A Study To Evaluate An Interaction Between Maraviroc And Raltegravir In Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Evaluate An Interaction Between Maraviroc And Raltegravir In Healthy Subjects (NCT00666705), a non-randomized phase 4 study. The primary outcome is Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ).

2. Clinical Question

This is a pharmacokinetic interaction question, not a clinical-outcome comparison. It concerns drug concentration over a dosing interval in healthy subjects. The registry identifies pharmacokinetic assessments on Day 11 for maraviroc and on Day 14 for maraviroc and raltegravir. It does not report the concentration measurements, the group or period means, a contrast between conditions, or an estimate of uncertainty. Consequently, the direction and size of any observed difference cannot be described from the registry record.

3. Trial Design

This was an open-label Phase 4 study with a single-group model and non-randomized allocation. The registry lists 18 enrolled healthy subjects and marks the study as completed. The start is recorded as 2008-02 and primary completion as 2008-03. ViiV Healthcare is listed as the sponsor.

The registry identifies three treatment conditions: maraviroc alone, maraviroc with raltegravir, and raltegravir alone. The primary pharmacokinetic comparison is between maraviroc with raltegravir and maraviroc alone. Although the record lists these conditions, it does not provide descriptive schedules for the arms. The dosing details, treatment sequence, duration of exposure in each condition, and any washout arrangements are not reported in the registry record. It is therefore not possible to characterize the study more specifically as a particular sequence design from this information.

Neither randomization nor masking was used: allocation is listed as non-randomized and masking as none. These features matter when interpreting treatment comparisons. A non-randomized, single-group study is not a parallel randomized comparison in which separate groups are allocated to treatment and control. The registry itself cautions that its arms are not a like-for-like control comparison. Any interpretation should remain tied to the stated pharmacokinetic conditions and should not imply that the design controls all sources of variation in the way a randomized comparison might.

The stated pharmacokinetic analysis population consists of subjects enrolled and treated who have at least one primary-interest pharmacokinetic parameter in at least one treatment period. The number included in that population, and the number contributing to each condition or endpoint, are not reported in the registry record. The listed enrollment should not be taken as proof that every enrolled subject contributed a complete result for every treatment condition.

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: Subjects were to be healthy male or female subjects between the ages of 18 and 55 years, inclusive. Subjects were required to meet all eligibility criteria prior to randomization into the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic (PK) parameter analysis population is defined as all subjects enrolled and treated who have at least one of the PK parameters of primary interest in at least one treatment period.

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 Maraviroc Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-time Profile Over the Dosing Interval (AUCτ), measured over Days 11 and 14.

The primary endpoint is maraviroc AUCτ, the area under the plasma concentration-time profile over the dosing interval. In general, an area-under-the-curve measure captures drug exposure across a period rather than describing a concentration at a single sampling time. It is used in pharmacokinetic research to compare exposure under different treatment conditions.

The registry frames the primary question as the effect of raltegravir on maraviroc pharmacokinetics. The test condition is maraviroc co-administered with raltegravir; the reference condition is maraviroc administered alone. The specified unit is ng.hr/mL, and the summary parameter is the mean with standard deviation. Pharmacokinetics were assessed on Day 11 for maraviroc and on Day 14 for maraviroc and raltegravir.

The endpoint’s purpose is to describe exposure, not to measure a clinical benefit or harm. A difference in AUCτ, if observed, would be a pharmacokinetic finding; its clinical implications would require evidence and context beyond the endpoint itself. The numerical means, standard deviations, comparison estimate, and uncertainty around the primary comparison are not reported in the registry record. Thus, the endpoint definition is available, but the magnitude and precision of the result cannot be assessed from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous pharmacokinetic endpoint, summarized as a mean with standard deviation. These are descriptive statistics: the mean gives a central summary of measured exposure, while the standard deviation describes how observations vary around that mean. Neither statistic, by itself, quantifies uncertainty in a comparison between treatment conditions. The numerical summaries for the primary endpoint are not reported in the registry record.

What does AUCτ represent?

In general, AUCτ is the area under a concentration-time curve during a dosing interval. It integrates concentration information across time, so it represents exposure over that interval rather than a single concentration reading. The registry gives the unit as ng.hr/mL and specifies maraviroc AUCτ as the primary pharmacokinetic parameter. It describes assessment on Day 11 for maraviroc and on Day 14 for maraviroc and raltegravir. The sampling schedule and the method used to derive the area are not reported in the registry record.

How should the comparison be understood?

The stated primary contrast compares maraviroc co-administered with raltegravir, labelled the test condition, against maraviroc administered alone, labelled the reference condition. This is the comparison relevant to the stated question about raltegravir’s effect on maraviroc pharmacokinetics. Raltegravir alone is also listed as a treatment condition, but it is not the stated reference for the primary endpoint. The registry does not report a numerical contrast or identify the statistical model used to estimate it.

In general, a comparison may be expressed as a difference between means or by another scale, depending on the analysis plan and endpoint. The scale used for the primary treatment comparison is not reported in the registry record. It would be inappropriate to infer a ratio, a percentage change, or another comparison measure from the endpoint name alone.

