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 Pharmacokinetics and Safety of Double-dose Dolutegravir When Used With Rifapentine for HIV-associated Tuberculosis (NCT05630872), a na phase 2 study. The primary outcome is Model-simulated 5th Percentile and Corresponding 95% Confidence Interval of DTG Cmin at 50 mg BID When Co-administered With Daily RPT 1200 mg Plus HZM.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05630872 |
| Phase | Phase 2 |
| Condition | HIV-associated Tuberculosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
The study addressed whether dolutegravir 50 mg taken twice daily could provide adequate drug exposure when used with daily rifapentine 1200 mg for HIV-associated tuberculosis. Its primary pharmacokinetic question focused on the lower tail of the concentration distribution: the model-simulated 5th percentile of dolutegravir minimum concentration, or Cmin, and its corresponding 95% confidence interval. The registry record states the hypothesis, but does not report the numerical endpoint estimate.
Population
Adults with HIV and newly diagnosed drug-susceptible tuberculosis who were not currently receiving antiretroviral therapy. The primary endpoint population is described as participants with pharmacokinetic data available.
Intervention
The described strategy included dolutegravir 50 mg orally twice daily, approximately 12 hours apart, with TDF/3TC, alongside rifapentine-based tuberculosis therapy. The registry also lists dolutegravir 50 mg once daily and the regimens 2HPZM and 2HPM.
Comparator
No randomized control group is described. The study is recorded as a single-group trial with no masking; the listed interventions do not establish a like-for-like comparison.
Primary question
What lower-tail dolutegravir Cmin does a pharmacokinetic model predict at 50 mg twice daily with daily rifapentine 1200 mg plus HZM, and how uncertain is that estimate?
The primary endpoint is a model-based exposure measure, not a clinical outcome such as viral suppression. The registry summary describes viral suppression as the rationale for the hypothesis, but the primary endpoint listed is drug concentration. Whether the exposure measure met a prespecified target, and the numerical model result, are not reported in the registry record.
3. Trial Design
This was a Phase 2, completed, single-group study with an enrollment of 30. The condition was HIV-associated tuberculosis. The registry records allocation as not applicable and masking as none, so the design is not a randomized, masked comparison. The record does not describe a concurrent control group or a treatment-effect estimate comparing groups.
The population is described as adults with HIV and newly diagnosed drug-susceptible tuberculosis who were not currently on antiretroviral therapy. At study entry, participants received daily rifapentine-moxifloxacin with isoniazid and pyrazinamide for 8 weeks, followed by daily rifapentine-moxifloxacin with isoniazid for 9 weeks. The record refers to these phases as 2HPZM and 2HPM. Dolutegravir-based antiretroviral therapy at 50 mg twice daily was started after 6 weeks of tuberculosis therapy. The available arm description ends before the treatment details are complete, so the full schedule and duration of each antiretroviral regimen are not reported in the registry record.
The intervention list also names dolutegravir 50 mg once daily with TDF/3TC, but the record does not explain its relationship to the twice-daily regimen or define a separate comparison. The listed interventions should therefore not be read as evidence of randomized treatment arms. The stated study hypothesis concerned twice-daily dolutegravir exposure with rifapentine; the record identifies no control-based efficacy question.
The study began on 2024-02-13, reached primary completion on 2025-05-07, and is recorded as completed. A detailed protocol, formal sample-size justification, and the full statistical analysis plan 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
| Stage | Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART |
|---|---|
| STARTED | 30 |
| COMPLETED | 28 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART |
|---|---|
| Physician Decision | 1 |
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Participants with pharmacokinetic data available.
