one dose of study drug. This definition sets the population for the primary safety outcome. The record does not report how many enrolled participants did not receive a dose, whether any participants were excluded from particular outcome summaries, or whether all participants completed follow-up. Those details are not reported in the registry record.

The registry lists an enrollment of 86, while the safety group results list 86 participants at risk. These values are reported as written; no additional total or derived count is needed to interpret the design. The record's primary outcome count is not an event rate per unit of time, and it should not be read as an estimate of the number of events in a broader population.

Planning illustrations use an assumed two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects set as fractions of an observed effect. Such calculations are planning illustrations, not observed power and not a description of this single-group trial's design. In general, sample-size planning asks what sample size might be needed for a specified statistical objective under stated assumptions. It does not establish that a study had that power after completion, and it does not replace the observed results. The registry record does not report the trial's own sample-size justification or design assumptions.

General explanation of over-dispersion: for count data, over-dispersion occurs when variability is greater than a model assumes. If present, uncertainty estimates from a model that assumes less variability can be too small. This study's primary outcome is a participant count, and the registry record does not report a count-model analysis or an assessment of over-dispersion. This concept therefore does not supply an additional result for this study.

The registry reports no analyses. It does not report adjusted estimates, inferential tests, model specifications, or uncertainty intervals for the primary outcome. The appropriate statistical reading is consequently descriptive: retain the reported group counts and serious event terms, and avoid treating them as evidence from a controlled comparison.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("HZT-501")
n      <- c(86)
events <- c(76)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  HZT-501  86  76  88.4  79.7  94.3  79.9  93.6  79.9  93.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary adverse event outcome and three secondary dyspepsia questionnaire outcomes. The secondary measures concern change from baseline at 54 weeks in pain intensity, non-pain symptoms, and satisfaction with dyspepsia-related health. The record does not report results for those secondary measures in the information available for this analysis.

In general, testing multiple outcomes can increase the chance of at least one apparently notable result arising by chance. Statistical plans may address this through a prespecified hierarchy or an adjustment for multiple testing. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes, if any, were included in formal inferential testing. It also records no analyses. No multiplicity-adjusted interpretation can therefore be drawn from the registry record.

The record defines the safety population as participants enrolled who received at least one dose. It does not report a missing-data method, the number of participants with incomplete outcome information, reasons for missingness, or how missing observations were handled. Completion status does not, by itself, establish that every participant contributed complete data at every assessment. The available record does not allow an assessment of whether missingness could have affected the reported counts or secondary outcomes.

The registry record also does not report an analysis plan, interim analyses, or a sample-size justification. These details should not be inferred from the posted results or from planning illustrations. The reported safety counts can be read descriptively, but uncertainty due to missing observations and the handling of multiple outcomes cannot be evaluated from the information recorded.

12. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (1.2%), gastric ulcer (1.2%), small intestinal obstruction (1.2%), cellulitis staphylococcal (1.2%), escherichia sepsis (1.2%).

The HZT-501 group has 86 participants at risk in the posted results. The record reports 9 participants affected by serious adverse events and 76 affected by other adverse events. These are separate reported counts; the record does not state whether the same participants appear in both categories. They should not be added together to make a total number of affected participants.

The listed serious adverse event terms are angina unstable, gastric ulcer, small intestinal obstruction, cellulitis staphylococcal, escherichia sepsis, and pyelonephritis. Each term is accompanied by 1.2%. The registry record does not report whether a participant could have more than one serious event, whether the terms overlap, or the event counts behind each percentage. The term list should therefore be read as a record of reported serious event types, not as a set of mutually exclusive participant groups.

Deaths are not reported in the registry record. That wording indicates an absence of a reported death count in this record, not proof that no deaths occurred. In general, safety counts describe events recorded during a study; they do not establish causation. The single-group design also offers no control group for comparison.

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

The results establish that the registry records adverse events among participants treated with HZT-501 in an open-label, single-group study. The primary outcome is framed as the number of participants with treatment-emergent adverse events over 54 weeks. The posted results report the serious and other adverse event counts, along with serious event terms and their displayed percentages. These are descriptive findings for the study group.

They do not establish that HZT-501 caused any particular event. A treatment-emergent event is an event recorded after treatment begins under the endpoint definition; that label alone does not show causation. The study has no randomized comparator, so it cannot show whether the reported experience differs from that under another treatment or from what would have happened without HZT-501.

