A Study to Investigate the Pharmacokinetics of a Combined Oral Contraceptive When Given Alone and in Combination With GSK3036656 in Female Participants of Non-childbearing Potential Aged 18 to 65 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Investigate the Pharmacokinetics of a Combined Oral Contraceptive When Given Alone and in Combination With GSK3036656 in Female Participants of Non-childbearing Potential Aged 18 to 65 Years of Age (NCT06354257), a non-randomized phase 1 study. The primary outcome is Area Under the Plasma Drug Concentration (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) After a Single Dose of EE and LNG.

2. Clinical Question

The study’s stated purpose is to assess whether GSK3036656 affects a combined oral contraceptive containing ethinyl estradiol and levonorgestrel. The resulting pharmacokinetic information was intended to inform future studies on suitable contraceptive measures. This is a drug-drug interaction question: the focus is the measured drug exposure under the two treatment conditions, not a clinical pregnancy outcome or a comparison of contraceptive effectiveness.

The participants were described as healthy and of nonchildbearing potential, and the study concerned tuberculosis through its listed condition. The record describes a phase 1 investigation, so its focus is pharmacokinetic and safety characterization in the studied group. The posted record does not give a primary result from which to judge the direction or size of any difference in exposure.

3. Trial Design

This was a phase 1, open-label, fixed-sequence, one-way drug-drug interaction study. It was non-randomized and had no masking. The registry reports enrollment of 20 participants and lists the study as completed. The recorded start date is 2024-04-05 and the primary completion date is 2024-07-01.

The registry describes three treatment periods. In Treatment Period 1, participants received a dose of Microgynon on Day 1. In Treatment Period 2, they received GSK3036656 40 mg on Day 4, followed by 20 mg once daily from Day 5 to Day 14. The primary endpoint timeframe identifies Treatment Period 3 as the period in which Microgynon was given with GSK3036656, with the assessment on Day 15. The remaining details of the Treatment Period 3 regimen are not reported in the registry record.

A fixed sequence means the treatment conditions are administered in an ordered sequence rather than assigned at random. That structure permits within-participant pharmacokinetic observations under the specified conditions, but it does not make the comparison equivalent to a randomized trial. Period, sequence, and time-related influences may be difficult to separate from the treatment condition in a non-randomized design. The registry record does not report a separate randomized control group.

Open-label means the study was not masked. Masking is often used to limit expectations from influencing participant or investigator behavior and some assessments. For a concentration-based pharmacokinetic endpoint, laboratory measurement is central, but the registry does not describe laboratory blinding or other safeguards; those details are not reported in the registry record.

GlaxoSmithKline is listed as sponsor. The record lists Microgynon and GSK3036656 as the drug interventions. It does not report the rationale for the enrollment target, details of any interim analyses, or a full statistical analysis plan. Those omissions limit what can be concluded about how the design was selected and how the analysis was prespecified.

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: The Combined Participants Group includes all participants from the 3 treatment periods combined. This group was used to summarize Participant Flow and Baseline Characteristics in the study.

Treatment Period 1

Reasons for not completing this period:

Treatment Period 2

Reasons for not completing this period:

Treatment Period 3

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Pharmacokinetic (PK) Set which includes all the participants from the Safety Set (SS) who had at least 1 non-missing PK assessment. This population is defined according to the treatment actually received by the participants and comprises only those with the specified PK parameter available for summary computation.

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.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Plasma Drug Concentration (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) After a Single Dose of EE and LNG, measured over At Day 1 for the Treatment Period 1: Microgynon Group and at Day 15 for the Treatment Period 3: Microgynon + GSK3036656 Group.

The primary endpoint is the area under the plasma drug concentration-time curve from time zero extrapolated to infinity, abbreviated AUC(0-inf), after a single dose of ethinyl estradiol and levonorgestrel. Its unit is hour*picogram per milliliter (h*pg/mL). The registry specifies measurements at Day 1 in the Microgynon group during Treatment Period 1 and at Day 15 in the Microgynon plus GSK3036656 group during Treatment Period 3.