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 participants
| Characteristic | Unit | Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART |
|---|---|---|
| Participants analysed | 30 | |
| Age, Continuous | years | 35 (32 to 38) |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 27 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: South Africa | Participants | 27 |
| Region of Enrollment: Thailand | Participants | 3 |
| BMI: Underweight: <18.5 kg/m2 | Participants | 9 |
| BMI: Healthy Weight: 18.5 to <25 kg/m2 | Participants | 19 |
| BMI: Overweight: 25 to <30 kg/m2 | Participants | 1 |
| BMI: Obese: 30+ kg/m2 | Participants | 1 |
| HIV-1 RNA | log10 copies/mL | 4.99 (4.19 to 5.38) |
| CD4 | 10^6 CD4 cells/L | 185 (135 to 357) |
| Tuberculosis (TB) regimen prior to study entry: HRZE | Participants | 18 |
| Tuberculosis (TB) regimen prior to study entry: None | Participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Model-simulated 5th Percentile and Corresponding 95% Confidence Interval of DTG Cmin at 50 mg BID When Co-administered With Daily RPT 1200 mg Plus HZM, measured over Measured at week 8 and week 21. Samples were drawn pre-dose and at 1, 2, 4, 6, 8-10, and 24 hours (but prior to next dose) post-dosing..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | ug/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the model-simulated 5th percentile of dolutegravir minimum concentration, Cmin, at 50 mg twice daily when co-administered with daily rifapentine 1200 mg plus HZM. The registry describes the corresponding 95% confidence interval as the measure of uncertainty. Measurements contributing to the pharmacokinetic analysis were scheduled at week 8 and week 21, with samples collected before dosing and at 1, 2, 4, 6, 8-10, and 24 hours after dosing, before the next dose.
Cmin represents the low point in a concentration profile over a dosing interval. In general, examining a lower percentile rather than only an average can help characterize the part of a modeled population distribution with comparatively low exposure. It is relevant to the stated hypothesis because the study concerned whether the twice-daily regimen would maintain adequate exposure alongside rifapentine. The endpoint is nevertheless a pharmacokinetic quantity, not a direct measure of viral suppression or tuberculosis outcome.
The record says the concentration distribution was simulated using a nonlinear mixed-effects model and that the final model simulated 10000 individuals while incorporating parameter uncertainty. Thus, the 5th percentile is a modeled population quantity, not a concentration directly observed in one participant. Neither the numerical percentile nor its confidence interval is reported in the registry record, and no exposure threshold for interpreting it is stated there.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes the intended analysis but does not report the primary endpoint result. It gives the target quantity—the model-simulated 5th percentile of dolutegravir Cmin at 50 mg twice daily with daily rifapentine 1200 mg plus HZM—and says a corresponding 95% confidence interval was to be reported. Without the estimate, interval limits, or a stated exposure threshold, the posted information does not establish whether the modeled lower-tail concentration was considered adequate. No numerical conclusion about the primary pharmacokinetic question can be drawn from the information in the record.
The study hypothesis concerned adequate drug exposures to maintain viral suppression. That rationale should be distinguished from the listed primary endpoint. A concentration model can characterize predicted exposure; it does not, by itself, report whether viral suppression was maintained. The secondary outcome list includes pharmacokinetic measures such as Cmin, maximum concentration, area under the concentration-time curve, clearance, and terminal half-life, as well as adverse-event outcomes. Their presence in the list does not establish the values observed or the conclusions reached.
The study is recorded as single-group, with allocation not applicable and no masking. Consequently, the design does not support a randomized comparison between treatment groups as described in the registry. Any interpretation should remain focused on the observed or modeled experience under the study regimen and avoid treating the listed once-daily and twice-daily interventions as matched arms. The record does not provide a comparative estimate that would separate regimen effects from other influences.
In general, a confidence interval expresses uncertainty around an estimate under the model and analysis used. A narrower interval indicates greater precision for that modeled quantity, while a wider interval indicates more uncertainty. The registry says the simulation incorporated parameter uncertainty, but it does not state the interval limits or the precise procedure used to construct the interval. The range of uncertainty therefore cannot be assessed from the numerical information available in the record.
The adverse-event summary reports 2 participants with serious adverse events among 30 at risk, 18 with other adverse events among 30 at risk, and 0 deaths. These are descriptive counts in a single group, not evidence from a comparative safety analysis. The serious-event term list includes Clostridium difficile colitis, gastroenteritis, meningitis, and arthropod bite, each listed as 3.3%. The record does not provide enough detail to infer causality, event timing, or comparative risk.
Overall, the registry record documents the study question, design, endpoint definition, model approach, and selected safety counts, but not the numerical primary result. That distinction matters: a defined analysis is not the same as a reported finding, and a missing result should not be replaced by an assumption about its direction or magnitude.
