The Maraviroc Darunavir/Ritonavir Once Daily Pharmacokinetic Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Maraviroc Darunavir/Ritonavir Once Daily Pharmacokinetic Study (NCT01348763), a na phase 1 study. The primary outcome is The Ratio of the Maximum Plasma Concentration of Maraviroc Between 20 and 10 Day.

2. Clinical Question

3. Trial Design

This was a phase 1, prospective, open-label, two-phase pharmacokinetic study. The registry identifies the design as single-group, with allocation recorded as not applicable and masking as none. These features mean that the registry does not describe random assignment or blinded treatment assessment. The record lists one group, described as taking Truvada, darunavir/ritonavir, and maraviroc.

Participants were described as taking Truvada and darunavir/ritonavir before study entry. The treatment sequence then added maraviroc on day 1 and stopped Truvada on day 11. The primary pharmacokinetic outcome refers to maximum plasma maraviroc concentrations measured on day 10 and day 20. This sequence makes the timing of each measurement important: the primary contrast is tied to different points in the treatment course, not to a concurrent randomized comparison.

The registry identifies HIV as the condition and lists maraviroc, Truvada, and darunavir as interventions. It names Imperial College London as sponsor and St. Mary's Hospital, London as the care setting in the brief study description. The study is recorded as completed, with start in 2011-10 and primary completion in 2012-02. Enrollment is recorded as 13.

Because the design is single-group and open label, interpretation depends on the within-study measurements and their timing. The record does not provide enough detail to establish the exact analysis set, whether the same participants contributed measurements at both times, or how incomplete measurements were handled. A separate control-group effect, randomization-based balance, and masking-related protection against assessment bias are not available as features of the described design.

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.

With Tenofovir/Emtricitabine (10 Days)

Reasons for not completing this period:

Without Tenofovir/Emtricitabine (11 Day)

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 The Ratio of the Maximum Plasma Concentration of Maraviroc Between 20 and 10 Day, measured over 10 day, 20 days.

The named primary endpoint is the ratio of maximum plasma maraviroc concentration between day 20 and day 10. Maximum plasma concentration is a pharmacokinetic measure of the highest measured drug concentration in plasma over the relevant sampling period. A comparison of this measure across study times can describe whether peak exposure differed during the treatment sequence. The registry specifies the outcome as a continuous measure summarized by a mean and a 95% confidence interval.

In general, a ratio expresses one quantity relative to another, which can make it useful for comparing measurements taken under different conditions or at different times. The endpoint title does not state which day is the numerator, however, and the detailed ratio formula is not reported in the registry record. The record also does not provide the concentration values, the estimated ratio, or the confidence interval. It is therefore not possible to describe the direction, magnitude, or precision of the observed relationship from the registry entry.

Peak concentration is one aspect of drug exposure; it is not by itself a complete account of exposure over time or of clinical outcomes. The stated endpoint is pharmacokinetic, and the record does not identify it as a measure of treatment benefit. Its role is to quantify a concentration comparison across the specified study times. Without the posted estimate and its uncertainty, the endpoint definition can be explained, but its empirical finding cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

The primary measure is identified as a continuous outcome with a mean as its summary. In general, a mean combines measured values into a central estimate on the outcome's scale. For a ratio endpoint, interpretation depends on precisely how the ratio is formed and what values enter the summary. The registry record does not describe the ratio calculation, the individual concentration measurements, or any transformation used in analysis. It is therefore possible to explain the stated summary, but not to reconstruct the estimator or verify how it was applied.

A mean can be informative when it represents the intended population quantity and when the data and analysis support that summary. It can also be affected by extreme observations, particularly when the distribution is asymmetric. Pharmacokinetic measurements can have distributional features that merit careful examination, but the record does not provide distributions, plots, medians, or diagnostic results. No claim about the observed distribution or the appropriateness of a particular model can be made from the registry entry.

How should a 95% confidence interval be read?

In general, a confidence interval expresses statistical uncertainty around an estimated quantity under a specified method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The interval is not a guarantee that the true value falls within its endpoints, and its interpretation depends on the sampling and analysis assumptions. The registry identifies a 95% confidence interval as the intended dispersion measure but does not report its endpoints or the method used to calculate it.

Without those endpoints, it is not possible to assess the interval's width, determine how it relates to a reference value, or compare its precision with another study. The interval cannot be inferred from enrollment alone. The number of analyzed measurements, their variability, the relationship between measurements, and the calculation method would all be relevant, and these details are not reported in the registry record.

What does a ratio compare?

In general, a ratio compares one quantity with another by expressing their relative scale. For this endpoint, the quantities are maximum plasma maraviroc concentrations measured on day 20 and day 10. But the title's wording does not establish the numerator and denominator order, and the record does not give the formula. That matters because reversing the order changes the direction of interpretation. No direction or magnitude should be inferred without the actual definition and estimate.

