Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers (NCT03894124), a na phase 1 study. The primary outcome is Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose..

2. Clinical Question

3. Trial Design

The registry classifies this as a phase 1, single-group study with no masking. Allocation is recorded as NA, and there is no like-for-like control group. The listed enrollment is 24. The study was marked completed; its recorded start date is 2019-06-12 and its primary completion date is 2019-07-25.

Participants received Pifeltro® (doravirine 100mg) daily for 7 days. The objective was to examine plasma doravirine pharmacokinetics after daily intake stopped. The primary outcome covers concentrations from before the last dose through 72 hours after dosing. The registry describes blood collection before the dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 hours post-dose. These are repeated observations within a single-group study, not observations from a randomized comparison.

The record identifies healthy volunteers as the study population. Human Immunodeficiency Virus is listed among the conditions, but the summary does not describe participants as having that condition. The registry lists a secondary outcome concerning participants with treatment-emergent adverse events. It records five outcome measures overall, but numerical results for the pharmacokinetic outcome are not reported in the registry record. The detailed statistical analysis plan, sample-size justification and handling of repeated measurements 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Plasma concentrations of doravirine after drug intake cessation up to 72 hours post-dose were investigated in population of participants for the study

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: Fourteen (14) participants completed are considered sufficient to allow for relevant conclusions to be drawn, given experience from similar studies conducted previously.

6. Primary Endpoint

The registry lists the primary outcome as Steady State Plasma Concentrations of Doravirine After Drug Intake Cessation up to 72 Hours Post-dose., measured over 72 hours from treatment cessation; days 7-10 inclusive from enrolment.

The primary outcome is titled as steady-state plasma concentrations of doravirine after drug intake cessation, through 72 hours post-dose. It is intended to describe how measured plasma drug concentrations change over time after the last daily dose. The registry specifies a geometric mean with a 95% confidence interval and gives the unit as ng*hr/mL. That unit is reproduced as registered; the record does not explain its relationship to the concentration measurements.

Pharmacokinetic measurements over time can characterize drug exposure and the pattern of decline after dosing stops. In general, a geometric mean is useful when measurements are positive and their distribution is better described on a multiplicative scale than on an additive scale. A confidence interval conveys uncertainty around an estimated quantity; it is not a range that is guaranteed to contain every participant’s measurement.

The record describes a pre-dose sample and samples at the listed post-dose times through 72 hours. It does not report the geometric-mean estimates, confidence-interval limits, participant-level measurements or results at individual timepoints. Therefore, the outcome definition and sampling schedule can be described, but the observed concentration pattern and its precision cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group study, with allocation recorded as NA and masking listed as none. In general, a single-group design can describe measurements made in participants receiving the study intervention, but it cannot separate changes associated with time or study procedures from differences that might have appeared under a distinct comparator condition. This record does not include a randomized control group or a between-group treatment contrast.

What does the primary outcome measure?

The primary outcome concerns plasma doravirine concentrations after daily intake ceased. The registry specifies a geometric mean and a 95% confidence interval. In general, the geometric mean summarizes values on a multiplicative scale and can be appropriate for positive measurements with a skewed distribution. It is not the same as the arithmetic average. The registry does not report the calculation details, any transformation used, or whether the estimates were calculated separately for each timepoint.

A confidence interval expresses uncertainty in an estimated quantity under the statistical method used. In general, a narrower interval indicates greater precision than a wider interval, while the interval’s interpretation depends on the assumptions of that method. Since no estimate or interval limits are reported for the primary outcome, its precision cannot be assessed from the record. The outcome’s listed unit is ng*hr/mL; the registry does not explain that unit further.

Why are the repeated measurements relevant?

Samples were planned before the last dose and at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 hours post-dose. Measurements from the same participant are generally related rather than independent. In general, analysis of repeated measurements should account for that within-person relationship if a model combines observations across time. The registry does not report whether a repeated-measures model was used, how within-person dependence was handled, or whether results were estimated separately at each scheduled time.

The record describes the primary outcome as covering the period through 72 hours, but a sampling schedule alone does not reveal the observed concentration curve. To interpret a time course, readers need the numerical estimates and a clear account of the analysis used to produce them. Neither is reported in the registry record.

What can be inferred from the design?