9. Statistical Methods Explained
The primary analysis was based on pharmacokinetic modeling. The registry states that pharmacokinetic parameters were estimated with nonlinear mixed-effects modeling using FOCE-I, and that the final model was then used to simulate a concentration distribution. These are model-based steps: the endpoint is not simply a summary of a single directly observed concentration, but a predicted percentile derived from the fitted model.
What does nonlinear mixed-effects modeling do?
In general, a nonlinear mixed-effects model describes how a measured quantity changes with time or other inputs while allowing for both population-level patterns and differences among individuals. The nonlinear part allows the relationship between model parameters and the concentration profile to take a nonlinear form. The mixed-effects part represents shared features of the population alongside individual variation. This framework is commonly used for pharmacokinetic data, where concentrations are measured at multiple times and the analysis seeks to characterize concentration profiles and parameters such as clearance.
FOCE-I is the estimation approach named in the registry. In general, this approach estimates model parameters while accounting for individual-level variation; the interaction component allows the residual-error structure to interact with the individual effects in the estimation. The registry does not report the full model specification, residual-error model, parameter estimates, diagnostics, or criteria used to select the final model. Those details are not reported in the registry record.
How was the lower-tail endpoint generated?
The final model was used to simulate 10000 individuals. The reported target was the simulated 5th percentile of Cmin, together with a 95% confidence interval. In general, a percentile describes a position in a distribution: the 5th percentile marks a lower-tail point in the modeled concentration distribution. It does not mean that every participant had that concentration, nor is it the observed minimum across the enrolled participants. The numerical percentile is not reported in the registry record.
The record says the simulations incorporated parameter uncertainty. In general, model parameters are estimated from data and are not known without uncertainty; carrying parameter uncertainty into simulation helps represent how uncertainty in fitted parameters affects the modeled endpoint. It does not automatically account for every possible source of uncertainty, such as misspecification of the model or limitations in the data. The record does not describe the exact procedure used to obtain the confidence interval, so its construction cannot be characterized more specifically.
Which covariates were included?
The listed covariates were fat-free mass on disposition parameters, rifapentine on clearance and bioavailability, and baseline unconjugated bilirubin on clearance. In general, a covariate model represents how participant characteristics or co-administered drugs relate to model parameters. Including a covariate can help describe systematic differences in pharmacokinetics, but the registry does not report the estimated size or uncertainty of any covariate relationship. It also does not report whether other candidate covariates were evaluated or how the listed covariates were selected.
How do the sampling schedule and steady-state assumption fit in?
Samples were scheduled at week 8 and week 21, before dosing and at 1, 2, 4, 6, 8-10, and 24 hours after dosing, with the 24-hour sample taken before the next dose. The endpoint description says measurements were taken at steady state, assumed to be achieved after at least 5 half-lives. In general, steady state describes the condition in which repeated dosing has produced a stable concentration pattern across dosing intervals. The registry states the assumption but does not report participant-specific confirmation of steady state.
The time points provide observations across the dosing interval that can inform a concentration-time profile. In general, sampling across time is important because a model estimates the shape of a profile as well as quantities such as its minimum, maximum, and overall exposure. The registry does not report the number of samples actually available at each time point, deviations from the planned schedule, or the handling of measurements below assay limits.
What can the model result establish?
A model-based percentile can describe predicted exposure under the assumptions of the fitted model and the analyzed data. It should be interpreted alongside the model’s uncertainty, its fit to observed concentrations, and the definition of the target population. The registry identifies the population for the primary analysis as participants with pharmacokinetic data available, but provides no diagnostics or numerical endpoint estimate. Accordingly, readers cannot assess the model’s fit, reproduce the estimate, or judge its precision from the registry record alone.
The endpoint is also distinct from clinical outcomes. A modeled dolutegravir concentration is not equivalent to a measured viral suppression outcome, and the registry’s stated hypothesis about maintaining suppression does not substitute for a reported clinical result. The statistical method answers a pharmacokinetic modeling question only to the extent that the fitted model and its results are reported. In this record, the method is described, but the primary numerical output is not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 5 analyses. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting several endpoints together. Without such information, the record does not establish whether any formal control of false-positive findings was planned across multiple analyses. The absence of a reported adjustment does not show that none was used; it means that the approach is not reported in the registry record.
