Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children (NCT01854775), a non-randomized phase 2, phase 3 study. The primary outcome is Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1).

2. Clinical Question

In practical terms, the registry describes a study of how the regimen was assessed in adolescents and children with different treatment histories and body-weight ranges. Cohort 1 was treatment-naive, while Cohorts 2 and 3 were virologically suppressed. The planned regimen and the primary pharmacokinetic endpoint therefore need to be understood in the context of each cohort rather than treated as a single homogeneous comparison.

The primary endpoint does not compare the regimen against another treatment. It is a continuous pharmacokinetic measure, reported in the registry as a mean, and its stated analysis population is a pharmacokinetic substudy set. Safety and antiviral activity are also part of the study objectives, but the registry record does not report an observed primary endpoint result or a randomized treatment contrast.

3. Trial Design

This was a Phase 2/3, open-label, nonrandomized, parallel study sponsored by Gilead Sciences. The registry lists the study as completed, with enrollment of 129. The study started on 2013-05-06 and its primary completion date was 2020-05-11. It involved three cohorts defined by age, weight, and treatment status rather than by random assignment to comparable arms.

Cohort 1 comprised treatment-naive adolescents aged 12 to < 18 years and weighing ≥ 35 kg. The listed treatment was E/C/F/TAF 150/150/200/10 mg once daily for 48 weeks. Cohort 2 comprised virologically suppressed children aged 6 to < 12 years and weighing ≥ 25 kg, receiving the same listed strength once daily for 48 weeks. Cohort 3 comprised virologically suppressed children aged ≥ 2 years and weighing ≥ 14 to < 25 kg, receiving the low-dose 90/90/120/6 mg regimen for 48 weeks. The registry says Cohort 3 participants who attained a weight of ≥ 25 kg would switch to the 150/150/200/10 mg tablets.

The study objectives varied by cohort. For Cohort 1, the stated primary objectives included evaluating steady-state pharmacokinetics for elvitegravir and tenofovir alafenamide and confirming the dose, as well as evaluating safety and tolerability through Week 24. Cohort 2 objectives included evaluating pharmacokinetics and safety and tolerability through Week 24. Cohort 3 objectives included pharmacokinetics, dose confirmation, and safety and tolerability of the low-dose regimen.

Because allocation was nonrandomized and the study had no masking, comparisons across cohorts are descriptive rather than randomized treatment comparisons. Cohorts also differ in baseline treatment status, age and weight criteria, and—in Cohort 3—the listed dose. A sample-size justification, detailed randomization procedure, or further statistical design rationale is 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: 155 participants were screened.

Treatment Phase (48 Weeks)

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The PK Substudy Analysis Set included all enrolled and treated participants from Part A who had any nonmissing key PK parameters (AUCtau, AUClast, Cmax) from Week 4 intensive PK data for the respective analyte.

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: The Safety Analysis Set included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1), measured over 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4.

The primary endpoint listed in the registry is the pharmacokinetic parameter AUCtau for elvitegravir in Cohort 1. AUCtau is defined as the area under the concentration-versus-time curve over the dosing interval, and the unit is hr*ng/mL. The registry specifies measurement at Week 4, with blood sampling at pre-dose, 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose. The endpoint is summarized as a mean with standard deviation.

General statistical context: An area under the concentration-time curve condenses a series of measured drug concentrations across a dosing interval into an exposure measure. It is used in pharmacokinetic assessment because exposure over time can inform evaluation of a regimen and dose. A mean describes the central value of the observed measurements, while the standard deviation describes variation among measurements around that mean. These summaries do not by themselves establish a treatment effect or compare the regimen with an alternative.

The specified analysis population was the pharmacokinetic substudy analysis set: enrolled and treated participants from Part A with any nonmissing key pharmacokinetic parameters from the Week 4 intensive pharmacokinetic data for the relevant analyte. The registry record does not report the observed mean, standard deviation, or number analyzed for this endpoint, so its magnitude and precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is more complete about endpoint definitions and populations than about analysis results. It identifies a continuous primary pharmacokinetic endpoint, describes the summary measure as a mean with standard deviation, and defines the pharmacokinetic analysis set. It does not report an estimate for the primary endpoint, a confidence interval, a hypothesis test, or the number of participants included in that endpoint analysis.