The study was not designed as a like-for-like control comparison in the information recorded. In general, a within-group pattern can describe the measurements made after dosing stops, but it cannot establish how those measurements would differ under another dose, schedule or condition. The record does not describe a model-based causal comparison, and no such comparison should be inferred from the listed outcome.

Enrollment is recorded as 24. A sample-size justification, target precision, or rationale for choosing that enrollment is not reported in the registry record. The registry record also does not report an interim analysis plan or a detailed statistical analysis plan. Without those details, it is not possible to assess how enrollment was linked to precision or whether any planned monitoring or analysis decisions affected reporting.

What is and is not reported about analysis?

The record lists five outcome measures and zero analysis entries. It identifies the primary outcome’s summary measure and confidence level, but does not report numerical results, model specifications, estimation methods or diagnostic checks. In general, a statistical method should match the form of the data and the question being asked; the registry record does not provide enough detail to evaluate that match for this study.

Over-dispersion is a general issue when observed variability exceeds what a chosen model assumes. It can make uncertainty estimates too small if the model does not account for the extra variability. The registry record does not indicate whether over-dispersion was assessed or relevant to the analysis, so it cannot be claimed as a feature of this study. Similarly, the record does not identify any covariate adjustment or sensitivity analysis.

The reported geometric-mean summary and confidence interval are analysis specifications, not outcome results. They do not indicate the direction or size of any concentration change, and they do not establish the precision of an estimate without the actual values. Interpretation is consequently limited to the stated study question, sampling schedule, design and outcome definition.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, identifies a primary pharmacokinetic outcome and names treatment-emergent adverse events as a secondary outcome. It does not report a multiplicity strategy or explain whether any outcomes were considered exploratory. In general, when multiple outcomes or timepoints are tested, the chance of at least one apparently unusual finding can increase; methods such as prespecifying a primary comparison or adjusting for multiple testing can address particular multiplicity concerns. No method should be attributed to this study without documentation.

The primary outcome includes repeated planned measurements through 72 hours. The record does not state whether each timepoint was analyzed as a separate outcome, whether a single overall model was used, or whether adjustments across timepoints were planned. Since numerical analyses are not reported, it is not possible to assess how multiplicity was handled in the posted results.

Missing-data methods and the number of participants contributing to the primary outcome are not reported in the registry record. The record does not say whether all planned samples were available, how an omitted or unusable sample was handled, or whether any participants were excluded from an analysis. The analysis population is also not defined. Enrollment is recorded as 24, while the safety entry lists 14 participants at risk; the record does not explain the difference, and those counts should not be assumed to describe the same analysis population.

The record gives no detailed statistical analysis plan, interim analysis information or sensitivity analyses. These omissions limit assessment of prespecification, missingness and robustness. They do not establish that a particular method was or was not used outside the information recorded in the registry.

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 safety entry lists 14 participants at risk in the study-intervention group. It records zero participants with serious adverse events, six with other adverse events, and zero deaths. No serious adverse-event terms are listed. These counts are descriptive entries in the registry, not estimates of comparative risk.

The safety at-risk count is not the same as the listed enrollment of 24. The registry record does not explain why these figures differ, identify the safety population definition, or state whether the same participants contributed to all safety categories. The six participants in the other adverse-event category should not be assumed to have had serious events: the serious-event count is separately recorded as zero. The record does not give event names, severity details or participant-level descriptions for the other category.

The presence of zero recorded serious events is a report of what the registry lists for this group. It does not establish that an event could not occur, and without a comparator it does not support a relative safety comparison. The record does not report a statistical analysis of adverse events or further details about collection and classification. These limits are important when interpreting the safety counts.

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

The study’s stated purpose is to characterize plasma doravirine concentrations after daily intake ceased, in healthy volunteers who received doravirine daily for 7 days. Its planned observations extend from before the last dose to 72 hours post-dose. This is a pharmacokinetic question about measured concentrations over time, not a comparison of clinical outcomes between treatment groups.

The registry record does not report numerical primary-outcome results. It therefore does not show the geometric means, confidence intervals or timepoint-specific measurements needed to describe how concentrations changed or how precisely they were estimated. The schedule and summary measure identify what the investigators intended to measure, but they do not substitute for the observed results.