The primary endpoint population is described as participants with pharmacokinetic data available. The enrollment is 30, but the record does not state how many participants contributed to the primary model, how many had complete pharmacokinetic profiles, or how missing measurements were handled. It does not report exclusions, reasons for missing data, imputation methods, or sensitivity analyses addressing missingness. The number enrolled therefore should not be assumed to equal the number analyzed for every endpoint.
The record also does not define analysis populations for the secondary pharmacokinetic and safety outcomes, or explain whether all enrolled participants were included in each analysis. A detailed statistical analysis plan, including missing-data procedures and multiplicity methods, is not reported in the registry record. These omissions limit assessment of how the planned analyses related to the final reported results; in this case, the numerical primary result itself is also not reported.
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 |
|---|---|---|---|
| Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART | 2 | 30 | 6.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART | 0 of 30 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART | 18 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART |
|---|---|---|
| Clostridium difficile colitis | Infections and infestations | 1 of 30 |
| Gastroenteritis | Infections and infestations | 1 of 30 |
| Meningitis | Infections and infestations | 1 of 30 |
| Arthropod bite | Injury, poisoning and procedural complications | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adults With HIV and Newly Diagnosed DS-TB Not Currently on ART |
|---|---|---|
| Blood pressure increased | Investigations | 3 of 30 |
| Abnormal loss of weight | Metabolism and nutrition disorders | 3 of 30 |
| Headache | Nervous system disorders | 3 of 30 |
| Normocytic anaemia | Blood and lymphatic system disorders | 2 of 30 |
| Upper respiratory tract infection | Infections and infestations | 2 of 30 |
| Haemoglobin decreased | Investigations | 2 of 30 |
| Weight decreased | Investigations | 2 of 30 |
| Hypoglycaemia | Metabolism and nutrition disorders | 2 of 30 |
| Neuropathy peripheral | Nervous system disorders | 2 of 30 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 30 |
Serious events with the highest arm-level rate: clostridium difficile colitis (3.3%), gastroenteritis (3.3%), meningitis (3.3%), arthropod bite (3.3%).
The adverse-event summary describes one study group of 30 participants at risk. It records 2 participants with serious adverse events and 18 with other adverse events; 0 deaths are recorded. These are participant counts, not event totals, and the registry summary does not provide a comparison group. The counts should therefore be read descriptively rather than as estimates of a treatment difference.
The listed serious-event terms are Clostridium difficile colitis, gastroenteritis, meningitis, and arthropod bite, each reported as 3.3%. Those percentages are reproduced as recorded. The summary does not report event onset, duration, recurrence, severity beyond the serious classification, or investigator assessment of relatedness. It also does not state whether individual participants experienced more than one serious event, so the listed terms should not be added or treated as distinct participants.
Other safety outcomes named in the registry include grade 3 or higher adverse events, rifamycin hypersensitivity, and drug-induced liver injury. Their numerical results are not reported in the registry record. General caution applies when reading safety data from a single group: descriptive counts alone cannot establish whether an event was caused by a regimen or how its frequency compares with another treatment.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2 study evaluated a pharmacokinetic question involving twice-daily dolutegravir with rifapentine-based tuberculosis treatment in adults with HIV and newly diagnosed drug-susceptible tuberculosis. It identifies the primary endpoint as a modeled lower-tail concentration measure and describes the nonlinear mixed-effects approach used to generate it. It also reports selected safety counts for the study group.
The record does not report the numerical estimate for the primary endpoint or its 95% confidence interval. It therefore does not show the magnitude or precision of the modeled 5th percentile of Cmin. The stated hypothesis concerns exposure considered adequate to maintain viral suppression, but no threshold for adequacy or numerical assessment against such a threshold is reported. The registry information does not establish whether the hypothesis was supported.
The primary measure is pharmacokinetic rather than a direct clinical outcome. A modeled concentration distribution is not itself a report of viral suppression, tuberculosis response, or a comparative clinical benefit. Although the secondary outcomes list includes pharmacokinetic and safety measures, their numerical results are not reported in the registry record. The study’s completed status does not fill in those missing outcome results.