What does the primary measure represent?

AUCtau is the area under the concentration-versus-time curve over the dosing interval. In this study, the listed analyte is elvitegravir, the unit is hr*ng/mL, and measurement was specified at Week 4. The sampling schedule spans pre-dose and post-dose time points through 24 hours. General statistical context: The area-under-the-curve approach summarizes repeated concentration measurements over time into an exposure measure. It differs from a single concentration measurement because it reflects the curve across the dosing interval. The registry does not provide the observed concentration curve or the resulting AUCtau estimate.

Why report a mean and standard deviation?

The endpoint is continuous, and the registry specifies a mean as its summary parameter and standard deviation as its measure of dispersion. The mean represents the average observed value in the analysis set. The standard deviation describes how spread out individual measurements are around that average. General statistical context: A standard deviation is not the same as the standard error or a confidence interval. The standard deviation describes variability among observations; a confidence interval describes uncertainty around an estimated quantity under a statistical method. Neither the endpoint's mean nor its standard deviation is reported in the registry record, and no confidence interval is listed.

Who was included in the endpoint analysis?

The pharmacokinetic substudy analysis set included enrolled and treated participants from Part A who had any nonmissing key pharmacokinetic parameters—AUCtau, AUClast, or Cmax—from Week 4 intensive pharmacokinetic data for the respective analyte. This definition is narrower than simply counting all enrolled participants. Overall enrollment was 129, but the number included in the primary endpoint analysis is not reported in the registry record. The handling of participants with incomplete measurements beyond this inclusion definition is also not reported.

What does the design allow the reader to compare?

The registry classifies the study as nonrandomized, open-label, and parallel. It describes separate cohorts with different eligibility criteria and treatment histories. Cohort 1 was treatment-naive, whereas Cohorts 2 and 3 were virologically suppressed; age and weight criteria also differed, and Cohort 3 received a low-dose regimen. These design features mean that cross-cohort contrasts are not equivalent to randomized comparisons. The registry specifically warns that the arms are not a like-for-like control comparison. No control group or masking procedure is listed.

General statistical context: Random allocation is one way to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. Without randomization, differences between groups may reflect their distinct participant characteristics as well as any treatment-related factors. In this study, cohort membership itself is tied to age, weight, and treatment status, so descriptive cohort differences should not be interpreted as isolated treatment effects.

What can be said about testing and multiplicity?

The registry lists 66 outcome measures and no analyses. It does not report a hypothesis test or a multiplicity adjustment for the primary endpoint, nor does it describe an analysis plan covering the many listed outcomes. General statistical context: When many outcomes or comparisons are examined, the chance of finding at least one apparently unusual result by chance can increase. Prespecified testing strategies or adjustment methods can address aspects of this issue, but the applicable approach cannot be determined from the registry record. A named primary endpoint does not, by itself, reveal how multiplicity was handled.

How should planning calculations be read?

The stated sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the stated quantity is total events using the Schoenfeld method; other illustrations are participants per arm. These are planning illustrations, not observed power. They do not establish the trial's original sample-size rationale, which is not reported in the registry record. Because the study is nonrandomized and its cohorts are not like-for-like controls, a hypothetical equal-allocation calculation should not be mistaken for the actual cohort structure.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg")
n   <- c(24)
m   <- c(23840.1)
sp  <- c(6076.15)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg  24  23840.100  6076.150  21274.367  26405.833

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 66 outcome measures but no analyses. It names a primary pharmacokinetic endpoint and describes additional pharmacokinetic outcomes, as well as safety and antiviral activity objectives. A multiplicity strategy—such as a hierarchy of tests, an adjustment method, or a distinction between confirmatory and exploratory outcomes—is not reported in the registry record. As a result, the record does not establish how any family of statistical tests was controlled or interpreted.

