A Study to Evaluate the Effect of Famotidine and Omeprazole on MK0518 (Raltegravir) Pharmacokinetics in Human Immunodeficiency Virus (HIV)-Infected Patients (0518-054): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effect of Famotidine and Omeprazole on MK0518 (Raltegravir) Pharmacokinetics in Human Immunodeficiency Virus (HIV)-Infected Patients (0518-054) (NCT01000818), a non-randomized phase 1 study. The primary outcome is Plasma Area Under Curve (AUC 0-12 hr ) for Raltegravir.

2. Clinical Question

The clinical-pharmacology question is whether raltegravir exposure, as represented by the measured concentration over the postdose interval, differed across the listed treatment periods. The registry identifies famotidine and omeprazole as the drugs considered alongside raltegravir and identifies raltegravir pharmacokinetics as the subject of the study. It does not report a numerical estimate for any period or a direct statistical contrast between periods.

The sequence is important to interpretation. The record describes an open-label, three-period, fixed-sequence design. It does not describe random assignment to treatment order or a separate concurrent control group. Accordingly, the question is about measurements across the described sequence, not a randomized treatment effect. Any interpretation would need to distinguish the observed period-specific measurements from effects attributable specifically to adding either other drug.

3. Trial Design

The registry classifies this as a Phase 1, open-label, non-randomized, single-group study. It describes a fixed sequence of three periods: MK0518 alone, famotidine with MK0518, and omeprazole with MK0518. The record identifies eighteen HIV-infected patients on a stable MK0518-containing regimen as the study population. It does not state how many participants contributed usable endpoint data in each period.

In a fixed-sequence study, treatments are given in an ordered series rather than assigned randomly to different groups. Here the period descriptions specify the sequence of the three conditions. A within-participant design can make measurements from the same person useful for comparing conditions, because each person can serve as a reference for their own measurements. However, the registry record does not describe the statistical analysis or confirm which measurements were paired in an analysis. The sequence alone does not establish that a contrast isolates the effect of either added drug.

Because assignment was not randomized and masking was absent, the design differs from a blinded randomized comparison. Period, order, time-related changes, or other features of the sequence can be difficult to separate from treatment condition. These are general considerations for fixed-sequence designs; the registry does not report whether they were assessed or how they were handled.

The study status is completed. The record lists one primary outcome measure and two analyses, but does not provide the analysis methods or the numerical endpoint findings. Details such as washout procedures, sampling schedule beyond the stated postdose timeframe, protocol deviations, and the handling of incomplete observations are not reported in the registry record. The record also does not report a statistical analysis plan or sample-size justification. These omissions limit what can be inferred about implementation and analysis, even though the study question and period conditions are identifiable.

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 18 participants were enrolled in the study.

Raltegravir

Famotidine + Raltegravir

Omeprazole + Raltegravir

Analysis population for the primary outcome, as defined in the registry: Eighteen HIV-Infected Patients

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 Plasma Area Under Curve (AUC 0-12 hr ) for Raltegravir, measured over 12 hours postdose.

The primary endpoint is plasma area under the concentration-time curve for raltegravir from zero to twelve hours, with the measurement timeframe described as twelve hours postdose. Area under the curve represents the accumulated plasma concentration over a specified interval. In general, it is used in pharmacokinetic studies as a measure of drug exposure across that interval rather than as a single concentration at one moment.

The registry specifies a geometric mean and a 95% confidence interval as the summary format, with the endpoint expressed in µM*hr. A geometric mean is commonly used for positive measurements that are skewed, because it summarizes values on a multiplicative rather than additive scale. The confidence interval communicates uncertainty about the estimated geometric mean: in general, a narrower interval indicates greater precision, while a wider interval indicates less precision. It does not describe the range containing most individual participant values.

The record’s endpoint description also mentions area under the plasma concentration-time curve and peak concentration, while the primary outcome title specifies the area under the curve. It does not report the numerical estimate, interval limits, or a comparison estimate for any period. The statistical interpretation therefore cannot quantify the observed exposure or the precision of a difference between conditions. Nor does an endpoint summary alone establish why values differed; the design and analysis must also be considered.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a geometric-mean endpoint and a 95% confidence interval, but it does not provide the statistical methods used to estimate them. The concepts below are general explanations of the reported summary types and design, not claims about analyses performed in this study.

What does area under the curve measure?

In general, a concentration-time curve traces how a measured drug concentration changes after dosing. The area under that curve over a defined interval summarizes the accumulated concentration during that interval. The primary endpoint specifies an interval from zero to twelve hours and a timeframe of twelve hours postdose. It is therefore an interval-based pharmacokinetic measure, not a single-timepoint concentration. The registry does not give the sampling schedule or describe how concentrations were combined to obtain each participant’s area.

The endpoint unit is µM*hr. Units matter because they indicate the measurement being summarized: a concentration accumulated over time. The endpoint title names raltegravir, while the study conditions distinguish MK0518 alone from the combinations with famotidine and omeprazole. The record does not give the period-specific values or the exact contrasts used in the two analyses.

