Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants (NCT04371380), a na phase 1 study. The primary outcome is Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection.

2. Clinical Question

The question is pharmacokinetic and descriptive: it concerns measured drug concentrations over time in healthy adults, rather than comparative clinical benefit. The listed primary outcome is cabotegravir maximum observed concentration, or Cmax. Its sampling schedule begins on Day 1 and continues through week 52. The registry record does not report a numerical Cmax result, so the magnitude and precision of the observed concentration cannot be assessed from the posted outcome information. It also does not report a comparator-based estimate. The study can therefore be understood as an early investigation of drug exposure and tolerability under the described regimen, but the posted information does not establish how those measurements compare with another regimen or population.

3. Trial Design

This is a phase 1, open-label, single-group study. The registry record reports enrollment of 15 healthy adults and status as completed. It lists ViiV Healthcare as sponsor. Because there is one group and no randomized allocation, the design does not create a concurrent control comparison. Participants and study personnel were not masked, as the record identifies masking as none.

The described sequence includes an oral lead-in phase, a washout, an injection phase, and follow-up. During the oral lead-in, participants were to receive cabotegravir 30 mg and rilpivirine 25 mg once daily with a meal from Day 1 to Day 28. The description specifies a washout period of 10 to 14 days after that phase. Participants then received long-acting injections: cabotegravir 600 mg and rilpivirine 900 mg, administered intramuscularly into separate vastus lateralis muscles. Follow-up was planned for up to 52 weeks. The registry record gives a screening phase of 30 days and describes the study as assessing pharmacokinetics, tolerability, and safety.

These design features shape what can be learned. Repeated blood sampling supports description of concentration over time in participants with evaluable pharmacokinetic measurements. The absence of a control group means that changes cannot be separated from time, study participation, or other influences through a controlled contrast. The open-label design also means the record does not describe blinded assessment. A detailed statistical analysis plan, sample-size justification, interim analysis plan, and methods for handling protocol deviations are not reported in the registry record.

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: Fifteen participants were enrolled in the study. All the 15 participants received treatment in Oral Lead-in Phase. 14 out of 15 participants received treatment in Injection Phase. All the 14 participants in Injection phase completed the follow up phase.

Oral Lead-in Phase (Up to Day 28)

Reasons for not completing this period:

Injection Phase (IP)-Day 1[IP] to Week 4

Follow-up Phase (Week 4 to Week 52)

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter population included all participants who underwent plasma PK sampling and have evaluable PK parameters estimated.

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.

Population: All enrolled population included participants who signed the informed consent form and received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection, measured over Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52.

The primary outcome is the maximum observed concentration of cabotegravir, abbreviated Cmax, after a single intramuscular injection. It is expressed in micrograms per milliliter and summarized using a geometric mean with geometric coefficient of variation as the dispersion measure. Blood samples were scheduled from pre-dose and several post-dose time points on Day 1 through Day 52 weeks, with specified collection through week 52.

Cmax is a pharmacokinetic measure: it describes the highest observed plasma concentration over the sampling schedule, rather than a clinical outcome or a measure of treatment effect. It is used to characterize drug exposure after administration. General statistical context: concentration data are often positive and can vary multiplicatively, so geometric summaries may be useful when describing their central tendency and relative spread. That general rationale does not establish the distribution of concentrations in this study.

The record states that the pharmacokinetic population includes participants with plasma sampling and evaluable pharmacokinetic parameters. It does not report the numerical Cmax estimate, its geometric coefficient of variation, a confidence interval, or the number of participants contributing to this endpoint. Those omissions prevent assessment of the observed concentration’s magnitude and precision from the posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the geometric mean describe?

The primary endpoint is summarized with a geometric mean. General statistical explanation: an arithmetic mean describes an average on the original measurement scale, whereas a geometric mean is based on multiplicative relationships and is commonly used for positive measurements that may be right-skewed. It can be interpreted as a central value on a multiplicative scale. The endpoint is plasma concentration, which is positive when measurable, but the registry record does not report the observed values or describe their distribution. The choice of geometric mean alone does not show that a particular distributional assumption was tested or met.

The record also names the geometric coefficient of variation as the dispersion measure. General explanation: a coefficient of variation expresses spread relative to a typical value, and a geometric version is suited to summaries formed on a multiplicative scale. It helps convey variability in relative rather than absolute concentration units. No numerical value for this measure is reported for the primary endpoint, so the degree of observed variability cannot be assessed from the registry record.

What does Cmax represent?