The primary endpoint analysis population is defined as enrolled and treated participants from Part A with any nonmissing key pharmacokinetic parameters from Week 4 intensive data for the respective analyte. This is a stated population rule, not a report of how many participants contributed to the endpoint. The number analyzed, the amount and pattern of missing data, and the reasons for missing measurements are not reported in the registry record.

Imputation, sensitivity analyses, and other methods for addressing missing measurements are not reported in the registry record. The definition of the analysis set indicates that participants without any nonmissing key parameters would not meet its stated inclusion criterion, but it does not explain how partially observed pharmacokinetic data were handled in the endpoint calculation.

General statistical context: Missing data can affect both the number of observations available and the interpretation of an estimate, particularly if missingness is related to participant characteristics or measured outcomes. The available registry description does not permit an assessment of those patterns or their impact.

The registry also does not report the statistical analysis plan, any interim analyses, or a sample-size justification. The stated planning assumptions are illustrations and should not be taken as documentation of the study's original analysis decisions.

12. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: suicide attempt (4.0%), pneumonia (3.7%), uveitis (2.0%), visual impairment (2.0%), constipation (2.0%).

The registry reports serious adverse event counts by cohort and separate counts for participants affected by other adverse events. Cohort 1 lists 50 at risk, 10 affected by serious adverse events, 47 affected by other adverse events, and 1 death. Cohort 2 lists 52 at risk, 7 affected by serious adverse events, 45 affected by other adverse events, and 0 deaths. Cohort 3 lists 27 at risk, 1 affected by serious adverse events, 25 affected by other adverse events, and 0 deaths.

These are descriptive counts within cohorts with different eligibility criteria, treatment histories, and regimen details. They are not a randomized comparison, and the counts alone do not show whether an event was caused by study treatment. The registry lists the serious adverse event terms Suicide attempt at 4.0%, Pneumonia at 3.7%, and Uveitis, Visual impairment, Constipation, and Abscess limb at 2.0% each. The denominator and cohort distribution for these term-specific percentages are not reported in the registry record.

General statistical context: Event counts describe how many participants were recorded as affected, while a comparison of risk would require a clearly specified contrast and suitable analysis. The registry record does not provide such a randomized contrast. The listed deaths are reported as counts; causes and attribution are not reported in the registry record.

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

The registry record establishes what the study set out to assess: pharmacokinetics, dose confirmation, safety and tolerability, and antiviral activity in adolescent and child cohorts with HIV-1 infection. It specifies a Week 4 elvitegravir AUCtau endpoint for Cohort 1 and defines the pharmacokinetic analysis population. It also provides cohort-level safety counts and lists selected serious adverse event terms and percentages.

These descriptions do not reveal the observed primary endpoint value. The registry record does not report the primary mean, its standard deviation, a confidence interval, or a statistical test result. Thus, the endpoint's magnitude and precision cannot be evaluated from the information reported. Nor does a study objective by itself demonstrate a result for pharmacokinetics, antiviral activity, or safety.

The study is nonrandomized and open-label, and its cohorts differ in age, weight, treatment history, and regimen. The registry notes that the arms are not a like-for-like control comparison. Therefore, the posted cohort counts should be read as descriptive rather than as estimates of a randomized treatment effect. The safety counts do not establish that the regimen caused the recorded events, and they do not provide a controlled basis for attributing differences between cohorts.

General statistical context: A result is more informative when its estimate is paired with a measure of uncertainty and interpreted in light of the design and analysis population. Here, the registry record does not report the primary estimate or its uncertainty, and the analyzed sample size is not stated. Overall enrollment of 129 cannot be substituted for the number with usable Week 4 pharmacokinetic data.

The record also does not report the trial's sample-size justification, multiplicity approach, missing-data methods, or full statistical analysis plan. The planning assumptions described for sample-size illustrations are not a report of observed power or of the study's original design rationale. Conclusions should therefore be limited to the stated design, endpoint definition, analysis-set criteria, and descriptive safety counts.

