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 Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants (NCT04484337), a randomized phase 1 study. The primary outcome is Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04484337 |
| Phase | Phase 1 |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Sequential |
| Masking | Double |
| Enrollment | 138 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ViiV Healthcare |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy adult participants. Although HIV infections are listed as a condition, the brief summary describes the participants as healthy adults; the registry record does not describe this as a treatment trial in people living with HIV. The primary pharmacokinetic population was defined using treatment receipt and availability of at least one non-missing pharmacokinetic assessment.
Intervention
The study examined repeat-dose long-acting cabotegravir (CAB) injections using 400 mg/mL and 200 mg/mL formulations. Injection routes and sites included intramuscular administration in the gluteus medius or lateral thigh and subcutaneous administration in the abdomen. Some cohorts also examined topical treatments or recombinant human hyaluronidase PH20. Participants first received an oral CAB lead-in.
Comparator
The study is described as active-control and randomized, with CAB 400 mg/mL and CAB 200 mg/mL groups across several cohorts. Routes, injection sites, doses, and additional topical or hyaluronidase treatments varied. The registry record does not identify a single comparator that applies across the study, so the comparison depends on the cohort and outcome.
Primary question
The primary endpoint was the time of maximum observed plasma concentration (Tmax) after the first CAB 400 mg/mL injection, from Day 1 to Week 4, in Part 1 cohorts 1, 2, 3, 4, 4b, and 4h. This describes when the observed concentration peak occurred. The registry record does not report the numerical results for this endpoint, so it cannot establish from the posted record how Tmax differed across the included groups.
3. Trial Design
This was a Phase 1, randomized, double-blind, active-control study described as having a sequential model. The registry record gives an enrollment of 138 and lists the study as completed. The listed study start was 2020-07-31, and the primary completion date was 2023-05-05. These design features describe how the study was organized; they do not by themselves establish the precision or interpretation of an outcome estimate.
The study had two parts. In the oral lead-in, participants received oral CAB 30 mg once daily for Days 1 to 28. Part 1 investigated multiple injection regimens, including CAB 400 mg/mL and CAB 200 mg/mL given intramuscularly or subcutaneously. Cohorts differed in injection site and dosing schedule. Some groups also received topical NSAID or steroid treatments, placebo topical treatments, or CAB with recombinant human hyaluronidase PH20. The registry record’s arm descriptions are not complete for every regimen, so details beyond their stated content should not be inferred.
Part 2, Cohort 5, compared intramuscular gluteal injections of CAB 400 mg/mL and CAB 200 mg/mL, with injections approximately 12 weeks apart. The stated doses were 800 mg for CAB 400 mg/mL and 400 mg for CAB 200 mg/mL.
The primary endpoint concerns Part 1 only and is not a general measure of safety or clinical benefit. The registry record does not report the randomization sequence, allocation concealment, the rationale for the sequential design, or a detailed statistical plan. It also does not report the specific masking procedures. Those aspects should not be inferred from the labels randomized and double-blind.
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: This study consisted of an Oral Lead In (OLI) Phase (day 1 to 28), an Injection Phase, which consisted of part 1 (cohorts 1-4h) and part 2 (cohort 5), and a Follow-up Phase up to 52 weeks.
Only the first 6 of 15 groups are shown.
Oral Lead In (OLI) Phase
| Stage | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| STARTED | 138 | 0 | 0 | 0 | 0 | 0 |
| Not Randomized to Injection Phase | 13 | 0 | 0 | 0 | 0 | 0 |
| Randomized to Injection Phase | 125 | 0 | 0 | 0 | 0 | 0 |
| Withdrawn From Study After Randomization and Before Receiving an Injection | 8 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 117 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 21 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 17 | 0 | 0 | 0 | 0 | 0 |
| Physician Decision | 3 | 0 | 0 | 0 | 0 | 0 |
| Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 |
Injection Phase
| Stage | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| STARTED | 0 | 18 | 2 | 9 | 1 | 13 |
| COMPLETED | 0 | 18 | 2 | 9 | 1 | 13 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
Follow-up Phase
| Stage | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| STARTED | 0 | 18 | 2 | 9 | 1 | 13 |
| COMPLETED | 0 | 18 | 1 | 8 | 1 | 12 |
| NOT COMPLETED | 0 | 0 | 1 | 1 | 0 | 1 |
Reasons for not completing this period:
| Reason | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|
| Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: PK population included all participants in the Safety population (all participants who received at least one dose of study treatment (oral or injection)) who received study treatment and had at least 1 non-missing PK assessment (non-quantifiable \[NQ\] values will be considered as non-missing values). Only those participants with data available at specified time points have been analyzed. For Part 1: Cohort 3 (C3) CAB400 \[1\] group, 2 participants received 400 mg instead of 600 mg for Injection 1.