What do uncertainty measures add?

In general, an estimate describes the observed contrast, while a confidence interval conveys its precision and the range of values reasonably compatible with the analysis. A p-value, when reported, assesses how compatible the data are with a specified null hypothesis under the statistical model; it does not measure the size or clinical importance of an effect. The registry does not report a primary comparison estimate, confidence interval, or p-value. Therefore, these inferential aspects cannot be evaluated from the registry record.

The mean and standard deviation are not substitutes for an interval around the treatment comparison. A standard deviation describes variability among observations, whereas uncertainty in a mean or contrast also depends on the amount and structure of available data and on the analysis method. The analysis sample size and statistical method are not reported in the registry record, so no precision calculation can be reconstructed from the stated endpoint summary type.

What design features affect the analysis?

The study is identified as non-randomized, unmasked, and single group. In general, random allocation helps balance measured and unmeasured prognostic factors across groups, while masking can limit expectation-related influences on measurement or conduct. Their absence does not by itself determine the direction of bias, but it affects the strength of causal interpretation. Here, the registry warns that the listed arms are not a like-for-like control comparison.

The treatment sequence and period structure are not reported in the registry record. In general, when participants receive multiple conditions over time, interpretation can depend on order, timing, and whether effects from an earlier condition carry into a later period. Those issues cannot be assessed without the actual schedule and analysis approach. This explanation is general and does not establish that any particular sequence or carryover effect occurred in this study.

What can the planning illustrations establish?

The registry’s planning assumptions describe illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not observed trial outcomes and not observed power. The numerical observed effect and the resulting planning figures are not reported in the registry record. Such illustrations cannot replace an estimate and uncertainty interval from the study’s actual primary analysis.

In general, a planning sample size depends on the effect size selected, variability, significance level, power target, allocation, and analysis assumptions. A planning result is conditional on those inputs; it does not show that a completed study had a particular probability of detecting an effect. No conclusion about the adequacy of the study’s enrollment can be made from the planning description alone. The registry does not report the trial’s own sample-size justification or the statistical analysis plan.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Maraviroc + Raltegravir (Test)", "Maraviroc (Reference)")
n   <- c(17, 17)
m   <- c(2551.9, 2971.6)
sp  <- c(786.68, 841.65)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Maraviroc + Raltegravir (Test)  17  2551.900  786.680  2147.426  2956.374
CARM  Maraviroc (Reference)  17  2971.600  841.650  2538.864  3404.336

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses. It does not report how these measures and analyses were organized into a testing hierarchy, whether any adjustment for multiple testing was planned or applied, or how the primary endpoint was protected from multiplicity. These details are not reported in the registry record. The number of listed outcomes alone does not establish that every outcome was tested in the same way or that all tests were confirmatory.

In general, testing multiple hypotheses can increase the chance of obtaining at least one apparently notable result by chance. Methods for addressing multiplicity depend on the scientific questions and analysis plan. Without the prespecified hierarchy, test procedures, or adjusted results, the impact of multiplicity on interpretation cannot be assessed. No claim about correction or lack of correction should be inferred from the registry’s listing of outcomes.

The record defines a pharmacokinetic analysis population as enrolled and treated subjects with at least one primary-interest pharmacokinetic parameter in at least one treatment period. The number included in this population is not reported in the registry record. The record also does not report the number with complete measurements for the primary comparison, the reasons for missing measurements, or the method used to handle missing data. It therefore cannot establish whether the primary comparison used all enrolled subjects or a smaller analytic set.

In general, missing-data methods rely on assumptions about why measurements are absent and how that absence relates to observed or unobserved values. Complete-case analysis, imputation, and model-based approaches can produce different results under different assumptions. The method used in this study is not reported in the registry record, so its consequences cannot be evaluated. The stated analysis-population definition should not be treated as a missing-data procedure.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts of 0 for maraviroc, 0 for maraviroc + raltegravir, and 0 for raltegravir. The corresponding serious-event groups at risk are listed as 18, 17, and 18. These are reported counts, not evidence that no non-serious events occurred. They also do not, by themselves, establish comparative safety across conditions, particularly given the non-randomized, single-group design.

Other adverse event counts are reported as 4 for maraviroc, 4 for maraviroc + raltegravir, and 3 for raltegravir. The number at risk for these other events is not reported in the registry record. Without those denominators and further definitions, these counts should not be read as rates or used to compare the frequency of events across treatment conditions. The registry does not provide the event terms for these other events in the registry record for this analysis.

Death counts and the denominators for other events are recorded as null, rather than as numerical values. A null entry is not the same as a reported count of zero; whether deaths occurred cannot be determined from that entry. No serious-event terms are listed. The safety information is therefore limited to the reported counts and group-at-risk figures, and does not support broader conclusions about the full adverse-event profile.

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

This study is designed to examine a pharmacokinetic interaction: the registry’s primary question concerns maraviroc AUCτ with raltegravir co-administration compared with maraviroc alone. It establishes the endpoint definition, unit, summary type, assessment days, and analysis-population definition. Those elements explain what the investigators intended to measure, but do not reveal what the measurement showed.