In general, an area under a concentration-time curve represents overall drug exposure over time. Extending the curve from the observed period to infinity estimates the remaining exposure after the last measured concentration. The record says this endpoint was calculated using non-compartmental analysis, a method that derives pharmacokinetic measures from the observed concentration-time data without requiring a specified compartment model.

Comparing exposure after Microgynon alone with exposure after Microgynon in combination with GSK3036656 addresses whether coadministration is associated with a change in the measured exposure to either contraceptive component. AUC is useful for this purpose because it summarizes concentration across time rather than relying on a single concentration measurement. The registry identifies geometric mean as the summary parameter and geometric coefficient of variation as the measure of dispersion.

The registry record does not report the endpoint values, variability estimates, confidence intervals, or a statistical test for the primary comparison. Therefore, the endpoint definition and assessment schedule can be described, but the size and precision of any observed difference cannot be interpreted from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names a pharmacokinetic endpoint and some analysis-population details, but does not provide a complete statistical analysis plan or the primary outcome estimates. The following concepts explain how such measures are generally interpreted; they do not fill in analyses or results absent from the registry record.

What does AUC measure?

In general, area under the concentration-time curve measures cumulative drug exposure across a specified time interval. AUC(0-inf) begins at time zero and extends the estimate to infinity. The portion beyond the last observed concentration is extrapolated, so the resulting estimate depends partly on the observed concentration profile and the terminal portion of that profile. The registry states that non-compartmental analysis was used. In general, non-compartmental methods summarize observed concentration-time data using their timing and measured concentrations rather than assuming a particular compartment structure.

The primary endpoint applies this measure to ethinyl estradiol and levonorgestrel following Microgynon administered alone and with GSK3036656. AUC is informative for a drug-drug interaction question because a change in overall exposure may occur even when a single concentration measurement does not capture the full profile. The record does not describe the sampling schedule or the detailed procedure used to estimate the terminal extrapolation.

Why report geometric means?

In general, pharmacokinetic measures can have a right-skewed distribution, with some observations larger than others by a multiplicative rather than an additive pattern. A geometric mean is calculated by working on a logarithmic scale and converting the summary back to the original scale. It is often a suitable summary for positive exposure measures. The geometric coefficient of variation conveys relative variability on a multiplicative scale; it is not the same as a standard deviation in the original units.

These summaries describe the distribution of measured exposure, but they are not by themselves a complete treatment comparison. Interpretation typically also depends on a contrast between conditions and its uncertainty. The registry record does not report the primary geometric mean values, geometric coefficients of variation, estimated contrast, confidence interval, or test result. No effect size or precision statement can therefore be derived from the record.

What does a confidence interval communicate?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not by itself establish that a difference is clinically important, and its meaning depends on the estimand, model, and interval construction. No confidence interval for the primary endpoint is reported in the registry record.

Similarly, a p-value is a measure of how compatible the observed data are with a specified statistical null model, under the assumptions used for the test. It is not a measure of the probability that a treatment effect is true, and it does not communicate the size of an effect. No primary p-value or testing procedure is reported in the registry record.

How does the sequence affect interpretation?

The study is non-randomized, open-label, and fixed-sequence. In general, randomized assignment helps balance measured and unmeasured factors across treatment groups, while a fixed sequence does not provide that protection between treatment conditions. When the same participants receive successive conditions, their observations may be related; sequence and period effects may also matter. The record identifies the sequence and assessment periods but does not report a model for paired observations, period effects, carryover, or other adjustments. These elements should not be assumed.

Because the comparison is not randomized, it should not be characterized as a like-for-like control comparison. The treatment-period labels describe when participants received the regimens; they do not imply independent, randomized arms. The registry does not report whether any washout period was used, so no washout assumption can be made.

What is the role of the planning illustrations?

Any sample-size illustrations associated with the observed effect are planning calculations, not observed trial results and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record characterizes non-time-to-event sample-size outputs as participants per arm for 80% or 90% power, and time-to-event outputs as a total number of events. It does not report the trial's own sample-size justification. The observed endpoint effect and the numerical planning outputs are not reported in the registry record, so their values cannot be.

More generally, planning illustrations depend on the assumed effect and statistical model. They do not show the probability that the completed study detected an effect, and they do not replace estimates with uncertainty intervals. The trial's enrollment of 20 is an observed design fact; it should not be confused with a sample-size justification or with a claim about power.