Why report a geometric mean?

In general, pharmacokinetic measurements are positive and may have a right-skewed distribution, where a smaller number of high values can pull an arithmetic mean upward. A geometric mean summarizes values using their logarithms and then returns the summary to the original scale. This approach is often useful when variation is more naturally described proportionally than as a fixed additive amount. The registry identifies the geometric mean as the endpoint parameter, but does not state whether values were transformed for analysis or give further distributional details.

A geometric mean is not the same as an arithmetic average. It should be interpreted on its stated scale and in light of the analysis used to calculate it. Without the reported estimate and method details, no numerical interpretation of the geometric mean is possible.

What does a confidence interval communicate?

In general, a confidence interval conveys uncertainty about an estimated quantity under a statistical procedure. Its width reflects precision: narrower intervals indicate more precise estimates than wider intervals, all else being equal. A 95% confidence interval does not describe the spread of all individual measurements, and it is not a range in which 95% of participants’ values necessarily fall. The registry specifies a 95% confidence interval but does not report its limits, so precision cannot be assessed for this endpoint.

How does the sequence affect comparison?

In general, a single-group fixed-sequence design differs from a parallel randomized trial. Each condition is tied to an ordered period, rather than being assigned at random to distinct groups. Repeated measurements within a participant can help control for stable differences between people when an appropriate paired analysis is used. But period and treatment condition may also be entangled: changes over time, order, or carryover can influence measurements. These are general design considerations, not reported findings about this study.

The registry describes the conditions and calls the study fixed-sequence, but it does not report whether there was a washout, the interval between periods, how carryover was assessed, or whether the analyses used paired methods. It is therefore not possible to attribute any unreported difference solely to famotidine or omeprazole.

What can be said about the analysis plan?

The record lists one primary outcome measure and two analyses, but does not describe the model, test, contrast, or adjustment used. It does not report assumptions checks, a statistical analysis plan, or an interim analysis. The absence of those details means that the inferential approach cannot be reconstructed from the registry record. General features of a suitable analysis cannot be substituted for documentation of what the investigators actually did.

The record includes planning illustrations based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such sample-size calculations are planning exercises, not observed power. The record does not include the resulting sample-size values in the registry record for interpretation. Also, the study itself is described as non-randomized and single-group; the assumptions for a hypothetical two-arm illustration should not be mistaken for its actual design.

For time-to-event outcomes, event-based sample-size methods are often used; for other outcomes, planning estimates may be expressed as participants per arm. In general, planning estimates depend on assumed effect size, variability, allocation, and significance criteria. They do not demonstrate that a completed study had adequate precision, and they cannot replace the observed endpoint estimate and its confidence interval. The registry record does not report the original design’s sample-size rationale.

10. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary outcome measure and two analyses. It does not name the analyses, specify which comparisons they represent, or report whether one analysis was designated primary for inference. With several possible comparisons or analyses, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently unusual result under a set of null hypotheses. In general, prespecified methods such as an adjustment or a clear testing hierarchy can address that issue. The registry record does not report whether any such approach was used.

The primary population is described as eighteen HIV-infected patients. The record does not define an analysis population, such as an intention-to-treat, per-protocol, or pharmacokinetic-evaluable set. It also does not say how many participants contributed observations to each period-specific analysis. The described population should not automatically be treated as the number with complete data for every endpoint analysis.

Missing-data handling is not reported in the registry record. There is no description of incomplete concentration measurements, missed visits, exclusions, imputation, or sensitivity analyses. In general, missingness can affect an estimate when the observed measurements do not adequately represent those that are missing. Without documentation about the amount, pattern, and handling of missing data, that potential effect cannot be assessed.

The record also does not report protocol deviations or analysis exclusions. These omissions matter because decisions about which observations enter an analysis can affect both the estimate and its uncertainty. No conclusion about multiplicity control, missing-data bias, or the final analysis population can be drawn from the registry information.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ruptured coronary artery plaque (5.6%).

The safety entries are organized by named groups: Prestudy, 400 mg Raltegravir, 20 mg Famotidine + 400 mg Raltegravir, and 20 mg Omeprazole + 400 mg Raltegravir. For each group, the record lists eighteen as at risk. The serious-event affected count is one for Prestudy and zero for each of the three treatment groups. The other-event affected counts are zero for Prestudy, two for 400 mg Raltegravir, one for famotidine with raltegravir, and six for omeprazole with raltegravir.

These are group-level counts as recorded, not rates calculated for comparison. They should not be added across groups: the design is a fixed sequence in a single group, and the entries do not establish that each period represents a distinct set of participants. The record does not report whether events were judged related to treatment, their timing or duration, or how event categories were defined. Death counts are not reported in the registry record.

The record lists “Ruptured coronary artery plaque” among the top serious terms at 5.6%. It does not state the denominator or provide further context for that percentage in the registry record. The listed term and percentage do not establish causality, and the adverse-event counts should be interpreted descriptively rather than as comparative treatment effects.