Cmax is the maximum observed concentration of cabotegravir in plasma over the scheduled sampling times. It is not the average concentration across all visits, and it is not itself a measure of clinical benefit. The sampling schedule includes pre-dose and post-dose collection on Day 1, additional collections over subsequent days, and visits extending through week 52. The observed maximum depends on the values captured at those scheduled times; concentrations between collections are not directly described by the endpoint definition.

General statistical context: repeated concentration measurements can describe the time course of exposure, while a maximum-value summary reduces that sequence to one measure for each evaluable participant. That summary can be sensitive to when samples are collected and to whether measurements are available at relevant times. The registry record specifies the schedule but does not report participant-level concentration data or a numerical estimate of Cmax.

What does a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the statistical method used. It can help distinguish a relatively precise estimate from one compatible with a wider range of values. The registry record does not report a confidence interval for Cmax or describe an interval-estimation method. Thus, the precision of the primary estimate is not available for interpretation.

A confidence interval would not by itself answer a comparative question unless the estimand and comparison were defined. This study has no separate comparator group, and no comparative effect estimate is reported. The planned geometric mean is a description of concentration in the evaluable pharmacokinetic population, not a randomized treatment contrast.

What can be inferred from the analysis information?

The record describes the pharmacokinetic population as participants who underwent plasma sampling and had evaluable pharmacokinetic parameters estimated. That definition indicates that endpoint availability depends on both sampling and evaluability. The record does not state how many participants met those conditions, how missing samples were handled, or what criteria made a parameter evaluable. It also does not report whether analyses were adjusted for any covariates or which software or estimation procedures were used.

No statistical analysis outputs are listed in the registry record. A detailed statistical plan, including any planned hypothesis tests, estimation procedures, or interim analyses, is not reported in the registry record. It would therefore be inappropriate to infer a model or test from the endpoint’s summary measure alone.

How should planning calculations be understood?

General statistical explanation: sample-size calculations are planning tools based on assumptions about the effect to detect, variability, design, and error rates. They are not results from participants and do not show the probability that a study’s observed result is correct. The registry description characterizes its planning illustration as based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. Those are illustration assumptions, not evidence that this single-group study used a two-arm design.

The record does not report a study-specific sample-size justification or identify those planning calculations as the protocol’s design basis. In particular, planning values should not be called observed power. Without a reported primary endpoint estimate and uncertainty, those illustrations do not supply the missing result or establish precision for this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures, including the primary cabotegravir Cmax measure and secondary outcomes concerning liver-related adverse events and abnormalities. It does not report a multiplicity strategy, such as whether outcomes were organized into a testing hierarchy or whether any adjustment was planned for multiple statistical tests. It would be incorrect to assume either that an adjustment was made or that no adjustment was used in analyses beyond what is recorded.

No analysis outputs are listed. A statistical analysis plan, including the planned handling of multiple outcomes, interim analyses, or subgroup analyses, is not reported in the registry record. Without that information, the inferential status of any potential secondary result cannot be assessed from the record.

The record defines the pharmacokinetic population by sampling and evaluability, but does not report the number included in that population or explain the treatment of missing samples and unevaluable parameters. It also does not describe missing-data assumptions, imputation procedures, or sensitivity analyses. These details matter because the endpoint relies on measurements at scheduled times, and incomplete sampling could affect which participants contribute to an estimate. This is a general statistical concern, not evidence that data were missing or that a particular method was used.

The safety figures are phase-specific counts of participants affected. The registry record does not describe a missing-data method for safety reporting or provide enough detail to evaluate exposure-adjusted comparisons. The different phases should not be treated as independent trial arms. These reporting gaps limit assessment of how complete the analyses were and how uncertainty was handled.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports zero participants with serious adverse events in each listed phase. It reports 15 participants at risk during the oral lead-in phase, with 3 participants affected by other adverse events; 14 at risk during the injection phase, with 14 affected by other adverse events; and 14 at risk during follow-up, with 2 affected by other adverse events. No deaths are reported in the listed phases.

These are phase-specific participant counts. The count for other adverse events refers to participants affected, not the total number of adverse events, and the same participant may contribute to more than one phase. Because the phases are sequential parts of a single-group study, the counts are not a randomized comparison between independent groups. They do not establish that the risk differed between phases or that an injection caused an event.

The registry record does not list serious adverse-event terms, and the absence of reported serious events in these counts should be interpreted within the size and follow-up of this study. These figures do not establish the frequency of uncommon events beyond the participants observed. The record does not provide a comparative safety estimate or a detailed description of event severity, timing, or relatedness.

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

This study’s central statistical contribution, as described in the registry, is the assessment of drug concentrations after long-acting intramuscular administration in healthy adults. The endpoint definition and sampling schedule identify what the investigators intended to measure. The record also reports phase-specific counts of participants affected by serious and other adverse events.

