Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection (NCT01232127), a non-randomized phase 4 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir.

2. Clinical Question

3. Trial Design

This was a Phase 4, open-label, non-randomized drug-interaction study. The registry classifies its model as single-group, while also listing three regimen descriptions: atazanavir/ritonavir at 300/100 with TDF and at least one NRTI; atazanavir/ritonavir at 400/100 with the same background medicines plus famotidine 20; and the latter regimen with famotidine 40. Participants were required to already be receiving atazanavir, ritonavir, TDF, and at least one NRTI.

The stated purpose was to assess famotidine, given twice daily, alongside atazanavir administered with ritonavir and tenofovir in participants with HIV infection. The registry record does not report enough detail to establish the sequence in which participants received the listed regimens, whether every participant received each regimen, or the timing of any regimen changes. It identifies no random allocation and no masking. Consequently, the regimen groups should not be read as exchangeable randomized groups. The posted description also cautions that the groups are not a like-for-like control comparison.

Enrollment was 25. The study is recorded as completed, with a start date of 2011-02 and primary completion in 2011-06. Bristol-Myers Squibb is listed as sponsor. The primary pharmacokinetic assessment covered Days 10, 11, 17, 18, 24, and 25 (end of study), with assessment at study discharge for participants who discontinued prematurely. The record does not report the rationale for the enrollment target, the planned sequence of assessments, or the statistical plan used to compare regimen measurements.

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.

Period 1: Days 1-10

Reasons for not completing this period:

Period 2: Days 11-17

Period 3: Days 18-24

Analysis population for the primary outcome, as defined in the registry: Participants who received study drug and had adequate PK profiles.

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 Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir, measured over Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely..

The primary endpoint concerns maximum observed plasma concentration (Cmax) and trough observed plasma concentration (Ctrough) for atazanavir and ritonavir, measured in ng/mL. Cmax captures the highest concentration observed in a pharmacokinetic profile. Ctrough represents the measured concentration at the trough point specified by the study. In general, these measures help characterize drug exposure across a dosing interval and can be used in drug-interaction studies to examine whether coadministered medicines are associated with changes in concentration.

The registry describes the endpoint summary as a geometric mean with geometric coefficient of variation as the measure of dispersion. A geometric mean summarizes measurements on a multiplicative scale, which can be useful for concentration data that vary proportionally. The geometric coefficient of variation describes relative variability around that summary; it is not the same as a confidence interval and does not, by itself, express the precision of a treatment comparison.

The stated assessment times were Days 10, 11, 17, 18, 24, and 25 (end of study), and study discharge for participants who discontinued prematurely. The endpoint population was participants who received study drug and had adequate PK profiles. Numerical values for Cmax, Ctrough, the geometric means, or the geometric coefficients of variation are not reported in the registry record. Without those results, neither the observed concentration pattern nor its uncertainty can be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information describes pharmacokinetic summaries and the planned measurement context, but does not report a complete statistical analysis plan or numerical primary endpoint results. The concepts below explain how such measures are generally interpreted; they do not establish which additional analyses were performed in this study.

What does Cmax measure?

Cmax is the maximum observed plasma concentration in a pharmacokinetic profile. It is used to describe the peak concentration reached during the observed sampling period. Its interpretation depends on the dosing and sampling context, because a measured maximum is based on the concentrations collected at the scheduled sampling times. The record identifies Cmax as a primary measure for atazanavir and ritonavir and gives its unit as ng/mL. It does not report the individual concentration observations or numerical Cmax summaries.

What does Ctrough measure?

Ctrough is the observed trough plasma concentration. In general, trough measures characterize concentration at the low point associated with a dosing interval. It is considered alongside a peak measure because the two summarize different parts of the concentration profile. The registry record names Ctrough for both atazanavir and ritonavir but does not give numerical results, a detailed operational definition, or the sampling schedule within each assessment day.

Why use a geometric mean?

The registry specifies a geometric mean. As a general statistical approach, a geometric mean is appropriate for positive measurements when variability is more naturally understood in proportional rather than additive terms. It is calculated on a logarithmic scale and then expressed back on the original scale. This can make concentration summaries less dominated by unusually high measurements than an arithmetic mean, although the suitability of a summary depends on the data distribution and analysis plan. The record does not report the transformation details or the distribution of the observed concentration values.

The geometric coefficient of variation is listed as the dispersion measure. In general, it describes relative spread on a multiplicative scale. It should not be interpreted as a confidence interval around the geometric mean: a measure of variability among observations and a measure of uncertainty in an estimated mean answer different questions. The registry record does not report confidence intervals or other uncertainty intervals for the primary endpoint.

