A Drug-Drug Interaction (DDI) Study of Orforglipron With Carbamazepine in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Drug-Drug Interaction (DDI) Study of Orforglipron With Carbamazepine in Healthy Participants (NCT06370728), a na phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Orforglipron.

2. Clinical Question

3. Trial Design

This completed Phase 1 study enrolled 30 healthy participants. The registry record identifies its model as single group and its allocation as NA; it does not describe a randomized, parallel-group comparison. The study title and summary identify the purpose as assessing the effect of carbamazepine on orforglipron pharmacokinetics, alongside evaluation of safety and tolerability.

The described sequence began with 1 mg orforglipron alone on Day 1. Carbamazepine was then administered twice daily, with 100 mg doses on Days 6 to 8, 200 mg doses on Days 9 to 11, and 300 mg doses on Days 12 to 14. The adverse-event group descriptions separately identify a combination period on Day 15, a carbamazepine-alone period covering Days 6 to 18 except Day 15 and Days 19 to 35, and an orforglipron-alone period covering Days 1 to 5. These labels describe periods, not randomized treatment groups.

The primary pharmacokinetic endpoint was assessed using samples collected on Day 1 and Day 15 at predose and the listed post-dose times through 72 hours. The registry record says participation may last up to approximately 77 days for each participant. The study start date was 2024-05-06, primary completion was 2024-07-23, and its status is completed.

The record does not report a control group, masking, or an allocation procedure; masking is listed as none. It also does not report a protocol rationale for the dosing sequence or a sample-size justification. The listed enrollment should therefore be read as the study’s total enrollment, not as a count for each period or treatment condition.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of orforglipron and had evaluable PK data on the respective dosing days for this outcome 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.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Orforglipron, measured over Day 1 (Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours post-dose); Day 15 (Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours post-dose).

The primary endpoint is orforglipron’s area under the concentration-versus-time curve from time zero to infinity, abbreviated AUC (0-∞). It is reported as a geometric mean, with geometric coefficient of variation as the stated measure of dispersion. The unit is nanograms*hours per milliliter(ng*h/mL).

In general, an area under a concentration-time curve represents drug exposure over time: it combines the measured concentrations across the observation period and estimates exposure through infinity. This is useful in a pharmacokinetic interaction study because the study question concerns whether carbamazepine changes the amount of orforglipron in the bloodstream. AUC is one way to characterize that amount over time, while the study summary also refers to how long the body takes to get rid of orforglipron.

The endpoint is based on pharmacokinetic measurements on Day 1 and Day 15. The listed sampling schedule on each day includes predose and post-dose measurements at 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours. The analysis population is described as enrolled participants who received at least one orforglipron dose and had evaluable pharmacokinetic data on the relevant dosing days.

The registry record does not report geometric-mean AUC values, their variability, a contrast between dosing days, or an uncertainty interval. The endpoint definition alone therefore explains what was intended to be measured, but not the size or precision of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives the primary endpoint’s summary type and dispersion measure, but does not report a statistical analysis plan or numerical results. The methods below explain the statistical ideas relevant to the recorded endpoint in general; they should not be read as a description of unreported analyses from this study.

What does AUC measure?

In general, area under the concentration-versus-time curve summarizes exposure across the period of observation. Rather than describing a concentration at only one sampling time, AUC uses information across multiple measurements. AUC (0-∞) refers to exposure from time zero through an extrapolated infinite time horizon. The registry lists predose and post-dose pharmacokinetic sampling on Day 1 and Day 15, with measurements extending to 72 hours post-dose. It does not report the calculation details or the resulting AUC estimates.

Using an AUC endpoint is relevant to a pharmacokinetic interaction question because a change in overall exposure can be assessed through a summary of concentration over time. The endpoint does not, by itself, describe every feature of the concentration profile. For example, the same overall exposure summary does not automatically communicate the concentration at a particular time or the time to peak concentration. The record’s stated primary endpoint is specifically AUC (0-∞); other endpoint details and numerical results are not reported in the registry record.

Why use a geometric mean?

In general, a geometric mean summarizes positive values on a multiplicative scale. It is often useful when measurements are right-skewed or when relative changes are more meaningful than absolute changes. This general rationale does not establish why the investigators selected this summary for this study; that rationale is not reported in the registry record. The record names the geometric mean as the primary endpoint parameter and geometric coefficient of variation as the dispersion measure.

A geometric coefficient of variation is a way to describe relative variability for measurements summarized geometrically. In general, dispersion matters because individual participants may have different pharmacokinetic measurements even when they follow the same dosing sequence. A summary mean without a measure of spread can conceal that variability. The registry record does not give the observed coefficient of variation, its calculation method, or participant-level values.

What would a comparison need to show?