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.
Only the first 6 of 16 groups are shown.
| Characteristic | Unit | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 13 | 18 | 2 | 11 | 1 | 16 | |
| Age, Customized: Adult (18-64 years) | Participants | 13 | 18 | 2 | 11 | 1 | 16 |
| Sex: Female, Male: Female | Participants | 7 | 12 | 1 | 3 | 0 | 6 |
| Sex: Female, Male: Male | Participants | 6 | 6 | 1 | 8 | 1 | 10 |
| Race/Ethnicity, Customized: De-identified | Participants | 11 | 17 | 2 | 11 | 1 | 16 |
| Race/Ethnicity, Customized: Other, unspecified | Participants | 2 | 1 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h, measured over Injection 1 - Day 1 to Week 4.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Hour (h) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is Tmax: the time at which the maximum observed CAB concentration in plasma is reached. It is measured in hours and concerns CAB 400 mg/mL after Injection 1, over the period from Day 1 to Week 4. The registry record says blood samples were collected for pharmacokinetic analysis and that the parameter was determined using standard non-compartmental methods.
Tmax helps characterize the timing of drug exposure after administration. Unlike a measure of how much drug is present, it focuses on when the observed peak occurs. In general, pharmacokinetic measures can describe different aspects of exposure, and a timing measure should not be treated as interchangeable with measures of concentration or total exposure.
The primary endpoint was restricted to participants receiving the CAB 400 mg/mL formulation in Part 1 cohorts 1, 2, 3, 4, 4b, and 4h. It therefore does not directly summarize all formulations, routes, cohorts, or Part 2 regimens in the study. The registry record does not report the group means, standard deviations, or other numerical results for this endpoint. Without those values, the timing of the observed peak cannot be compared quantitatively from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a continuous primary pharmacokinetic endpoint: Tmax after the first CAB 400 mg/mL injection in specified Part 1 cohorts. It also identifies the planned summary as a mean with standard deviation. However, the numerical primary results are not reported in the registry record. There is consequently no posted mean or standard deviation to interpret, and no numerical basis in the record for describing the size or precision of a difference between groups.
The endpoint is a timing measure, not a direct clinical outcome. In general, Tmax indicates when the highest observed plasma concentration occurs during the measurement period. It does not alone describe the concentration at that peak, the total exposure over time, safety, tolerability, or a clinical effect. Other pharmacokinetic outcomes listed in the record include Cmax, AUC(0-t), C24, and Ctau, but their presence among the outcomes does not supply their numerical results.
The design includes multiple cohorts and varied administration routes, sites, doses, and adjunct treatments. Those differences matter when interpreting any comparison: results from one cohort or regimen would not automatically apply to another. The primary endpoint specifically focuses on CAB 400 mg/mL recipients in the named Part 1 cohorts; it does not, by its definition, establish a contrast with every CAB 200 mg/mL group or with the Part 2 schedule.
The record reports 28 outcome measures and 27 analyses, but the numerical primary endpoint findings and the statistical plan are not reported in the registry record. There is no basis in the record to state whether an observed comparison met a prespecified threshold, how uncertainty was quantified, or whether an adjustment for multiple analyses was used. The posted safety counts are descriptive and do not replace the missing pharmacokinetic result.
These limits are important in a Phase 1 study. Such a design can characterize pharmacokinetics and collect safety information in the studied population, but the record alone does not establish the meaning of any unreported estimate. A missing numerical result is not evidence that groups were identical, nor is it evidence of a difference. Interpretation must stop at what the registry record actually reports.
9. Statistical Methods Explained
The primary measure, Tmax, is a continuous pharmacokinetic variable expressed in hours. The registry record specifies a mean and standard deviation as its summary. It also states that CAB pharmacokinetic parameters were determined using standard non-compartmental methods. The record does not provide the detailed calculation conventions, sampling schedule, model specification, or numerical endpoint estimates.
What does Tmax describe?
In general, Tmax is the time associated with the highest observed concentration in the sampled concentration profile. It is tied to the observation schedule: the observed peak is identified from collected samples, rather than from a guarantee that the exact biological peak was captured. The record says blood samples were collected, but does not report their detailed timing. Therefore, the extent to which sampling intervals could affect the observed peak cannot be assessed from the record.
Tmax differs from Cmax, which describes the maximum observed concentration, and from AUC, which describes exposure over a specified period. The registry lists other pharmacokinetic outcomes, including Cmax for oral CAB, Tmax for oral CAB, AUC(0-t), C24, Ctau, and Cmax of CAB 200 for Cohort 4h. These are distinct quantities. A result for one would not substitute for the missing primary Tmax result.