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

This study record is useful for identifying a focused pharmacokinetic question: raltegravir exposure was assessed across a sequence involving MK0518 alone, famotidine with MK0518, and omeprazole with MK0518. The primary endpoint was area under the plasma concentration-time curve from zero to twelve hours, summarized as a geometric mean with a 95% confidence interval. Those details clarify what the study intended to measure.

The record does not report the endpoint estimates or the confidence interval limits. Therefore, it does not establish the direction or magnitude of any difference in exposure, or how precisely such a difference was estimated. It also does not report a numerical comparison between periods. Without these results, no claim about an increase, decrease, or absence of change can be made from the registry information.

The design does not support treating the three conditions as randomized, independent arms. It is an open-label, non-randomized, single-group study with a fixed sequence. In general, period and order may be relevant when interpreting sequential measurements. The registry does not report enough analytic detail to determine how those considerations were handled, so a causal effect attributable to either famotidine or omeprazole cannot be established from the record alone.

The safety entries provide affected counts by listed group and a serious-event term. They are descriptive entries, not proof that a drug caused an event. The registry does not provide the context needed to assess event attribution or compare safety between conditions.

The appropriate conclusion is limited: the registry documents the design, endpoint definition, and certain safety counts, but does not provide the numerical pharmacokinetic findings needed to answer the study’s central question. This is a limitation of the registry record as reported, not evidence for a particular pharmacokinetic result.

13. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the distinction between a clear pharmacokinetic question and the evidence needed to answer it. The record specifies raltegravir area under the concentration-time curve over a defined postdose interval and identifies a geometric mean with a 95% confidence interval as the summary. These choices make the intended measurement interpretable in general terms.

At the same time, the design is a non-randomized fixed sequence in a single group. Such a structure differs from a randomized parallel comparison. Repeated observations can be informative, but the order of conditions and the passage of time can complicate attribution. A careful interpretation depends on the analysis, measurement schedule, and handling of potential period effects. Those details are not reported in the registry record.

The record also demonstrates why endpoint definitions alone are not enough. Without numerical estimates, interval limits, and a description of the contrasts, readers cannot judge effect size, precision, or the evidence supporting a statistical comparison. Listing two analyses without identifying them leaves uncertainty about how the findings were organized and whether multiplicity was addressed.

Finally, the safety counts require attention to study structure. Counts listed under sequential conditions should not be casually treated as though they arose from separate randomized groups. The available entries are descriptive and do not document causal attribution. Together, these features make the study a useful example of how design and reporting determine the strength of conclusions that can be drawn from a clinical pharmacology record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most immediate limitation is that the registry record does not report numerical results for the primary pharmacokinetic endpoint. Although it identifies the geometric-mean summary and 95% confidence interval, it gives neither an estimate nor interval limits. The direction, magnitude, and precision of any period difference are therefore unavailable.

The design is described as non-randomized, open-label, single-group, and fixed-sequence. The period descriptions identify MK0518 alone followed by combinations with famotidine and omeprazole, but the record does not report whether order effects, period effects, or carryover were assessed. It does not describe washout procedures or the timing between periods. These gaps prevent evaluation of how well an observed difference, if one were reported, could be attributed to the added drug.

Additional details are absent: the registry record does not describe the concentration-sampling schedule, analysis model, exact contrasts, missing-data approach, analysis population, or treatment of protocol deviations. It lists two analyses but does not identify them. The original sample-size rationale and statistical analysis plan are also not reported.

The safety entries lack treatment-relatedness assessments and further context for the serious-event term. The record does not report death counts. The information therefore supports only a limited descriptive reading of safety, not a causal comparison. These limitations concern what the registry record reports; they do not establish that the unreported procedures or analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effect of Famotidine and Omeprazole on MK0518 (Raltegravir) Pharmacokinetics in Human Immunodeficiency Virus (HIV)-Infected Patients (0518-054) — NCT01000818.
• Registry record last updated 2017-03-21; status last verified 2017-02.
• Results first posted 2010-05-28.
• 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.

18. Record Summary

The registry record describes a completed Phase 1, open-label, non-randomized, single-group, fixed-sequence study in HIV-infected patients receiving MK0518, or raltegravir, as part of a stable regimen. The three described periods are MK0518 alone, famotidine with MK0518, and omeprazole with MK0518.

The primary endpoint is raltegravir plasma area under the curve from zero to twelve hours, expressed in µM*hr and summarized as a geometric mean with a 95% confidence interval. The record lists one outcome measure and two analyses, but does not report numerical endpoint results or explain the analyses.

Safety counts are listed by prestudy and treatment groups. The record does not report event attribution or death counts. Important details about the analysis population, missing data, statistical methods, and sample-size rationale are not reported in the registry record. Consequently, the record establishes the study question and design but does not permit a numerical interpretation of the primary pharmacokinetic findings.