A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range (NCT05671653), a non-randomized phase 1 study. The primary outcome is Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Midazolam in Periods 1, 4 and 7.

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label study with non-randomized allocation and a parallel model comprising two cohorts. The registry record describes a fixed sequence within each cohort, rather than random assignment to treatment groups. Enrollment was 32. The study began on 2023-01-19, had a primary completion date of 2023-11-03, and is listed as terminated. The reason for termination is not reported in the registry record.

Cohort 1 enrolled otherwise healthy adult female participants with obesity. Its nine-period sequence assessed single-dose pharmacokinetics of midazolam and omeprazole together, and of an oral contraceptive containing LE and EE, in relation to PF-07081532 treatment. The sequence included titration to 80 mg once daily and subsequently to 260 mg once daily. Midazolam was assessed in Periods 1, 4, and 7 for the primary endpoint; the periods corresponded to baseline assessment and assessments during the two PF-07081532 dose levels. The registry record does not report the length of periods, washout arrangements, or other details needed to evaluate possible period or carryover effects.

Cohort 2 assessed single-dose midazolam pharmacokinetics before and during semaglutide treatment, titrated to 2.4 mg once weekly, in a four-period sequence. This cohort was not the randomized control group for Cohort 1: it examined a different drug and had a different period structure. The study's primary endpoint is specific to Cohort 1, while Cohort 2's midazolam assessment is listed among secondary outcomes.

The record lists 48 outcome measures and 9 analyses. It does not describe the complete statistical analysis plan, recruitment by cohort, or the number of participants who completed each sequence. Consequently, enrollment alone does not establish how many observations contributed to each endpoint.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: This study was a Phase 1, open-label, fixed-sequence study conducted with 2 cohorts. 16 participants were enrolled in Cohort 1 with 9 periods, 16 participants were enrolled in Cohort 2 with 4 periods.

Only the first 6 of 13 groups are shown.

Cohort 1 Period 1 - Treatment

Cohort 1 Period 2 - Treatment

Cohort 1 Period 3 - Treatment

Cohort 1 Period 4 - Treatment

Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 dose of midazolam, and had at least 1 of the PK parameters of interest calculated were included in the analysis.

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 enrolled participants who received at least 1 dose of study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Cohort 1: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Midazolam in Periods 1, 4 and 7, measured over For Cohort 1 Periods 1, 4, and 7: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours post midazolam dose on Day 1 of each period.

The primary endpoint is midazolam AUCinf in Cohort 1 during Periods 1, 4, and 7. AUCinf is the area under the plasma concentration-time profile from the time of dosing, extrapolated to infinite time. It is a pharmacokinetic measure of overall systemic exposure over time, rather than a measure of a clinical outcome. The record states that midazolam was administered on Day 1 in each of these periods, with blood samples collected before dosing and at prespecified times through 24 hours after dosing.

Pharmacokinetic studies use exposure measures such as AUCinf to describe how drug concentrations change after administration. Comparing the measure across periods can address whether the recorded exposure differs when midazolam is administered in the presence of PF-07081532 at the studied dose levels. This is a general explanation of the endpoint's role; it does not establish that a difference occurred in this study.

The registry record specifies a geometric mean as the summary parameter and geometric coefficient of variation as the dispersion measure. These summaries describe a distribution on a multiplicative scale, which is commonly used for pharmacokinetic measurements. The numerical geometric means, variability estimates, period comparisons, and confidence intervals are not reported in the registry record. Thus the endpoint definition is available, but the magnitude and precision of the observed pharmacokinetic results cannot be evaluated from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does AUCinf represent?

AUCinf is the area under the plasma concentration-time profile from the dosing time, extended to infinite time by extrapolation. In general, area under the curve captures overall exposure across the measured concentration profile. The extrapolated portion is an estimate beyond the last measured concentration, so interpretation depends on the pharmacokinetic methods and data quality. Details of the extrapolation procedure and its adequacy are not reported in the registry record. The endpoint is expressed in nanogram*hour/milliliter (ng*hr/mL).

Why use a geometric mean?

The registry record identifies the geometric mean as the primary endpoint summary and the geometric coefficient of variation as its dispersion measure. In general, pharmacokinetic measurements often vary multiplicatively: one participant's value may be several-fold another's, rather than differing by a constant additive amount. A geometric mean summarizes positive values on a multiplicative scale. The geometric coefficient of variation describes relative spread on that scale, rather than giving an absolute spread in the endpoint's measurement units.

These summaries do not by themselves show whether two periods differ. A period comparison needs an estimate of the contrast and a description of its uncertainty. In general, a confidence interval gives a range of values compatible with the observed data and analysis assumptions; a narrower interval indicates greater precision than a wider interval. Numerical estimates and confidence intervals for the primary endpoint are not reported in the registry record, so neither effect magnitude nor precision can be judged.

How does the fixed sequence affect interpretation?