What analyses are not documented?

The record lists 18 outcome measures and 4 analyses, but does not specify the full set of statistical methods for the primary endpoint. In particular, the model, treatment contrast, handling of repeated observations, confidence-interval method, significance threshold for the endpoint, and any sensitivity analyses are not reported in the registry record. The existence of multiple outcomes makes it important to know whether and how multiplicity was addressed, but that strategy is not reported either. Consequently, the endpoint description supports a clear explanation of what was measured, not a reconstruction of the inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures and 4 analyses. Several secondary outcomes concern GSK3036656 exposure with ethinyl estradiol and levonorgestrel, and others concern ethinyl estradiol and levonorgestrel alone and with GSK3036656. Serious adverse events are also listed as an outcome. The record does not specify a hierarchy among outcomes, a multiplicity adjustment, or whether any findings were intended to be confirmatory. A strategy for controlling the chance of false-positive findings across multiple comparisons is not reported in the registry record.

The primary outcome description identifies a Pharmacokinetic Set, which includes participants from the Safety Set with at least 1 non-missing pharmacokinetic assessment. It also says that the population is defined according to treatment actually received, but the remainder of the definition is incomplete in the record. The number of participants included in the primary endpoint analysis is not reported in the registry record.

Missing-data methods are not reported in the registry record. The record does not explain how missing concentration samples, incomplete profiles, or endpoints that could not be estimated were handled. It also does not report sensitivity analyses assessing the influence of missing pharmacokinetic measurements. The safety counts at risk vary by treatment period, but those counts alone do not explain the missingness or analysis population for the primary endpoint.

The rationale for the enrollment target, interim-analysis plans, and a complete statistical analysis plan are not reported in the registry record. Without those details and the numerical primary results, it is not possible to evaluate the planned inferential framework or determine whether the analyses followed a prespecified strategy.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports safety counts separately for each treatment period. In the Microgynon group, 20 participants were at risk for serious adverse events and 0 were affected; 20 were at risk for other adverse events and 4 were affected. In the GSK3036656 group, the corresponding counts were 19 at risk and 0 affected for serious adverse events, and 19 at risk and 1 affected for other adverse events. In the Microgynon plus GSK3036656 group, 18 were at risk and 0 were affected by serious adverse events, while 18 were at risk and 1 was affected by other adverse events.

No deaths are listed in any treatment period, and no serious adverse event terms are listed. These counts are descriptive. The changing numbers at risk reflect the record's separate period-specific safety groups; they are not a randomized comparison and should not be read as evidence that one regimen has a higher or lower risk than another. The registry does not provide event-level detail for the other adverse events in the information.

A zero count in this study means that no serious adverse events were recorded in the listed group; it does not establish that such events cannot occur. With no reported comparative analysis or detailed event descriptions, the safety figures do not support a broad conclusion about relative safety.

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

The study addresses a focused pharmacokinetic question: whether exposure to ethinyl estradiol and levonorgestrel, measured by AUC(0-inf), differs when Microgynon is administered alone or in combination with GSK3036656. The registry record specifies the endpoint, assessment periods, summary parameter, and population concept. These details clarify what investigators intended to measure.

But the endpoint results are not reported in the registry record. There is no reported estimate of exposure under either condition, no treatment contrast, and no interval or test result. It is therefore not possible to state whether exposure was higher, lower, or similar, or how precisely any difference was estimated. The absence of a reported result is not evidence that there was no difference.

The design also limits what a comparison can establish. Participants received treatments in a non-randomized fixed sequence, without masking. This does not provide the same basis for causal comparison as randomized allocation, and any observed contrast would need to be interpreted in light of the sequence and the absence of a randomized control group. The record does not describe adjustments for period or sequence effects.

The study's stated purpose was to generate information to inform future studies on suitable contraceptive measures. Its population was healthy female participants of nonchildbearing potential aged 18 to 65 years, so the record does not establish findings in other populations. Nor does the pharmacokinetic endpoint directly report contraceptive effectiveness or a clinical outcome.

