This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Raltegravir and Ribavirin Pharmacokinetics (PK) Study (NCT00982553), a non-randomized phase 1 study. The primary outcome is Ribavirin Maximum Plasma Concentration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00982553 |
| Phase | Phase 1 |
| Condition | HIV Infections |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers enrolled in a phase I pharmacokinetic study. The registry record reports enrollment of 14 participants and identifies the primary endpoint population as per protocol. It does not give further eligibility details or describe how many participants contributed to each analysis.
Intervention
Raltegravir and ribavirin were administered in separate phases and together. The record describes single-dose ribavirin (800 mg) on day 1, raltegravir (400 mg twice daily) from days 15-19, and ribavirin (800 mg) with raltegravir (400 mg) on day 20.
Comparator
The study was non-randomized and single-group, rather than a randomized comparison between concurrent groups. The separate-drug phases and the combined-drug phase form the pharmacokinetic context for examining blood levels; the registry record does not describe a randomized control arm.
Primary question
The stated purpose was to assess whether raltegravir and ribavirin affect each other’s blood levels when given separately and together. The listed primary endpoint is ribavirin maximum plasma concentration on day 20, assessed in the per-protocol population. Its numerical estimate and confidence interval are not reported in the registry record.
This is a pharmacokinetic question about drug concentrations, not a clinical-outcome comparison. The three-phase schedule places administration of each drug separately before their combined administration, allowing the study to assess concentration patterns across those phases. Because the allocation is non-randomized and the design is single-group, the phases should not be interpreted as independent, randomized treatment arms. The record does not describe the detailed statistical contrast used to assess whether the drugs affected one another’s levels.
The study is listed under HIV infections and its brief summary describes raltegravir as an anti-HIV drug and ribavirin as an anti-hepatitis C drug. Its stated aim, however, is pharmacokinetics and safety in healthy volunteers. The registry record does not report an efficacy question about treating either infection.
3. Trial Design
The registry record describes a prospective, open-label, three-phase pharmacokinetic study, classified as phase I. It lists Imperial College London as sponsor, a non-randomized allocation, no masking, and a single-group model. Enrollment was 14. The study status is completed; the recorded start was 2009-09 and primary completion was 2009-11.
The phase descriptions specify single-dose ribavirin (800 mg) on day 1, raltegravir (400 mg twice daily) from days 15-19, and ribavirin (800 mg) with raltegravir (400 mg) on day 20. These descriptions establish the order and scheduled dosing stated in the registry record. Further operational details, including the timing and frequency of blood sampling beyond the endpoint timeframe, are not reported in the registry record.
Open-label means the record does not describe masking of treatment; it lists masking as none. Non-randomized allocation means that random assignment is not the basis for the listed sequence. The design is not a like-for-like comparison of randomized arms. Instead, the phases provide the setting for evaluating pharmacokinetic measurements when drugs are given separately and together. The record does not state whether every participant completed every phase, or how deviations from the scheduled phases were handled.
The listed primary outcome is ribavirin maximum plasma concentration, measured in ng/mL on day 20, with a geometric mean and 95% confidence interval specified as the summary format. The primary population is per protocol. The record lists four outcome measures and four analyses, but does not name the additional measures or explain how each analysis relates to them. A detailed protocol, statistical analysis plan, sample-size justification, and prespecified decision criteria are not reported in the registry record.
With a single-group, non-randomized sequence, interpretation depends on the measurements and analysis specified for the phases. The registry record does not establish a concurrent untreated group or a randomized comparison. It also does not give details about participant characteristics, eligibility criteria, or the handling of possible period or sequence effects. Those omissions limit how fully the design can be reconstructed from the record alone.
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 healthy volunteers. * There was a 21 day washout for any prescribed and 7 days for over the counter medication before enrolment. * The subjects were permitted to take paracetamol during the study but all others were excluded for the duration of the trial.
Phase1
| Stage | All Subjects |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
Phase2
| Stage | All Subjects |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
Phase3
| Stage | All Subjects |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Per protocol
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.
| Characteristic | Unit | All Subjects |
|---|---|---|
| Participants analysed | 14 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 35 (SD 10) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 10 |
| Region of Enrollment: United Kingdom | participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Ribavirin Maximum Plasma Concentration, measured over Day 20.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is ribavirin maximum plasma concentration on day 20, expressed in ng/mL. Day 20 is the described phase in which ribavirin and raltegravir are administered together. Maximum plasma concentration is a pharmacokinetic measure: it represents the highest measured concentration of a drug in plasma over the relevant sampling period. Such a measure can help characterize drug exposure and is used in pharmacokinetic studies to examine how concentrations may differ across administration conditions.