The findings also do not establish the relative safety of HZT-501 compared with other medicines, nor do they describe risk for every person who might use the treatment. The registry record does not report a comparative effect estimate, confidence interval, or detailed follow-up accounting. It does not report the results of the listed secondary dyspepsia outcomes in the information available for this analysis. These omissions limit what can be concluded about precision, comparative effects, and symptom changes.

In general, an uncontrolled safety study can provide a structured account of events observed during treatment and can identify event types recorded in the study. It is one kind of evidence, but its descriptive counts should not be interpreted as a causal treatment effect. The record's limitations are especially important when considering whether the event experience is higher or lower than it would be in a comparable untreated or differently treated population: no such comparison is reported.

Thus, the central statistical conclusion is narrow. The registry describes adverse events in the enrolled HZT-501 group during the stated timeframe, but does not provide the comparative or inferential evidence needed to quantify a treatment-related difference. No medical recommendation follows from these study counts alone.

14. Why This Trial Matters Statistically

This trial matters statistically because safety outcomes in a single-group study are easy to overinterpret. A count of participants with events is direct and clinically legible, but it remains a description of what was recorded among treated participants. Without a comparator, the count cannot answer whether the event experience was greater or smaller than it would have been under another treatment or without treatment.

The design also clarifies why the endpoint and population definitions matter. The primary outcome concerns participants with treatment-emergent adverse events over 54 weeks, and the safety population includes enrolled participants who received at least one dose. These choices define what the reported counts represent. They do not, however, establish the amount of observation time for each participant or show whether all participants completed follow-up.

The record lists serious adverse event terms and percentages as well as counts of affected participants. These are different kinds of safety information. A participant count describes how many people were affected within a category; a term list describes event types. Without information about overlap, event counts, and timing, the terms cannot be treated as mutually exclusive outcomes or added into a single total.

The study also illustrates the distinction between study design and planning calculations. Planning illustrations based on assumed two-arm comparisons do not turn a single-group study into a comparative trial, and they are not observed power. The registry record does not report the trial's own sample-size justification or statistical analysis plan. Recognizing these boundaries helps readers keep descriptive safety evidence separate from comparative or causal evidence.

For clinical researchers and biostatisticians, the lesson is methodological: match the strength of the conclusion to the design, endpoint, and reporting. Here, the record supports a descriptive account, while leaving comparative effect, precision, and some details of missing data and analysis unreported.

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 principal limitation is the single-group, non-randomized design. Without a control arm, there is no like-for-like comparison to estimate how the adverse event experience differs from another treatment or from no study treatment. Open-label conduct and the absence of masking are also recorded; the registry does not describe any additional safeguards for outcome assessment.

The primary outcome is a participant count, and the registry record does not provide event timing, event duration, event-level counts, or individual exposure time. The record lists serious and other affected-participant counts but does not state whether the categories overlap. The serious adverse event terms and their percentages are reported without enough detail to establish whether terms represent separate participants or repeated events.

The registry defines the safety population as enrolled participants who received at least one dose, but does not report a detailed account of participant follow-up, missing outcomes, or reasons for incomplete data. It does not report how missing information was handled. No confidence intervals, inferential tests, adjusted estimates, or analysis details are recorded.

Although secondary dyspepsia measures are listed, their results are not reported in the record information. Multiplicity handling, interim analyses, a sample-size justification, and the trial's statistical plan are also not reported in the registry record. Deaths are not reported in the registry record; this should not be taken as confirmation that none occurred.

These limits mean the findings are descriptive and bounded by the study population and recorded follow-up. They do not support a causal or comparative conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety Study of HZT-501 in Patients Who Require Long-Term Daily Non-steroidal Anti-inflammatory Drug Treatment — NCT00984815.
• Registry record last updated 2024-12-18; status last verified 2024-11.
• Results first posted 2013-07-25.
• 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

NCT00984815 is a completed Phase 3, open-label safety study of HZT-501 in people requiring long-term daily NSAID treatment. It is recorded as non-randomized and single-group, with no masking. Enrollment was 86. The study began in 2009-09 and reached primary completion in 2011-07; Amgen is the listed sponsor.

HZT-501 was described as an oral fixed-dose combination of 800 mg ibuprofen and 26.6 mg famotidine. The primary outcome was the number of participants with treatment-emergent adverse events over 54 weeks. The safety population comprised enrolled participants who received at least one dose. The posted results report serious and other adverse event counts and list serious event terms. Three secondary outcomes concern dyspepsia questionnaire changes at 54 weeks.

The record does not report a comparator, inferential analyses, confidence intervals, missing-data methods, or a multiplicity plan. The results therefore support descriptive interpretation of the single study group, not a comparative treatment conclusion.