The safety data are also limited to the recorded counts. They show no serious adverse events and no deaths in the listed period-specific groups, alongside the reported counts for other adverse events. These observations should be read as descriptive rather than as a definitive comparison of safety. Overall, the record documents the study design and intended pharmacokinetic assessment, but leaves the primary result and its precision unavailable.

13. Why This Trial Matters Statistically

Drug-drug interaction studies often ask whether one medicine changes the exposure of another. This study frames that question using a combined oral contraceptive containing ethinyl estradiol and levonorgestrel, and GSK3036656. AUC(0-inf) is a pharmacokinetic summary that captures exposure across time, making it a relevant endpoint for describing a possible interaction.

Statistically, the fixed-sequence design raises important interpretive considerations. Repeated observations from participants across treatment periods can be informative, but treatment is not randomized across concurrent groups. Treatment condition and period are therefore linked in the sequence, and the record does not report a model that separates their contributions. Recognizing this distinction prevents the comparison from being mistaken for a randomized control contrast.

The record also illustrates why an endpoint definition is not a result. It specifies geometric means and geometric coefficients of variation, but does not report their values or a treatment contrast. Without those estimates and measures of uncertainty, readers cannot assess the magnitude or precision of the pharmacokinetic comparison. Clear reporting of point estimates and uncertainty is central to statistical interpretation.

Finally, the study has a stated role in informing future research, while its enrollment is 20 and its listed population is specific. The safety counts are descriptive, and the multiple outcome measures make the unreported multiplicity strategy relevant to interpretation. These features show why design, analysis, precision, and reporting all matter alongside the pharmacokinetic endpoint itself.

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 primary limitation for interpreting the study is that the registry record does not report the primary endpoint values or the statistical comparison. Without those results, the direction, size, and precision of any change in ethinyl estradiol or levonorgestrel exposure cannot be assessed.

The comparison is non-randomized and fixed-sequence. Treatment condition is tied to treatment period, and the registry does not report an analysis addressing possible period or sequence effects. The record also does not report whether a washout period was used. The study was open-label and unmasked; details about laboratory blinding are not reported in the registry record.

The full description of Treatment Period 3 is not reported in the registry record. The endpoint timeframe identifies Microgynon plus GSK3036656 on Day 15, but the complete regimen for that period is not available in the record. The primary analysis population definition is also incomplete, and the number contributing to the primary endpoint is not reported.

The record does not report missing-data procedures, the detailed statistical model, multiplicity handling, interim analyses, or the statistical analysis plan. The enrollment target's justification is not reported. These gaps prevent assessment of how the design and analysis were planned and how robust the primary estimate would be to alternative assumptions.

The safety counts are small descriptive summaries, with no serious adverse events or deaths listed, and limited event detail for other adverse events. The findings concern healthy female participants of nonchildbearing potential aged 18 to 65 years and should not be generalized beyond the recorded study population without additional evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Investigate the Pharmacokinetics of a Combined Oral Contraceptive When Given Alone and in Combination With GSK3036656 in Female Participants of Non-childbearing Potential Aged 18 to 65 Years of Age — NCT06354257.
• Registry record last updated 2025-08-26; status last verified 2025-08.
• Results first posted 2025-08-26.
• 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

NCT06354257 is a completed phase 1, open-label, non-randomized, fixed-sequence drug-drug interaction study sponsored by GlaxoSmithKline. The record lists enrollment of 20 healthy female participants of nonchildbearing potential aged 18 to 65 years. It evaluates Microgynon alone and with GSK3036656.

The primary endpoint is AUC(0-inf) for ethinyl estradiol and levonorgestrel after a single dose, assessed on Day 1 in Treatment Period 1 and Day 15 in Treatment Period 3. The registry specifies geometric means and geometric coefficients of variation, but the primary endpoint estimates and comparison results are not reported in the registry record.

The listed safety groups report 0 serious adverse events and 0 deaths in each treatment period. Other adverse events were recorded for 4 participants in the Microgynon group, 1 in the GSK3036656 group, and 1 in the Microgynon plus GSK3036656 group. The study's design and endpoint are described, but the missing primary results and incomplete analysis details limit statistical interpretation.