Why report a mean and standard deviation?
In general, the mean describes the central value of a continuous measure, while the standard deviation describes how spread out observations are around that mean. The standard deviation is not itself a confidence interval and does not directly show how precisely the mean is estimated. A confidence interval, when reported, expresses uncertainty around an estimate under specified assumptions. The registry record does not report a confidence interval for the primary endpoint.
Tmax may have a skewed distribution, because a timing measure can cluster at some observed times while extending across other times. In general, a mean and standard deviation can be less informative about a skewed distribution than summaries that also show the shape or median. The record does not report a distributional assessment or a rationale for choosing the stated summary, so it is not possible to judge whether the mean adequately represents each cohort’s observations.
What do non-compartmental methods mean?
In general, non-compartmental pharmacokinetic methods summarize observed concentration-time data without requiring the investigator to specify a compartment model for the body. Different pharmacokinetic measures are derived from the observed profile. The registry record names the method family but does not report the exact derivation rules, handling of values below quantification limits, or software and analysis settings. It states that non-quantifiable values were considered non-missing for the population definition; that statement does not explain how such values were used in each endpoint calculation.
How should planning illustrations be read?
Any sample-size calculations associated with observed effects are planning illustrations rather than observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such illustrations answer a hypothetical design question under those assumptions. They do not show the power of the completed trial, and they cannot recover a missing primary result. The record does not report a trial-specific sample-size justification, so the planning assumptions should not be mistaken for the study’s original design rationale.
In general, variability and precision depend on the number of observations and their distribution, in addition to the mean and standard deviation. No new estimate should be derived without the underlying results and a defined comparison. Because the primary numerical summary is not reported in the registry record, the endpoint’s magnitude, spread, and uncertainty cannot be assessed from that record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 28 outcome measures and 27 analyses. It identifies several pharmacokinetic outcomes and safety outcomes across Part 1 and Part 2. When a study examines many outcomes or comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control the interpretation of multiple statistical tests, but the appropriate method depends on the prespecified questions and analysis plan.
The multiplicity strategy is not reported in the registry record. The record also does not report whether outcomes were arranged in a formal testing hierarchy, whether analyses were adjusted for multiple comparisons, or whether any interim analyses were planned or conducted. No conclusion about such procedures can be drawn from the count of outcomes and analyses alone.
The registry record describes the pharmacokinetic population as participants in the Safety population who received study treatment and had at least one non-missing pharmacokinetic assessment; non-quantifiable values were considered non-missing for that definition. This definition does not state how many participants contributed to the primary endpoint, nor does it fully describe endpoint-specific missing-data handling. The number of missing assessments, reasons for missingness, and any imputation procedure are not reported in the registry record.
The general distinction between a safety population and a pharmacokinetic population matters: the latter depends on the availability of pharmacokinetic assessments as well as treatment receipt. Results from those populations need not have the same denominators. The registry record does not provide the primary endpoint denominators or the detailed population flow needed to assess how exclusions or missing assessments might affect the estimate.
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 |
|---|---|---|---|
| Oral Cabotegravir (CAB) 30 | 0 | 13 | 0.0% |
| Part 1: Cohort 1 (C1) CAB400 | 0 | 18 | 0.0% |
| Part 1: Cohort 1 (C1) CAB200 | 0 | 2 | 0.0% |
| Part 1: Cohort 2 (C2) CAB400 | 0 | 11 | 0.0% |