What does the timing tell the reader?

The primary endpoint timeframe lists Days 10, 11, 17, 18, 24, and 25 (end of study), with measurement at study discharge for participants who discontinued prematurely. This identifies the assessment days recorded in the registry, but does not explain whether these were separate regimen periods, how sampling was distributed within a day, or how repeated measurements were summarized. Those design details are not reported in the registry record. The wording also does not establish that every participant contributed an observation at every listed time.

How should the regimen comparisons be viewed?

The record lists atazanavir/ritonavir at 300/100 without famotidine and atazanavir/ritonavir at 400/100 with famotidine 20 or 40. This is a non-randomized study with no masking, and the listed regimens differ in more than famotidine exposure. In general, treatment comparisons are easier to interpret when groups differ only in the intervention of interest and allocation makes other factors comparable. Those conditions cannot be assumed. The registry expressly states that the arms are not a like-for-like control comparison.

The sample-size illustrations associated with the posted results are planning illustrations based on the observed effect, not the study's original design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning row considers a stated fraction of the observed effect. These illustrations are not observed power and should not be mistaken for the study's enrollment justification. The record does not report a sample-size justification for the trial. No numerical illustration results are described in this discussion.

General interpretation of a confidence interval is that it expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval usually indicates greater precision than a wide interval, but the interval cannot correct for systematic limitations such as non-randomized allocation or regimen differences. No primary endpoint confidence intervals are reported in the registry record, so precision cannot be evaluated from those results.

What analysis details are absent?

The registry record does not report the statistical model, any adjustment variables, a method for handling repeated observations, a missing-data procedure, or a formal comparison test for the primary endpoint. It records no analyses. The description of geometric means and geometric coefficients of variation identifies summary statistics, but does not establish how comparisons were estimated or tested. Accordingly, no p-value, effect estimate, or uncertainty statement for the primary pharmacokinetic question can be drawn from the information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary pharmacokinetic endpoint and several secondary safety outcome categories, including deaths, serious adverse events, adverse events leading to discontinuation, adverse events and events of clinical interest, vital signs, electrocardiogram findings, and laboratory test results. It gives no multiplicity strategy, such as a hierarchy of hypotheses or adjustment across outcomes. The approach to repeated measurements across the listed assessment days is also not reported. No claim about control of false-positive findings across endpoints can therefore be made.

Missing-data methods are not reported in the registry record. The primary endpoint population is described as participants who received study drug and had adequate PK profiles, but the record does not define adequacy, state how many profiles were available, or explain how incomplete profiles or missing time points were handled. It does not say whether any measurements were imputed, excluded, or analyzed using another method. The effect of missingness on the estimates cannot be assessed from the recorded information.

The record gives an enrollment of 25, while the primary endpoint population is defined by drug receipt and adequate profiles rather than by enrollment alone. No endpoint-specific analysis counts are reported. The registry records no analyses, and no statistical analysis plan, interim analysis, or sample-size justification is reported. The sample-size illustrations use planning assumptions and are not evidence of observed power or of the study's original design choices.

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 non-serious adverse event terms

The posted safety counts distinguish serious adverse events from other adverse events. For the atazanavir/ritonavir 300/100 regimen with TDF and at least one NRTI, the serious adverse event count is 0 among 25 at risk, and the other-adverse-event count is 4 among 25 at risk. For the 400/100 regimen with famotidine 20, the serious count is 0 among 25 at risk, and the other count is 6 among 25 at risk. For the 400/100 regimen with famotidine 40, the serious count is 0 among 24 at risk, and the other count is 1 among 24 at risk.

These are counts as recorded, not comparative risk estimates. The groups were non-randomized and are not described as like-for-like controls, so the counts should not be interpreted as evidence that a regimen caused more or fewer events. The record does not provide the event terms underlying the other-adverse-event counts in this information. Death counts are not reported in the registry record. A zero serious-event count in the listed groups does not establish that serious events are impossible or that the regimens have equivalent safety.

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

This study addresses a focused pharmacokinetic question: whether famotidine, given twice daily, affects measured atazanavir and ritonavir concentrations in participants with HIV infection who were already receiving atazanavir, ritonavir, TDF, and at least one NRTI. The primary endpoint names peak and trough concentrations and specifies geometric means and geometric coefficients of variation. Those details establish what the study intended to measure.

The registry record does not report numerical primary endpoint results. It therefore cannot establish the concentration levels observed, the size or direction of any change, or the precision of an estimate. Lack of numerical results in the record is not evidence of no effect. A conclusion about the pharmacokinetic findings would require the actual outcome values and an analysis that can be evaluated.