The record describes Cohort 1 as an open-label, nine-period, fixed-sequence study and Cohort 2 as an open-label, four-period, fixed-sequence study. In a fixed sequence, the order of assessments is specified rather than randomized. When the same participant is assessed under multiple conditions, the measurements may be correlated. In general, an analysis should account for the repeated-measures structure and consider whether period effects or carryover could influence the comparison. The registry record does not report the model, covariance structure, period-effect handling, or carryover assessment. It would therefore be inappropriate to assume a particular statistical approach.

Open-label means that treatment masking was absent. For a laboratory pharmacokinetic endpoint, measurements are more objective than many subjective outcomes, but open-label status does not remove possible design or conduct effects. It is still relevant to interpretation alongside the fixed sequence and absence of random allocation.

What does the analysis population include?

The primary endpoint population is defined as participants who received at least one dose of midazolam and had at least one of the pharmacokinetic parameters of interest calculated. This is an endpoint-specific population definition. It does not establish how many participants met the criteria, whether all enrolled participants were included, or how missing pharmacokinetic measurements were handled. Those counts and procedures are not reported in the registry record.

What can planning calculations establish?

The study record includes a description of planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are illustrations of sample sizes under stated assumptions, not observed power and not evidence that the original study was designed with those assumptions. The illustration's numerical sample-size outputs are not reported in the registry record. In general, assumed effect size and variability strongly affect planning estimates; assumptions derived from an observed effect can be uncertain, especially when the observed estimate is imprecise.

The record also states that the study is non-randomized and that the arms are not a like-for-like control comparison. Thus a calculation framed as equal allocation between two arms should not be read as proof that this trial had two randomized arms. The design details and the planning illustration answer different questions.

Why does over-dispersion matter?

Over-dispersion is a general statistical concern when observed variability exceeds what a chosen model assumes. If a model underestimates variability, uncertainty intervals can be too narrow and tests can appear more conclusive than warranted. For continuous pharmacokinetic outcomes, the relevant assumptions concern the distribution and variability of measurements or transformed measurements. The registry record does not report diagnostics or a model assessment, so no claim can be made about whether over-dispersion occurred in this study.

More broadly, a statistically significant result, if reported, would not by itself describe the size or practical importance of an exposure change. Conversely, a non-significant result would not establish equivalence or absence of an effect without an appropriate equivalence framework and sufficiently precise estimates. The record does not report a prespecified equivalence margin or numerical primary results. These are general principles and not conclusions about the study's unreported findings.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 48 outcome measures and 9 analyses, including pharmacokinetic outcomes, adverse-event outcomes, laboratory abnormalities, body-weight change, and psychological assessments. With multiple outcomes or comparisons, the chance of at least one apparently notable result can increase if each is tested separately. In general, a statistical plan may address multiplicity by identifying primary and secondary questions in advance or by adjusting inference across tests. Whether and how this study handled multiplicity is not reported in the registry record.

The primary endpoint is identified as Cohort 1 midazolam AUCinf across Periods 1, 4, and 7. However, the registry record does not report the full hierarchy of hypotheses, prespecified contrasts, multiplicity adjustment, or whether secondary analyses were considered confirmatory or exploratory. It also does not describe interim analyses or stopping rules. No such procedures should be inferred from the number of outcomes or analyses listed.

The primary analysis population includes participants who received at least one dose of midazolam and had at least one relevant pharmacokinetic parameter calculated. The record does not report the number included in that analysis, the number excluded, or the reasons for missing or unusable measurements. It does not describe imputation, sensitivity analyses, or how incomplete period sequences were handled. In a repeated-period study, missing measurements can reduce the information available for within-participant comparisons; in general, the impact depends on why data are missing and the analysis approach.

Enrollment and outcome listings should not be mistaken for complete analysis denominators. The safety data show changing numbers at risk across some periods, but the record does not explain the participant flow or missingness behind those counts. The statistical plan, detailed multiplicity approach, and missing-data procedures are not reported in the registry record.

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 safety listings give zero serious adverse events in every reported period group, and zero deaths in every listed group. The reported risk sets are period-specific: most groups list 16 participants at risk, while later groups in the sequences list smaller numbers. These are not necessarily the same number of participants contributing throughout every period, and the registry record does not give a complete participant-flow explanation.

The listings also report participants with other adverse events. Counts range across the period groups, including during titration periods and periods when study medicines were given together. These counts should be read as period-level records, not added across periods to estimate the number of unique participants affected. The same participant could have been assessed in multiple periods, and the record does not explain whether events continued across periods or were counted again.

The safety data are descriptive. The study was open-label and non-randomized, and the listed groups represent different points in treatment sequences rather than like-for-like randomized arms. The counts therefore do not establish that a treatment caused an event or that one regimen had a higher risk than another. The registry record lists no serious adverse-event terms and does not report additional context about event timing, duration, or clinical assessment.

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

The record establishes that the study was designed to assess pharmacokinetic effects of PF-07081532 and semaglutide on selected medicines in healthy adult female participants with obesity. Its primary outcome was midazolam AUCinf in Cohort 1 across specified periods, with geometric means and geometric coefficients of variation designated as summaries. The record also gives the endpoint's sampling schedule and an analysis-population definition. These details clarify the question and the intended measurement.