| Part 1: Cohort 2 (C2) CAB200 | 0 | 1 | 0.0% |
| Part 1: Cohort 3 (C3) CAB400 | 2 | 16 | 12.5% |
| Part 1: Cohort 3 (C3) CAB200 | 0 | 2 | 0.0% |
| Part 1: Cohort 4 (C4) CAB400 | 0 | 18 | 0.0% |
| Part 1: Cohort 4 (C4) CAB200 | 0 | 2 | 0.0% |
| Part 1: Cohort 4b Group 1 (C4b G1) | 0 | 13 | 0.0% |
| Part 1: Cohort 4b Group 2 (C4b G2) | 1 | 14 | 7.1% |
| Part 1: Cohort 4h (C4h) CAB400 + rHuPH20 | 0 | 9 | 0.0% |
| Part 1: Cohort 4h (C4h) CAB200 + rHuPH20 | 0 | 8 | 0.0% |
| Part 2: Cohort 5 (C5) CAB400 | 0 | 10 | 0.0% |
| Part 2: Cohort 5 (C5) CAB200 | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Oral Cabotegravir (CAB) 30 | 0 of 13 |
| Part 1: Cohort 1 (C1) CAB400 | 0 of 18 |
| Part 1: Cohort 1 (C1) CAB200 | 0 of 2 |
| Part 1: Cohort 2 (C2) CAB400 | 0 of 11 |
| Part 1: Cohort 2 (C2) CAB200 | 0 of 1 |
| Part 1: Cohort 3 (C3) CAB400 | 0 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Oral Cabotegravir (CAB) 30 | 4 of 13 |
| Part 1: Cohort 1 (C1) CAB400 | 18 of 18 |
| Part 1: Cohort 1 (C1) CAB200 | 2 of 2 |
| Part 1: Cohort 2 (C2) CAB400 | 10 of 11 |
| Part 1: Cohort 2 (C2) CAB200 | 1 of 1 |
| Part 1: Cohort 3 (C3) CAB400 | 15 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|---|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 0 of 13 | 0 of 18 | 0 of 2 | 0 of 11 | 0 of 1 | 1 of 16 |
| Anxiety | Psychiatric disorders | 0 of 13 | 0 of 18 | 0 of 2 | 0 of 11 | 0 of 1 | 1 of 16 |
| Hiatus hernia | Gastrointestinal disorders | 0 of 13 | 0 of 18 | 0 of 2 | 0 of 11 | 0 of 1 | 0 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Oral Cabotegravir (CAB) 30 | Part 1: Cohort 1 (C1) CAB400 | Part 1: Cohort 1 (C1) CAB200 | Part 1: Cohort 2 (C2) CAB400 | Part 1: Cohort 2 (C2) CAB200 | Part 1: Cohort 3 (C3) CAB400 |
|---|---|---|---|---|---|---|---|
| Injection site pain | General disorders | 0 of 13 | 18 of 18 | 2 of 2 | 8 of 11 | 1 of 1 | 12 of 16 |
| Injection site erythema | General disorders | 0 of 13 | 8 of 18 | 1 of 2 | 8 of 11 | 0 of 1 | 4 of 16 |
| Injection site nodule | General disorders | 0 of 13 | 10 of 18 | 0 of 2 | 4 of 11 | 1 of 1 | 1 of 16 |
| Injection site induration | General disorders | 0 of 13 | 6 of 18 | 0 of 2 | 5 of 11 | 0 of 1 | 3 of 16 |
| Headache | Nervous system disorders | 1 of 13 | 2 of 18 | 0 of 2 | 3 of 11 | 0 of 1 | 6 of 16 |
| Injection site swelling | General disorders | 0 of 13 | 2 of 18 | 0 of 2 | 4 of 11 | 0 of 1 | 6 of 16 |
| Injection site warmth | General disorders | 0 of 13 | 5 of 18 | 0 of 2 | 2 of 11 | 0 of 1 | 3 of 16 |
| Injection site pruritus | General disorders | 0 of 13 | 1 of 18 | 0 of 2 | 5 of 11 | 0 of 1 | 4 of 16 |
| Blood creatine phosphokinase increased | Investigations | 0 of 13 | 3 of 18 | 1 of 2 | 0 of 11 | 0 of 1 | 1 of 16 |
| Nausea | Gastrointestinal disorders | 0 of 13 | 1 of 18 | 0 of 2 | 1 of 11 | 0 of 1 | 3 of 16 |
Serious events with the highest arm-level rate: hiatus hernia (7.1%), abortion spontaneous (6.2%), anxiety (6.2%).
The registry record gives group-level counts for participants with serious adverse events, participants with other adverse events, and deaths. In the CAB 400 mg/mL group for Cohort 3, the serious adverse event count is 2; in Cohort 4b Group 2, it is 1. The serious adverse event count is 0 in each of the other listed groups. The death count is 0 in every listed group. These are descriptive counts for the groups as recorded and should not be read as comparisons adjusted for differences between cohorts.
Other adverse events were recorded in each listed group, with counts varying by group. Those counts do not mean the same thing as serious adverse events, and the two categories should not be conflated. The registry record also lists Hiatus hernia at 7.1%, Abortion spontaneous at 6.2%, and Anxiety at 6.2% among the top serious terms. The record does not give enough context with those percentages to establish their denominators or assign them to a particular cohort.
In general, a count is not a rate unless its denominator and observation period are clear. Cohort size, treatment exposure, and follow-up can affect interpretation. These safety summaries do not establish causation, comparative risk, or safety beyond the studied participants and regimens.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized Phase 1 investigation of cabotegravir pharmacokinetics, safety, and tolerability in healthy adults. Its primary endpoint asks when the maximum observed plasma concentration occurred after the first CAB 400 mg/mL injection in specified Part 1 cohorts. This is a pharmacokinetic characterization question, not a direct test of clinical benefit.