What the posted result does not include is the numerical estimate for the primary Cmax endpoint. It therefore does not show the concentration value, the observed geometric variability, or the precision of the estimate. No confidence interval or primary endpoint analysis output is reported. Without those quantities, readers cannot assess the magnitude of the measured exposure from the registry record.

The design also limits interpretation. The study is single-group, open-label, and not a randomized comparison. It has no separate control group against which to estimate a difference. It enrolled healthy adults, so the record does not describe results in people with HIV infection or another clinical population. The stated objective includes tolerability and safety, but the posted counts alone do not constitute a controlled comparison or establish causal attribution.

General statistical point: descriptive estimates can be informative even without a comparator, but their meaning is tied to the participants, regimen, measurement schedule, and analysis population. They should not be extended automatically to other settings. Here, the registry record establishes the study’s design and intended pharmacokinetic measure, but does not report the primary numerical result needed to characterize the observed concentration quantitatively.

The study should therefore be read as an early, descriptive investigation rather than a test of comparative clinical effectiveness. The absence of a posted numerical endpoint result is not evidence that the endpoint was zero, nor does it imply a particular result. It means that the result is not reported in the registry record.

13. Why This Trial Matters Statistically

Pharmacokinetic studies use measured drug concentrations to characterize exposure after administration. This study’s primary endpoint, cabotegravir Cmax, reduces a series of scheduled plasma measurements to a maximum observed concentration. The record’s schedule extends from the dosing day through week 52, allowing the planned collection of information across early and later follow-up. That makes the endpoint and its timing central to understanding the study’s statistical question.

The design also illustrates why study structure matters when interpreting data. A single-group study can describe measurements in its participants, but without a control group it does not estimate a treatment difference. The open-label design and healthy-adult population further define the context in which the observations were to be made. These are not merely technical details: they determine which conclusions the design can support.

Precision is equally important. A geometric mean is named for the primary concentration outcome, but no numerical estimate or dispersion result is reported. Without the estimate and its uncertainty, readers cannot judge how precisely the concentration was characterized. This makes complete reporting of endpoint results important alongside a clear description of the endpoint and population.

The phase-specific adverse-event counts show another statistical distinction: sequential phases in one study are not equivalent to independent randomized groups. A numerical difference between phase counts would not, by itself, establish a difference in risk. The record’s structure and reporting therefore matter as much as the counts themselves.

Overall, the study is useful for illustrating the boundary between a well-defined pharmacokinetic question and the evidence needed to quantify its answer. The registry record describes the intervention, population, sampling plan, and outcome, but does not report the primary endpoint estimate. That distinction helps readers assess what can be learned from a study record without substituting assumptions for results.

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 principal limitation for statistical interpretation is that the registry record does not report a numerical result for the primary Cmax endpoint. It also does not report the geometric coefficient of variation, a confidence interval, or the number of participants included in the pharmacokinetic analysis. The concentration result’s magnitude and precision therefore cannot be assessed from the posted outcome information.

The study enrolled 15 participants and used a single-group, open-label design. There is no concurrent control group or randomized treatment contrast. Accordingly, the design does not support a controlled comparison with another regimen. Its population is described as healthy adults, which limits direct interpretation for other populations.

The record defines the pharmacokinetic population by sampling and evaluability but does not state the number meeting that definition or explain how missing samples and unevaluable parameters were handled. It does not report a detailed statistical analysis plan, multiplicity approach, interim analysis plan, or sample-size justification. These methods are not reported in the registry record, so they cannot be reconstructed from the endpoint description.

Safety reporting is presented as phase-specific counts. The record does not provide a comparative safety estimate or details sufficient to evaluate exposure-adjusted event rates, event timing, or relatedness. Because phases are sequential, their counts should not be treated as results from independent groups. These limitations concern what can be concluded from the registry record and do not establish that any particular analysis or information was absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants — NCT04371380.
• Registry record last updated 2024-04-22; status last verified 2023-11.
• Results first posted 2024-04-22.
• 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 NCT04371380 as a completed phase 1, open-label, single-group study of long-acting cabotegravir and rilpivirine intramuscular injections in healthy adults. Enrollment was 15. Participants were described as receiving an oral lead-in, a washout period, injections into separate vastus lateralis muscles, and follow-up planned for up to 52 weeks.

The primary outcome is cabotegravir maximum observed plasma concentration, summarized by a geometric mean with geometric coefficient of variation. The record specifies sampling through week 52 but does not report the numerical primary endpoint result or its precision. Phase-specific safety counts report zero participants with serious adverse events and varying counts with other adverse events. The record does not report a comparator-based analysis or detailed statistical analysis plan.