The registry record specifies a geometric mean and a 95% confidence interval as the summary format, and identifies the per-protocol population. A geometric mean is commonly used for positive concentration measurements when their distribution is skewed; it summarizes values on a multiplicative scale rather than as an arithmetic average. A confidence interval expresses uncertainty around an estimated quantity, subject to the statistical model and data used. These are general descriptions of the statistical concepts, not additional claims about the analysis performed in this study.
The endpoint can describe ribavirin concentration during the combined-drug phase, but its interpretation as evidence about an interaction depends on the comparison and analysis used. The registry record does not give the numerical geometric mean, confidence interval limits, exact sampling schedule, or a detailed definition of how the maximum was selected. The primary endpoint result is therefore not reported in the registry record. The listed measure alone cannot establish the size or direction of any change in concentration.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a specific pharmacokinetic endpoint: ribavirin maximum plasma concentration on day 20, when ribavirin and raltegravir were scheduled together. It also specifies that the endpoint is summarized as a geometric mean with a 95% confidence interval in a per-protocol population. However, the numerical estimate and confidence interval are not reported in the registry record. Without those values, the concentration observed in the combined-drug phase and its precision cannot be described.
The study’s stated purpose concerns whether the drugs affect each other’s blood levels. Answering that question requires more than knowing that a combined phase and separate phases were scheduled. Interpretation would depend on the concentrations measured in each condition, the comparison defined by the analysis, and the uncertainty around that comparison. Those results and details are not reported in the registry record. It is not possible to state whether concentrations were higher, lower, or similar across the phases.
The design is non-randomized and single-group. Consequently, its phases should not be described as randomized, concurrent treatment groups. Measurements across phases can be informative about pharmacokinetics, but changes across time may be difficult to distinguish from changes associated with the dosing condition unless the analysis and design address relevant sources of variation. The registry record does not report how period, sequence, or other possible influences were evaluated. This is a limitation on interpretation, not evidence that such influences occurred.
The confidence interval named in the endpoint description would convey precision around the geometric mean if its limits were available. A narrow interval would generally indicate a more precise estimate than a wide interval, while neither width alone nor the interval’s position answers every scientific question. Here, neither the interval nor the estimate is reported in the registry record, so no judgment about precision can be made. No hypothesis test result for the primary endpoint is stated.
The record lists four outcome measures and four analyses, but the additional outcomes and their numerical findings are not reported in the registry record. This prevents a fuller account of whether other pharmacokinetic measures support, qualify, or differ from the primary endpoint. The safety fields report zero serious adverse events and zero other adverse events affected among 14 subjects at risk in each category. Those entries describe the registry’s reported counts; they do not provide a detailed account of event definitions, collection procedures, or the nature of all possible symptoms.
Overall, the record establishes the study’s question, dosing sequence, endpoint type, and broad design. It does not report the numerical pharmacokinetic result needed to quantify an interaction, nor the detailed analysis needed to assess the comparison. Conclusions should therefore remain limited to what the record describes: a completed phase I study designed to assess pharmacokinetics and safety when raltegravir and ribavirin were given separately and together.
9. Statistical Methods Explained
Pharmacokinetic studies describe how drug concentrations change over time under specified dosing conditions. In this study, the registry record describes separate administration phases and a phase in which ribavirin and raltegravir were administered together. Blood samples were used for pharmacokinetic analyses. The record does not specify the full sampling schedule, sample handling, or the mathematical methods used to derive each outcome.
What does maximum plasma concentration represent?
Maximum plasma concentration, often called peak concentration in general pharmacokinetic language, is a measure of the highest observed concentration over a defined sampling period. It is distinct from total exposure over time, the time to reach a peak, and the concentration at a particular sampling time. These measures answer different questions. The registry record names maximum plasma concentration as the primary endpoint for ribavirin on day 20, but does not report the concentration value or define the exact sampling window used to identify the maximum.
Concentration measurements are generally positive and may be right-skewed, with some observations considerably larger than others. For that reason, pharmacokinetic summaries often use logarithmic transformations or geometric summaries. This is general statistical context; the registry record identifies a geometric mean but does not specify the estimation procedure, the transformation, or the model.
Why use a geometric mean?
A geometric mean summarizes positive values on a multiplicative scale. Conceptually, it reflects the central value after taking logarithms of the measurements and then transforming back to the original scale. This can be useful when proportional differences are more meaningful than absolute differences, or when values are skewed. It should not be interpreted as the arithmetic average. The endpoint description reports a geometric mean and a 95% confidence interval, but does not provide their values.
A confidence interval is a range calculated by a statistical procedure to express uncertainty around an estimate. Its interpretation relies on the method and assumptions used. In general, it gives information about precision rather than a guarantee that the true value lies within the particular observed range. The record’s stated 95% confidence level does not, by itself, reveal the interval’s width or whether the data provide a precise estimate. Since the interval limits are not reported in the registry record, its precision cannot be assessed.