What the record does not establish is the numerical answer. Primary endpoint estimates, period contrasts, confidence intervals, and p-values are not reported in the registry record. Consequently, it is not possible from these registry entries to state whether midazolam exposure changed, how large any change was, or how precisely it was estimated. The study's hypothesis that chronic GLP-1 drug administration would minimally affect blood levels is a stated hypothesis, not a result.

The design also limits the kinds of conclusions that can be drawn. The study used open-label fixed sequences and non-randomized allocation. Cohort 1 and Cohort 2 differed in study drug and sequence, so they should not be interpreted as randomized comparison groups. The within-sequence assessments can address the study's pharmacokinetic question, but interpretation depends on analysis details and assumptions that are not reported, including handling of period effects, carryover, and incomplete observations.

The safety listings are likewise descriptive. They show no serious adverse events or deaths in the listed groups and report other adverse-event counts by period. They do not provide a randomized safety contrast or establish causal attribution. The registry record's terminated status does not explain why the study ended, and it does not by itself indicate whether the findings were positive, negative, or incomplete.

In general, a defined endpoint and a completed measurement schedule are not substitutes for estimates and uncertainty intervals. The information available supports understanding the study structure, but not a conclusion about the size or clinical relevance of any pharmacokinetic effect.

13. Why This Trial Matters Statistically

This study illustrates why pharmacokinetic questions require attention to both design and reporting. AUCinf is a continuous exposure measure, and the record specifies that it was summarized with a geometric mean and geometric coefficient of variation. Those choices are meaningful because concentration-derived measures often have multiplicative variation. Yet without the numerical estimates and uncertainty intervals, readers cannot assess the exposure patterns or compare the precision of estimates across periods.

The fixed-sequence design also highlights a statistical distinction between repeated assessment and randomized comparison. Measurements across periods may allow within-participant comparisons, but order, period effects, carryover, and incomplete sequences can matter. The registry record does not describe how these issues were handled analytically. Recognizing that uncertainty is important: the design alone does not reveal the model or guarantee that a particular source of bias was controlled.

Separating cohorts is equally important. PF-07081532 and semaglutide were assessed in different cohorts with different sequences. Treating those cohorts as direct comparative arms would ignore the non-randomized design and the fact that the study questions differ. Clear descriptions of the target comparison and analysis population help prevent overinterpretation.

Finally, the registry illustrates the difference between an endpoint plan and a reported result. It names the primary outcome, sample schedule, and population criteria, yet the primary estimates are not reported in the registry record. Statistical interpretation depends on results and their uncertainty, not only on a study's stated hypothesis or endpoint. This distinction matters when reading pharmacokinetic studies and when deciding what can and cannot be concluded from registry information.

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.

Several trial-specific limitations affect interpretation. The study is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not report whether termination affected completion of the planned sequences or the availability of primary endpoint data.

Although enrollment was 32, the number of participants contributing to the primary AUCinf analysis is not reported in the registry record. The defined analysis population required at least one midazolam dose and at least one calculated pharmacokinetic parameter, but the number meeting those conditions is not given. The safety listings show changing numbers at risk in some later periods, without a full account of withdrawals, sequence completion, or missing observations.

The open-label, non-randomized, fixed-sequence design does not provide a randomized control comparison. The within-cohort sequence comparisons may be vulnerable to period or carryover effects, but period length, washout details, and analytical handling of these effects are not reported. Cohort 1 and Cohort 2 also differ in study drug and sequence, limiting direct comparison between cohorts.

Numerical primary endpoint results, uncertainty estimates, and detailed statistical methods are not reported. Nor are the full multiplicity strategy, missing-data procedures, or interim-analysis details. The number of listed outcome measures makes it especially important to know which analyses were prespecified and how they were interpreted; that information is not reported in the registry record.

Finally, the study population described is limited to otherwise healthy adult female participants with obesity. The registry record does not establish how findings would apply to other populations. Because the primary numerical results are unavailable in the record, these design and population considerations cannot be weighed against an observed effect estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range — NCT05671653.
• Registry record last updated 2025-01-14; status last verified 2025-01.
• Results first posted 2024-12-16.
• 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

NCT05671653 is a Phase 1, open-label, non-randomized study with two parallel cohorts and fixed treatment sequences. It enrolled 32 participants and is listed as terminated. The primary Cohort 1 endpoint was midazolam AUCinf in Periods 1, 4, and 7, summarized using a geometric mean and geometric coefficient of variation. Cohort 1 assessed PF-07081532 alongside midazolam, omeprazole, and an oral contraceptive; Cohort 2 assessed semaglutide alongside midazolam.

The registry record describes the endpoint, sampling schedule, and primary analysis population, but numerical primary results and their uncertainty are not reported. The listed safety groups record no serious adverse events or deaths; other adverse-event counts are reported by period. The reason for termination, detailed statistical plan, missing-data procedures, and complete analysis denominators are not reported in the registry record.