When measurements are collected from the same people at different times, an analysis may account for the relationship between a person's measurements. That is a general statistical consideration, not a description of the method used in this study. The registry record does not state whether the primary analysis was paired, how the repeated measurements were modeled, or whether all participants posted measurements at both times. It would be inappropriate to attribute any particular paired or repeated-measures method to the investigators.

What can the design establish?

The study is listed as single-group, prospective, and open label, with no allocation and no masking. In general, measurements over time in one group describe what was observed during the study sequence. Without a separately randomized comparator, the design does not provide a randomized between-group estimate. Changes across time may reflect the treatment sequence alongside other time-related or measurement-related influences. This is a design limitation, not evidence that any particular influence occurred.

The sequence includes maraviroc added on day 1 and Truvada stopped on day 11. The primary measurements are specified for day 10 and day 20. These details make the timing essential to understanding the endpoint, but the registry does not say whether other aspects of care, sampling, or participant circumstances were held constant. The result, if reported elsewhere, would need to be interpreted in the context of this sequence and the available analysis details.

What do the planning assumptions mean?

General planning illustrations are identified as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not a report of the study's original design rationale. They do not establish that the trial was designed with those assumptions, and they are not observed power.

The equal-allocation, two-arm framework does not match the registry's description of a single-group study. In this context, such an illustration should be understood as a hypothetical planning exercise rather than a calculation describing the actual design. The registry does not report a sample-size justification, a target power, or a protocol-based statistical plan. It also does not provide the observed primary effect needed to interpret a planning calculation in relation to this study.

In general, power is a property of a planned analysis under specified assumptions, not a measure of whether a completed study produced a useful result. Retrospective calculations based on an observed effect should not be interpreted as the probability that a finding is true. Here, the absence of a reported primary estimate means there is no registry result on which to base a quantitative interpretation of any effect-based planning illustration.

What analysis details remain unknown?

The registry record lists 0 analyses, but that listing does not establish what analyses were conducted outside the registry entry. No test statistic, p-value, model specification, covariate adjustment, missing-data procedure, or analysis population is reported. The endpoint's mean and confidence interval describe the intended form of summary, not a complete analysis plan. These gaps limit reproducibility and prevent an independent assessment of how the primary comparison was estimated.

For a continuous pharmacokinetic measure, methods should be interpreted in light of the scale, distribution, sampling structure, and missingness. Those are general considerations. The record does not provide enough information to determine whether the investigators used a normal-theory method, a transformation, a robust method, or another approach. No particular procedure should be attributed to the trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures, including the primary pharmacokinetic measure and a secondary outcome concerning participants with changes in haematology and biochemistry laboratory tests. It does not report a multiplicity adjustment, a hierarchy of testing, or another strategy for handling several outcomes. Without such information, the record does not establish how the chance of false-positive findings across multiple analyses was addressed. This does not show that no strategy existed; it means the strategy is not reported in the registry record.

The record lists 0 analyses and provides no numerical primary result. It does not report missing-data counts, reasons for missing measurements, imputation, or sensitivity analyses. Enrollment is recorded as 13, but the number contributing to each primary measurement is not stated. The analysis population is also not described; the primary outcome's population field is blank. Accordingly, it is not possible to tell whether the primary summary was based on all enrolled participants, those with measurements at both times, or another set.

In general, missingness can affect both the size and precision of an estimate, especially when the availability of measurements is related to participant characteristics or outcomes. This is a general concern, not a claim that missing data occurred in this study. The registry record does not permit an assessment of whether missingness was present or how it might have influenced the result.

The statistical planning assumptions describe a hypothetical two-arm, equal-allocation illustration using a two-sided significance level of 0.05 and a normal approximation. That framework does not describe the listed single-group study. Such planning figures are not observed power and should not be treated as evidence about the study's actual analysis or design. A protocol-based sample-size justification and a complete statistical analysis plan are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The safety record lists the group Truvada, darunavir/ritonavir, and maraviroc, with 11 participants at risk for the serious adverse event category and 0 affected. For the other adverse event category, it also lists 11 at risk and 0 affected. Deaths are recorded as 0, and no serious adverse event terms are listed. These are the registry's posted counts for the categories described; they should not be read as a complete account of every possible safety outcome.

In general, an observed count of 0 does not establish that an event is impossible or that a treatment is free of risk. The count describes what was recorded among those at risk in this study. The registry does not explain why the adverse-event at-risk count differs from the enrollment figure, and it does not provide additional detail about event definitions, surveillance duration, severity grading, or event collection methods. These details are not reported in the registry record.

The safety counts should also be interpreted in light of the study's single-group design and the short-term study description. Without a concurrent comparison group, the counts do not estimate a relative safety difference between regimens. They are descriptive registry entries, not evidence for a broader safety conclusion.

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

The study's stated purpose was to assess the steady-state pharmacokinetic profile and short-term safety of maraviroc given with darunavir/ritonavir, with and without nucleoside analogues, in HIV-1-infected subjects. The primary endpoint focused on a ratio of maximum plasma maraviroc concentration at day 20 and day 10. The treatment sequence and endpoint definition provide context for the question, but the registry record does not report the numerical primary result.