How should the three phases be understood?
The record describes ribavirin alone on day 1, raltegravir from days 15-19, and both drugs on day 20. This schedule gives the pharmacokinetic question a within-study sequence of dosing conditions. It does not make the phases randomized arms, because allocation is listed as non-randomized and the model as single-group. A reader should distinguish a sequence of conditions from a randomized, concurrent comparison.
In general, repeated measurements from the same participants can allow comparisons that account for stable participant characteristics, if the analysis is designed to do so. However, the registry record does not state whether the primary analysis used paired measurements, a particular model, or any adjustment. Nor does it report whether the same participants contributed data at each phase. These details should not be inferred from the phase descriptions alone.
When conditions occur at different times, period and sequence effects can matter in principle. For example, concentrations may vary with timing, adherence, or other changes over the course of a study. This is a general consideration, not a claim that such effects occurred. The registry record does not describe tests or adjustments for these possibilities, washout procedures, or the rationale for the spacing between phases.
What does the per-protocol population mean?
A per-protocol analysis generally includes participants who meet specified requirements for completing the planned study procedures. The exact criteria can vary by protocol. The registry record labels the primary endpoint population as per protocol but does not define the criteria, state how many participants were included in that analysis, or explain the handling of participants who did not follow the schedule. Enrollment of 14 should therefore not be assumed to equal the primary analysis denominator.
The record names four outcome measures and four analyses, but does not list their identities or analytical specifications. The statistical plan, including any model, adjustment, hypothesis test, or treatment of missing observations, is not reported in the registry record. The endpoint’s summary format should not be mistaken for a complete description of the analysis method.
The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. These illustrations are not a description of the study’s own design: the actual study is single-group and non-randomized, and its sample-size justification is not reported in the registry record. Such planning values are not observed power and do not establish the study’s precision or ability to detect an effect. No numerical planning results are.
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If present, it can make standard errors and confidence intervals based on a simpler model too small. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model or information that would establish whether this issue arose in these data.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures and four analyses, but does not identify the additional outcomes, specify which analyses were primary or secondary, or describe the relationship between the outcomes and analyses. The named primary endpoint is ribavirin maximum plasma concentration on day 20. A multiplicity strategy, such as a prespecified adjustment across multiple tests or a hierarchy of outcomes, is not reported in the registry record. It is therefore not possible to determine how the study handled the chance of false-positive findings across multiple analyses.
Missing-data methods are also not reported in the registry record. The record does not state whether any measurements were missing, how missing concentration samples were handled, or whether any sensitivity analyses were conducted. The listed per-protocol population does not by itself explain exclusions or missingness. Enrollment was 14, but the number included in each outcome analysis is not reported in the registry record.
The record does not explain how participants who missed a phase, deviated from dosing, or lacked usable samples were treated. It also does not provide a participant flow description or analysis population definitions beyond the primary endpoint’s per-protocol label. As a result, the extent to which analyzed participants may differ from all enrolled participants cannot be assessed.
These omissions matter because multiplicity and missing observations can affect the interpretation of estimates and tests. They do not establish that the analysis was incorrect or that data were missing; they mean the registry record does not provide enough detail to assess those issues. No statistical analysis plan or prespecified missing-data approach is reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Subjects | 0 | 14 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| All Subjects | 0 of 14 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Subjects | 0 of 14 |
The safety record lists All Subjects, with 14 at risk for serious adverse events and 0 affected. It also lists 14 at risk for other adverse events and 0 affected. Deaths are recorded as 0. These counts describe the registry entries for this study; they are not a detailed account of event types, severity grades, timing, or the method used to collect safety information.
A serious adverse event is a category used in clinical research to capture events meeting specified seriousness criteria. The registry record does not provide those criteria or list serious-event terms. It also does not describe how non-serious events were defined or whether all events were actively solicited. The reported zero counts should therefore be read as the recorded counts in the specified categories, not as evidence that every possible symptom was assessed or that no event of any kind occurred.
The listed denominator is 14 at risk in each safety category. The record does not provide additional detail on duration of exposure, completeness of follow-up, or safety analysis methods. These counts are descriptive and do not establish a comparative safety profile, especially because the study is single-group and non-randomized.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a completed phase I, open-label, non-randomized, single-group pharmacokinetic study in healthy volunteers. It describes separate administration of ribavirin and raltegravir, followed by a combined phase, and states that the study’s purpose was to examine whether the drugs affect each other’s blood levels. The primary endpoint is ribavirin maximum plasma concentration on day 20.