The single-group design also limits what can be learned comparatively. There is no separate control group in the registry description, so the record cannot establish how a different dose, dosing schedule or alternative condition would compare. No conclusion about clinical benefit or lack of benefit follows from the concentration outcome definition alone.

In general, pharmacokinetic measurements can inform understanding of drug exposure, but interpretation depends on the actual estimates, their uncertainty, the analysis methods and the population studied. Here, the record identifies healthy volunteers and does not report enough information to assess individual variability, missing samples, or the analysis population. The results should not be generalized beyond the population and measurements described without additional evidence.

The safety entry records zero serious adverse events and zero deaths among 14 participants at risk, alongside six participants with other adverse events. These are registry counts with no separate comparator. The record does not provide enough detail to characterize the other events or explain the safety denominator. Thus, the most supportable reading is that the registry describes a completed single-group pharmacokinetic study and its planned measurements, while leaving the numerical concentration findings and several interpretive details unreported.

13. Why This Trial Matters Statistically

This study illustrates a statistical distinction between defining a measurement and reporting its result. The registry specifies a geometric mean, a 95% confidence interval and a sampling schedule extending through 72 hours after dosing stopped. Those details identify the intended summary and observation period, but without estimates and interval limits, readers cannot assess either the observed pattern or its precision.

The single-group structure is also important. Repeated measurements in the same participants can describe a concentration time course, but they are not an independent control comparison. A statistical interpretation should reflect that design and should not present the within-group observations as evidence of a difference from an unobserved comparator.

The record further shows why enrollment, outcome analysis and safety denominators need to be distinguished. Enrollment is listed as 24, while the safety entry lists 14 participants at risk. The registry does not explain the difference, and it does not define the population contributing to the primary outcome. Without those details, the denominators cannot be reconciled or assumed to apply to every analysis.

More broadly, a clear statistical record needs both an outcome definition and enough analysis information to evaluate how results were produced. Here, the record names five outcome measures but does not report numerical pharmacokinetic findings or a detailed statistical plan. This limits assessment of uncertainty, multiplicity, missing data and repeated-measure modeling. The study remains informative about the intended design and measurement schedule, while its statistical conclusions cannot be evaluated from the registry information alone.

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 interpretation is that numerical primary-outcome results are not reported in the registry record. Without geometric means, confidence intervals or timepoint-level values, the concentration profile and its precision cannot be described. The listed unit is ng*hr/mL, and the record does not explain the unit further.

The study is single-group and has no separate control condition. As a result, it does not provide a between-group comparison. The record also does not report a detailed statistical analysis plan, the method used to account for repeated measurements, or whether estimates were produced at each timepoint or across the full period.

The record does not report missing-sample handling, the number contributing to the primary outcome, the analysis population, or reasons for any differences between enrollment and the safety at-risk count. It lists 24 enrolled and 14 at risk for the safety entry, without explaining the difference. The safety entry contains limited event detail and no serious adverse-event terms.

A sample-size justification, interim analysis information, multiplicity procedures and sensitivity analyses are not reported in the registry record. These omissions prevent evaluation of the planned precision and the robustness of any analysis. The listed population is healthy volunteers, so the record does not establish that findings would apply to other populations. These limitations concern the information recorded and do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetics of Plasma Doravirine Once Daily Over 72 Hours Following Drug Intake Cessation in Healthy Volunteers — NCT03894124.
• Registry record last updated 2024-09-19; status last verified 2024-09.
• Results first posted 2024-09-19.
• 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 describes a completed phase 1, single-group study of plasma doravirine after daily intake ceased. Twenty-four participants were listed as enrolled. The intervention was Pifeltro® (doravirine 100mg) daily for 7 days, and the stated population was healthy volunteers.

The primary outcome was steady-state plasma concentrations through 72 hours post-dose, summarized as a geometric mean with a 95% confidence interval. The record specifies pre-dose sampling and post-dose measurements at 2, 4, 8, 12, 24, 30, 36, 48, 60 and 72 hours. Numerical primary-outcome results are not reported in the registry record.

The registry lists treatment-emergent adverse events as a secondary outcome. Its safety entry records 14 participants at risk, zero with serious adverse events, six with other adverse events and zero deaths. The record does not explain the safety denominator or provide detailed event descriptions. A detailed statistical analysis plan and missing-data methods are not reported in the registry record.