14. Why This Trial Matters Statistically

Statistically, this study is notable for combining pharmacokinetic assessment and safety objectives across pediatric cohorts with different age and weight ranges and different treatment histories. The registry identifies a specific continuous exposure measure—elvitegravir AUCtau at Week 4 in Cohort 1—while also describing pharmacokinetic and safety objectives for Cohorts 2 and 3. Keeping those cohorts distinct is essential to interpreting the study because their eligibility criteria and treatment circumstances differ.

The record also illustrates the difference between a clearly defined endpoint and a fully reported result. It specifies the measurement interval, unit, summary parameter, and analysis-set criteria, but the observed endpoint estimate and its uncertainty are not reported in the registry record. Without those results, readers cannot assess the value or precision of the primary measure from this record.

The nonrandomized, open-label design matters to statistical interpretation. Cohorts were not assigned randomly to comparable treatments, and the registry cautions that the arms are not a like-for-like control comparison. This makes descriptive reporting of cohort-specific outcomes more appropriate than interpreting between-cohort differences as treatment effects.

Finally, the registry lists many outcomes while reporting no analyses and no multiplicity strategy. That makes it important to distinguish the stated objectives from any inferential conclusions and to look for a complete analysis report before drawing conclusions about outcome estimates. The record's safety counts are useful as descriptions of what was recorded by cohort, but not as evidence of causality or comparative risk.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint result is not reported in the registry record. The record also does not provide its standard deviation, confidence interval, test result, or analyzed sample size, preventing assessment of the endpoint's observed magnitude and precision. Although overall enrollment was 129, the endpoint population has additional inclusion criteria, so overall enrollment does not identify how many participants contributed to the Week 4 pharmacokinetic analysis.

The design is nonrandomized and open-label. Cohorts differ by age, weight, treatment history, and, for Cohort 3, listed dose. Consequently, the cohorts cannot be treated as interchangeable comparison groups. The registry explicitly says that the arms are not a like-for-like control comparison.

The registry lists 66 outcome measures but no analyses. It does not report a statistical analysis plan, multiplicity handling, missing-data methods, or interim analyses. The number of missing endpoint observations and their reasons are also not reported in the registry record. These omissions limit assessment of selection into the analysis set and of the robustness of any endpoint estimate.

Safety reporting is descriptive: the registry gives affected counts and deaths by cohort and selected serious adverse event terms with percentages. It does not report the denominator or cohort distribution for those term-specific percentages, nor does it provide information attributing events to treatment. The counts therefore do not support causal interpretation or a randomized safety comparison.

The registry does not report the trial's sample-size justification. Planning illustrations based on an observed effect and stated assumptions are not a substitute for that justification and are not observed power. The record also describes study objectives but does not include observed results for the listed primary pharmacokinetic endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children — NCT01854775.
• Registry record last updated 2026-01-09; status last verified 2025-12.
• Results first posted 2021-05-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase 2/3 study was nonrandomized, open-label, and parallel, with overall enrollment of 129. It evaluated E/C/F/TAF in three HIV-1 cohorts: treatment-naive adolescents aged 12 to < 18 years and weighing ≥ 35 kg, virologically suppressed children aged 6 to < 12 years and weighing ≥ 25 kg, and virologically suppressed children aged ≥ 2 years and weighing ≥ 14 to < 25 kg. The listed Cohort 3 regimen was low dose, with a switch to the higher listed regimen if a participant attained a weight of ≥ 25 kg.

The primary endpoint listed is mean elvitegravir AUCtau in Cohort 1 at Week 4, measured in hr*ng/mL. The analysis set requires enrolled and treated Part A participants with nonmissing key Week 4 pharmacokinetic parameters for the respective analyte. The observed endpoint estimate, uncertainty, and analyzed sample size are not reported in the registry record. Cohort-level adverse event counts are listed, but the nonrandomized design does not provide a like-for-like control comparison.