As a result, the posted record cannot establish the magnitude or direction of the concentration relationship, or how precisely it was estimated. The specified 95% confidence interval has no reported endpoints. The study's enrollment figure does not substitute for the missing effect estimate, and it cannot reveal the variability of the measurements or the number included in the primary analysis.

Even if a numerical pharmacokinetic result were available, it would answer a question about measured drug concentration under the study conditions. In general, a pharmacokinetic measure is not automatically a direct measure of clinical benefit, and a change in a concentration measure does not by itself establish a clinical outcome. This record does not report a clinical efficacy comparison.

The design also limits what can be concluded. A prospective, open-label, single-group study can describe measurements observed during its treatment sequence, but it does not provide a randomized comparison with another regimen. The sequence includes both the addition of maraviroc and the later discontinuation of Truvada. Any time-based interpretation would need to account for this context; the record does not isolate a causal effect of a single component.

The adverse-event entries report 0 affected in the listed serious and other event categories among 11 at risk, and 0 deaths. These counts are descriptive and do not establish the absence of risk beyond the observations recorded. Overall, the registry supports a description of the study question, design, and posted safety counts, but not a quantitative conclusion about the primary pharmacokinetic endpoint or a general clinical conclusion.

13. Why This Trial Matters Statistically

This trial is statistically notable because it frames a pharmacokinetic comparison across two specified study times within a single treatment sequence. The primary measure is a ratio of maximum plasma maraviroc concentration at day 20 and day 10, with a mean and 95% confidence interval identified as the planned summary. This gives readers a defined estimand in broad terms, while leaving important details—such as the ratio orientation and analysis method—not reported in the registry record.

The design illustrates why the structure of a study must shape interpretation. A prospective, open-label, single-group study can document measurements as treatment changes over time, but it does not offer the same basis for causal comparison as a randomized control group. The sequence matters: maraviroc is added on day 1, and Truvada is stopped on day 11. Statistical conclusions about the day 10 and day 20 measurements therefore need to be understood in relation to those regimen conditions.

The record also illustrates the difference between specifying an endpoint and reporting a result. It names the primary measure and its intended uncertainty summary, yet the numerical estimate and confidence interval are not reported. Without them, readers cannot evaluate magnitude or precision. Clear endpoint definitions are useful, but they do not replace the result and analysis details needed for quantitative interpretation.

Finally, the record highlights the need to distinguish study-specific analysis from hypothetical planning. The stated sample-size assumptions describe a two-arm planning illustration, while the trial is listed as single-group. Such a calculation is not evidence of the trial's original design rationale, nor is it observed power. Recognizing this distinction helps prevent planning quantities from being mistaken for results or design characteristics.

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 main limitation for interpreting the primary endpoint is that the registry record does not report its numerical estimate or 95% confidence interval. The ratio's exact numerator and denominator are also not specified in the endpoint description. Without the estimate, interval, or formula, neither direction nor precision can be evaluated.

The single-group, open-label design does not provide a randomized control comparison. The study sequence changes over time, with maraviroc added on day 1 and Truvada stopped on day 11. The day 10 and day 20 measurements therefore occur in different regimen contexts. The record does not establish how other time-related influences were addressed or whether the primary analysis accounts for within-participant measurement relationships.

Enrollment is recorded as 13, while the adverse-event categories list 11 at risk. The registry does not explain this difference. It also does not report the number of participants with primary measurements at each time, the analysis population, missing-data handling, or reasons for any unavailable measurements. The endpoint population field is blank, and the listed analysis count is 0. These omissions make it difficult to assess completeness and reproducibility.

Further details that could inform interpretation are not reported in the registry record, including the ratio calculation, analysis model, confidence-interval method, multiplicity strategy, and sample-size justification. The record describes the study as short-term and provides study dates, but does not detail the duration of safety surveillance or the procedures used to collect adverse events. The safety counts should therefore be understood as the posted registry entries, not as a comprehensive estimate of risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Maraviroc Darunavir/Ritonavir Once Daily Pharmacokinetic Study — NCT01348763.
• Registry record last updated 2019-10-31; status last verified 2019-10.
• Results first posted 2019-10-31.
• 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 NCT01348763, a completed phase 1, prospective, open-label, single-group pharmacokinetic study sponsored by Imperial College London. It lists HIV as the condition, enrollment of 13, start in 2011-10, and primary completion in 2012-02. Participants were described as taking Truvada and darunavir/ritonavir before study entry, adding maraviroc on day 1, and stopping Truvada on day 11.

The primary outcome concerns the ratio of maximum plasma maraviroc concentration between day 20 and day 10, with a mean and 95% confidence interval specified. The numerical result, confidence limits, exact ratio formula, and primary analysis population are not reported in the registry record. The record lists 2 outcome measures and 0 analyses.

For the listed safety group, the registry records 0 affected among 11 at risk in both serious and other adverse-event categories, and 0 deaths. No serious adverse event terms are listed. These counts are descriptive and do not provide a randomized comparison.