The record does not report the numerical primary endpoint result. It therefore cannot show from the posted information whether mean Tmax differed between groups, how large any difference was, or how precisely it was estimated. The absence of a numerical result does not establish either similarity or difference. It also does not justify an inference about the results of other pharmacokinetic outcomes.
The registry reports safety counts, including serious adverse events and deaths. Those counts describe events recorded for the listed groups, but they do not establish that a treatment caused or prevented an event. Nor do they provide a complete comparison of risk without clear denominators, exposure, follow-up, and an appropriate analysis. The listed serious-event terms also require context that is not reported in the registry record.
In general, conclusions from an early-phase study in healthy adults are specific to the participants, doses, formulations, administration routes, and follow-up examined. They should not be treated as evidence about clinical outcomes in people with HIV or about regimens not evaluated in the stated cohorts. The registry record does not report enough information to make broader efficacy or comparative safety claims.
The responsible interpretation is therefore bounded: the study design and endpoint are described, and some safety counts are posted, but the central numerical pharmacokinetic result is not reported in the registry record. Any conclusion about the size, direction, or precision of the primary endpoint would require information not present in that record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a focused pharmacokinetic endpoint with a study structure that varies formulation, dose, injection route, injection site, and adjunct treatments. Those design differences create distinct questions rather than a single universal CAB comparison. The primary Tmax endpoint is specifically defined for CAB 400 mg/mL in selected Part 1 cohorts, which limits the scope of any interpretation to that endpoint and those groups.
The study also illustrates why an endpoint definition and an outcome result are separate pieces of evidence. The record explains what was measured, the timeframe, and the summary method, but does not report the numerical primary result. A well-described endpoint cannot substitute for its estimate, variability, or uncertainty. Likewise, the presence of safety counts does not fill the gap in pharmacokinetic reporting.
In general, early pharmacokinetic research can help characterize exposure and guide questions for subsequent research. Interpretation depends on the sampling schedule, analysis population, variability, and the comparisons specified in the analysis plan. The record does not report several of these details, including the complete analysis plan and endpoint-specific missingness information.
The statistical lesson is to separate what a registry record establishes from what it leaves unresolved. Here, the design and intended measurement are clear enough to describe, while the main numerical estimate and its precision are not available in the record. That distinction prevents an unreported result from being mistaken for evidence of no difference or for a positive finding.
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 its numerical results are not reported in the registry record. The mean, standard deviation, group denominators, and uncertainty estimates are unavailable there. This prevents quantitative assessment of the endpoint’s distribution or comparison across cohorts.
The record describes standard non-compartmental methods but does not provide the detailed sampling schedule, endpoint calculation rules, or analysis settings. Since Tmax is based on observed concentrations over time, missing sampling details limit assessment of how well the observed peak reflects the concentration-time profile. The record’s population description addresses non-missing pharmacokinetic assessments, but endpoint-level missingness and its handling are not reported.
Several regimens differ in dose, formulation, route, injection site, schedule, or accompanying topical and hyaluronidase treatments. Those variations mean that groups should not be treated as interchangeable. The record does not provide enough detail to identify a single comparison that represents every study question, and some arm descriptions are incomplete.
The registry record does not report a detailed multiplicity plan, trial-specific sample-size justification, interim analysis information, or complete statistical analysis plan. It also does not provide denominators and context for the listed serious-event percentages. These gaps constrain interpretation of both pharmacokinetic and safety findings. Finally, the study population is described as healthy adults, so the record does not establish how findings would apply to other populations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants — NCT04484337.
- Registry record last updated 2026-05-29; status last verified 2026-02.
- Results first posted 2026-05-29.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT04484337 is a completed, randomized, double-blind, active-control Phase 1 study of repeat-dose cabotegravir formulations in healthy adult participants. The registry record gives enrollment as 138, a study start of 2020-07-31, and primary completion on 2023-05-05. The two-part study included an oral CAB lead-in, multiple Part 1 injection regimens, and a Part 2 cohort with intramuscular gluteal injections approximately 12 weeks apart.
The primary endpoint was Tmax after the first CAB 400 mg/mL injection in specified Part 1 cohorts, summarized as a mean and standard deviation. The registry record does not report its numerical results. It lists 28 outcome measures and 27 analyses and includes group-level adverse event counts. The statistical plan, multiplicity handling, detailed endpoint missingness, and some analysis details are not reported in the registry record.