What the record does not establish is the size or direction of any change in concentration. Although it names the geometric mean and 95% confidence interval as the endpoint summary, their numerical values are not reported in the registry record. The primary result is therefore not reported in the registry record, and its precision cannot be assessed. The registry also does not report the detailed comparison, statistical model, or results for the other listed outcomes.
The findings should not be framed as evidence about whether either drug treats an infection or improves a clinical outcome. The stated focus is pharmacokinetics and safety, and the participants are described as healthy volunteers. The record does not report clinical efficacy outcomes. Nor does a concentration measure alone determine clinical significance; that would require evidence and context beyond the endpoint description.
The study’s design also constrains interpretation. Its phases are non-randomized conditions in a single group, not randomized concurrent arms. The record does not explain how time-related influences or differences in analysis populations were handled. These are reasons to avoid overstating what the design can show, not grounds for assuming a particular bias or result.
In short, the available record supports a description of the question, schedule, design, endpoint, and reported safety counts. It does not support a quantitative conclusion about a pharmacokinetic interaction. Any interpretation of an effect or its practical importance would require the numerical outcome results and more detailed analysis information, neither of which is reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable for asking a pharmacokinetic interaction question through a non-randomized, single-group sequence rather than a randomized comparison between concurrent arms. That distinction affects what a reader can attribute to the drug conditions. A sequence of separate and combined administration can organize concentration measurements, but interpretation depends on the measurements, timing, and analysis—not simply on the fact that the phases occurred in that order.
The primary endpoint is a concentration summary, not a clinical outcome. Geometric means and confidence intervals are familiar tools for describing pharmacokinetic data, especially when positive measurements are analyzed on a multiplicative scale. In this record, the summary format is identified, but the estimate and interval are not reported. This illustrates an important distinction between specifying an endpoint and reporting a result: the endpoint definition tells readers what was intended to be measured, while the numerical result is needed to assess magnitude and precision.
The per-protocol label also highlights the importance of defining analysis populations. Enrollment is reported, but the record does not state the number included in the endpoint analysis or the criteria for per-protocol inclusion. Without that detail, readers cannot connect enrollment directly to the precision of the primary estimate.
Finally, the record lists multiple outcomes and analyses without identifying them or describing how multiple testing was addressed. Statistical interpretation depends not only on the endpoint but also on the full analysis plan and transparent reporting. This study therefore illustrates why design labels, endpoint definitions, analysis populations, uncertainty intervals, and complete numerical findings all matter when evaluating a pharmacokinetic study.
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 registry record does not report the numerical primary endpoint result, including the geometric mean and 95% confidence interval. Without those values, neither the concentration level nor its precision can be evaluated. The detailed results for the other listed outcomes are also not reported in the registry record, despite the record listing four outcome measures and four analyses.
The design is non-randomized and single-group, with phases conducted in a stated sequence. The record does not describe a randomized control group or explain how period and sequence considerations were addressed. It also does not report the precise statistical contrast used to assess whether the drugs affected one another’s levels. These gaps prevent a full assessment of how the planned comparison was implemented.
Additional design and analysis details are not reported in the registry record, including participant eligibility criteria, the number analyzed for the primary endpoint, per-protocol criteria, full blood-sampling schedule, handling of missing measurements, and any sensitivity analyses. The record does not provide a sample-size justification or a detailed statistical analysis plan. It is not possible to determine from the available information whether these details were absent from the study conduct or simply not included in the registry record.
Safety reporting is limited to the recorded counts for serious adverse events, other adverse events, and deaths. Event definitions, collection methods, exposure duration, and detailed event descriptions are not reported in the registry record. The safety counts should therefore be interpreted narrowly as recorded counts, rather than as a comprehensive characterization of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Raltegravir and Ribavirin Pharmacokinetics (PK) Study — NCT00982553.
- Registry record last updated 2019-10-11; status last verified 2019-09.
- Results first posted 2011-06-13.
- 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.
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18. Record Summary
NCT00982553 is a completed phase I, prospective, open-label pharmacokinetic study sponsored by Imperial College London. It enrolled 14 healthy volunteers and is listed as non-randomized and single-group. The recorded start was 2009-09, with primary completion in 2009-11.
The schedule describes ribavirin (800 mg) on day 1, raltegravir (400 mg twice daily) from days 15-19, and both drugs on day 20. The primary endpoint is ribavirin maximum plasma concentration in ng/mL on day 20, summarized as a geometric mean with a 95% confidence interval in the per-protocol population. The numerical endpoint result is not reported in the registry record.
The safety entries report 0 serious adverse events, 0 other adverse events affected, and 0 deaths among 14 subjects at risk in the listed categories. The record lists four outcome measures and four analyses; further outcome results and detailed statistical methods are not reported in the registry record.