The design also does not support a simple causal interpretation of differences between the listed regimens. Allocation was non-randomized, the study was open-label, and the regimen descriptions vary in both famotidine exposure and atazanavir/ritonavir dose. The registry warns that the arms are not a like-for-like comparison. These features prevent a clean attribution of any between-regimen difference to famotidine alone based on this entry.

The safety summaries record zero serious adverse events in each displayed regimen and other-adverse-event counts of 4, 6, and 1. These counts do not show whether the groups differ in underlying risk, and the record does not provide the terms for the other events or death counts. They should be read as descriptive registry counts, not as definitive comparative safety evidence.

In general, pharmacokinetic studies can help characterize exposure and inform further evaluation of drug interactions. This record identifies that scientific aim but, without reported primary endpoint estimates and fuller analysis details, does not allow a reader to quantify the observed interaction or its uncertainty.

13. Why This Trial Matters Statistically

Drug-interaction questions often concern whether one medicine is associated with changes in another medicine's concentration. This study is statistically relevant because it identifies measurable pharmacokinetic endpoints—Cmax and Ctrough for atazanavir and ritonavir—and records an assessment schedule and a defined endpoint population. These features make clear that the central question concerns drug exposure rather than a clinical outcome such as symptom change.

The record also illustrates why comparison structure matters. A non-randomized study may be useful for describing measurements under specified regimens, but differences between groups can reflect more than the medicine of interest. Here, the listed atazanavir/ritonavir doses differ between the regimen without famotidine and those with famotidine, and the registry warns that the groups are not like-for-like controls. Statistical interpretation must therefore stay close to the actual design rather than treating the regimen labels as randomized alternatives.

Another important issue is the distinction between a summary and its precision. Geometric means describe concentration levels on a multiplicative scale, while geometric coefficients of variation describe relative variability. Neither alone supplies a complete account of uncertainty in a comparison. The registry record does not report numerical endpoint estimates or confidence intervals, so the size and precision of the pharmacokinetic findings remain unavailable from this entry.

Finally, safety counts and planning illustrations answer different questions from observed pharmacokinetic results. Descriptive adverse-event counts do not establish comparative safety, and sample-size illustrations based on an observed effect are not observed power or a record of the trial's original design. Keeping these distinctions clear prevents the available registry information from being interpreted more strongly than it supports.

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 primary limitation for interpretation is that numerical Cmax and Ctrough results are not reported in the registry record. The stated geometric means and geometric coefficients of variation are summary methods, not results. Without endpoint estimates, uncertainty intervals, and analysis details, the magnitude and precision of the pharmacokinetic findings cannot be assessed.

The comparison is non-randomized and open-label. The registry explicitly says the arms are not a like-for-like control comparison. In addition, the regimen without famotidine lists atazanavir/ritonavir at 300/100, while the famotidine regimens list 400/100. Any difference across these regimen descriptions would not isolate famotidine's contribution on the information recorded.

The registry classifies the model as single-group but also lists three regimen descriptions. It does not explain how participants moved between regimens, whether all participants received each regimen, or how measurements from different periods were analyzed. The timing information lists assessment days, but does not specify detailed within-day sampling or the handling of repeated profiles. These missing details constrain evaluation of the design and analysis.

The primary analysis population requires receipt of study drug and adequate PK profiles, but the record does not report endpoint-specific participant counts, a definition of adequate profiles, or missing-data handling. It also does not report a statistical analysis plan, multiplicity approach, sample-size justification, or numerical primary results. Safety counts are descriptive, with death counts and event terms for the other-adverse-event category not reported in the registry record. These limitations are specific to what this registry entry records and do not establish that the omitted information was not collected elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection — NCT01232127.
• Registry record last updated 2012-08-31; status last verified 2012-08.
• Results first posted 2012-08-28.
• 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 4, open-label, non-randomized drug-interaction study sponsored by Bristol-Myers Squibb. It enrolled 25 participants with HIV infection and assessed famotidine alongside atazanavir, ritonavir, TDF, and at least one NRTI. The primary endpoint was maximum observed and trough plasma concentrations of atazanavir and ritonavir, summarized using geometric means and geometric coefficients of variation at the listed assessment times.

Three regimen descriptions are recorded, but the registry cautions that these are not like-for-like controls. Numerical primary endpoint results and analyses are not reported in the registry record. Safety summaries list zero serious adverse events in each displayed regimen and other-adverse-event counts of 4, 6, and 1; death counts are not reported in the registry record. The record identifies the study question and outcome definitions but does not permit assessment of the size or precision of the primary pharmacokinetic findings.