The single-group design also limits what can be learned comparatively. The record does not describe randomized allocation to a control regimen, and it does not provide a like-for-like treatment contrast. Consequently, the listed interventions should not be interpreted as randomized arms, and the descriptive safety counts cannot establish a difference in risk between regimens.
In general, the appropriate statistical interpretation separates the question a study set out to answer from the evidence actually reported. Here, the endpoint, population, modeling method, and some safety counts are described, but essential numerical primary results and analysis details are absent. Conclusions about the direction, size, or clinical importance of the primary result would go beyond what is reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for using a model-derived population percentile as its primary endpoint rather than relying on a single average concentration. In general, population percentiles can make the lower tail of a predicted distribution visible, which may be relevant when the scientific question concerns whether low exposures occur under a dosing strategy. The record defines this endpoint as the simulated 5th percentile of Cmin and pairs it with a 95% confidence interval.
The approach also makes uncertainty and model assumptions central to interpretation. A lower-tail estimate depends on the fitted concentration model, its covariate structure, the available sampling, and the assumptions used for simulation. The registry names the estimation method, simulation size, covariates, and steady-state assumption, but does not report model diagnostics or the numerical result. Those details are important because a sophisticated modeling method does not remove uncertainty about the data or model fit.
The design is single-group, so the statistical question is not a randomized comparison of regimens. This distinguishes a pharmacokinetic characterization from a causal treatment contrast. The registry summary connects the exposure hypothesis to maintaining viral suppression, but the listed primary endpoint is concentration-based; distinguishing surrogate pharmacokinetic measures from clinical outcomes is essential to avoid overstating what the analysis can establish.
Finally, this record illustrates the difference between describing an analysis plan and reporting its findings. The endpoint and methods are specified, yet the estimate, interval, and several secondary results are not reported. That limits independent assessment of precision and prevents readers from evaluating the primary result 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 main limitation for statistical interpretation is that the primary endpoint estimate and its confidence interval are not reported in the registry record. Without them, the magnitude and precision of the modeled lower-tail concentration cannot be assessed. The record also does not state a concentration threshold for adequacy, so the stated hypothesis cannot be evaluated from the reported endpoint definition alone.
The enrolled group contained 30 participants, and the primary analysis population is described as participants with pharmacokinetic data available. The number contributing to the model is not reported. Missing-data handling, assay-limit handling, protocol deviations, and sensitivity analyses are also not reported in the registry record. These gaps make it difficult to assess how representative the analyzed pharmacokinetic data were of the enrolled group.
The record gives selected modeling details, including FOCE-I, the covariates, and simulation of 10000 individuals with parameter uncertainty. It does not report the full model specification, parameter estimates, fit diagnostics, model selection process, confidence-interval construction, or external validation. The assumptions underlying the simulated percentile therefore cannot be fully evaluated from the registry record.
The design is single-group and unmasked, with no randomized comparison described. The intervention list includes both once-daily and twice-daily dolutegravir, but the record does not clarify their relationship or provide a comparison structure. The available arm description is incomplete. Finally, numerical results for listed secondary pharmacokinetic and safety outcomes are not reported. Together, these limitations constrain both reproducibility and interpretation of the study’s findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetics and Safety of Double-dose Dolutegravir When Used With Rifapentine for HIV-associated Tuberculosis — NCT05630872.
- Registry record last updated 2026-07-20; status last verified 2026-07.
- Results first posted 2026-07-20.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT05630872 is a completed Phase 2, single-group study with an enrollment of 30. It evaluated dolutegravir dosing alongside rifapentine-based tuberculosis therapy in adults with HIV and newly diagnosed drug-susceptible tuberculosis who were not currently receiving antiretroviral therapy. The primary endpoint was the model-simulated 5th percentile of dolutegravir Cmin at 50 mg twice daily with daily rifapentine 1200 mg plus HZM.
The registry describes nonlinear mixed-effects modeling with FOCE-I, a simulation of 10000 individuals incorporating parameter uncertainty, and specified covariates. It reports 2 participants with serious adverse events, 18 with other adverse events, and 0 deaths among the study group. The numerical primary endpoint, its confidence interval, detailed analysis populations, and many secondary results are not reported in the registry record.