The primary numerical results are not reported in the registry record. Therefore, the direction and size of the observed comparison, its precision, and its statistical evidence cannot be described. The endpoint definition cannot be used to conclude that exposure changed, remained similar, or met any threshold. It also cannot establish a clinical consequence. Pharmacokinetic measurements describe exposure; interpreting their relevance requires the actual estimates and appropriate clinical context.

The record’s design information also matters. The study was open label, non-randomized, and single group, and the registry cautions that the treatment conditions are not a like-for-like control comparison. Although three treatment conditions are listed, the detailed schedule and order are not reported. The record does not establish how the comparison accounted for timing, treatment sequence, or other sources of variation. These limitations do not prove that the result is biased; they delimit what can be inferred from the design description.

The population was healthy subjects, so the record does not itself establish whether the pharmacokinetic findings apply to other populations. The number analyzed for the endpoint, handling of missing measurements, and analysis method are not reported in the registry record. The enrollment figure of 18 should not be interpreted as the number contributing complete data to every condition.

The safety entries report zero serious adverse events for each listed condition, alongside other adverse event counts whose at-risk denominators are not reported. Death entries are null. These data should be read narrowly and do not provide a complete safety comparison. Overall, the registry record documents the study question and selected design and safety information, but does not provide the numerical primary result needed to judge the magnitude or precision of the pharmacokinetic comparison.

14. Why This Trial Matters Statistically

Interaction studies address whether co-administration is associated with a change in drug exposure. AUCτ is relevant to that question because it summarizes concentration over a dosing interval rather than at a single time. The registry’s stated comparison—maraviroc with raltegravir versus maraviroc alone—therefore gives a focused pharmacokinetic question.

The study is also a useful example of why endpoint definitions and outcome results must be distinguished. The record specifies the measure, unit, summary statistic, assessment days, and analysis-population definition, yet does not report the numerical primary comparison. A reader can identify what was intended to be measured, but cannot assess the observed effect or its precision without the estimates and uncertainty measures.

Design labels are important to statistical interpretation. This study is listed as non-randomized, open label, and single group, and the registry cautions that the conditions are not a like-for-like control comparison. These features do not make a pharmacokinetic study uninformative, but they mean that the design and treatment schedule are essential context. In this record, the treatment sequence and detailed schedule are not reported, limiting assessment of how the conditions were compared.

The record further illustrates that enrollment and analytic contribution are not interchangeable. Although enrollment is 18, the number included in the defined pharmacokinetic analysis population and the handling of missing measurements are not reported in the registry record. Finally, serious-event counts are available, but other-event denominators and death counts are not. Statistical interpretation must therefore be calibrated to the specific information recorded rather than extending beyond it.

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 most important limitation for interpreting the primary question is that numerical AUCτ results are not reported in the registry record. Means, standard deviations, a treatment comparison, uncertainty intervals, and test results are absent. Without those quantities, the primary pharmacokinetic finding cannot be evaluated for direction, magnitude, or precision.

The design information is limited. The trial is identified as non-randomized, open label, and single group, and the registry warns that the listed conditions are not a like-for-like control comparison. Arm descriptions are blank. The treatment schedule, order of conditions, and any washout arrangements are not reported in the registry record. No assumptions about a crossover structure, sequence balance, or carryover control can be made from the available description.

The record reports enrollment of 18 but not the number contributing data to the primary comparison. It defines the pharmacokinetic analysis population, but does not state how many met that definition, whether measurements were complete across conditions, or how missing data were handled. The statistical model, comparison scale, and primary analysis procedure are also not reported in the registry record.

The study population is described as healthy subjects. The registry record does not establish how findings would apply to other populations. For safety, the serious-event counts and corresponding at-risk figures are reported, but the at-risk figures for other events and death counts are null. The available safety entries therefore do not provide a complete basis for comparing all adverse outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study To Evaluate An Interaction Between Maraviroc And Raltegravir In Healthy Subjects — NCT00666705.
• Registry record last updated 2013-01-25; status last verified 2013-01.
• Results first posted 2009-06-04.
• 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

NCT00666705 is a completed, open-label Phase 4 study sponsored by ViiV Healthcare. It enrolled 18 healthy subjects, used non-randomized allocation, and is listed as a single-group model. The recorded start is 2008-02 and primary completion is 2008-03.

The primary endpoint is maraviroc AUCτ, in ng.hr/mL, summarized as a mean with standard deviation. The stated comparison is maraviroc co-administered with raltegravir versus maraviroc alone. Pharmacokinetics were assessed on Day 11 for maraviroc and on Day 14 for maraviroc and raltegravir. Numerical primary results and the statistical analysis method are not reported in the registry record.

Serious adverse event counts are 0 for each listed condition. Other adverse event counts are 4, 4, and 3; their at-risk denominators are not reported. Death entries are null. The record lists six outcome measures and six analyses but does not describe a multiplicity procedure. It defines a pharmacokinetic analysis population, while the number included and the missing-data approach are not reported in the registry record.