To interpret the interaction question, a reader would need the relevant AUC estimates for the dosing conditions, a clearly specified contrast, and an uncertainty measure. In general, a confidence interval communicates the range of values compatible with the data under the statistical method used. A narrow interval indicates greater precision than a wide interval, while the interval’s location helps describe the estimated effect. No confidence interval or contrast is reported in the registry record, so neither direction nor precision can be assessed.

A statistical test, when used, evaluates data relative to a specified null hypothesis and assumptions. A p-value does not measure the size or importance of an effect. The registry record does not report a p-value, test statistic, null hypothesis, or testing procedure. It is therefore not possible to say whether a formal test was conducted or what its result was.

What does the study structure imply?

The registry identifies a single-group model, with no allocation listed and no masking. It describes an ordered sequence that includes orforglipron alone, carbamazepine dosing, and a combination period. In general, repeated measurements within participants can reduce some between-person variability when comparing conditions, but they also require attention to order, time, carryover, and missing observations. The record does not report how these issues were handled or whether they were relevant to the analysis.

Because the record does not describe a randomized parallel-group comparison, the periods should not be interpreted as independent randomized arms. The registry record does not report a model for accounting for the sequence or within-participant measurements. It also does not report whether any baseline adjustment, transformation, or sensitivity analysis was used.

How should planning illustrations be understood?

In general, power calculations are planning tools that relate a target effect, variability, significance level, allocation, and sample size to the chance of detecting an effect under specified assumptions. They do not describe what happened in the observed data. The registry record does not report the study’s own sample-size justification or statistical design assumptions. A separate planning illustration described for this analysis uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with target effects expressed as fractions of an observed effect. Those assumptions do not match the recorded single-group design and should not be read as the trial’s design or as observed power. The record does not report numerical endpoint results from which to judge an observed effect.

More broadly, the statistical methods that would determine how the endpoint was estimated and compared—including handling of missing pharmacokinetic measurements, analysis populations, multiplicity, and uncertainty—are not reported in the registry record. The endpoint definition provides useful context, but it is not a substitute for those methods or the numerical findings.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, but it does not provide the details of all three in the information recorded for this analysis. The primary endpoint is AUC (0-∞) of orforglipron. The record does not report how multiple endpoints, time points, or statistical tests were prioritized or whether any adjustment for multiplicity was planned. Without that information, the handling of the possibility of false-positive findings across multiple analyses cannot be assessed.

The endpoint population is described as participants who were enrolled, received at least one dose of orforglipron, and had evaluable pharmacokinetic data on the relevant dosing days. This definition indicates that evaluable data were required for inclusion in the endpoint analysis. The record does not report how many participants met those criteria, whether any data were missing, why data might have been unavailable, or how missing observations were handled. It also does not report whether participants were excluded from an analysis or whether any imputation or sensitivity analysis was used.

The registry lists no analyses, and numerical endpoint results are not reported in the registry record. The statistical analysis plan, including any prespecified analysis population beyond the endpoint description, is not reported. Consequently, it is not possible to determine whether analyses followed a prespecified plan or whether any analysis decisions were made after data were reviewed.

These omissions do not establish that data were missing or that multiplicity adjustments were needed. They mean that the registry record does not provide the information needed to evaluate those issues. The stated endpoint population and the existence of three outcome measures provide context, but they do not explain the analysis procedures.

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 record lists serious adverse events by study period. There were 30 participants at risk in the orforglipron-alone period and 0 with a serious adverse event. In the carbamazepine-alone period, 29 were at risk and 0 had a serious adverse event. In the orforglipron-plus-carbamazepine period, 28 were at risk and 0 had a serious adverse event. Deaths were 0 in each listed period.

These are period-specific counts, not results from randomized, independent treatment groups. The number at risk differs across the periods, and the record does not provide participant-level information or explain the reasons for those differences. Counts should therefore be read descriptively rather than as a controlled comparison of safety between treatments.

The record also lists other adverse events, which are distinct from serious adverse events: 4 in the orforglipron-alone period, 12 in the carbamazepine-alone period, and 2 in the combination period. Those counts do not change the serious-event figures. The registry record does not provide details of the event terms or a statistical comparison. Zero serious events in the listed periods describes what was recorded; it does not establish that serious events are impossible or that the periods have equivalent safety.

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

This study addresses a focused pharmacokinetic question: whether carbamazepine affects orforglipron exposure in healthy participants. Its primary endpoint, AUC (0-∞), is a measure of overall drug exposure across time. The registry record identifies the study as completed and describes a dosing sequence that includes orforglipron alone and a period in which orforglipron and carbamazepine were combined.

The registry record does not report numerical AUC estimates, an effect estimate comparing the relevant periods, or an uncertainty interval. It therefore does not show the observed direction or size of a pharmacokinetic difference. Without those results, the statistical precision of the estimated interaction cannot be evaluated. A completed status and a defined endpoint are not substitutes for reported findings.

The record also does not establish clinical consequences. This is a Phase 1 study in healthy participants, and the primary endpoint is pharmacokinetic rather than a patient-centered clinical outcome. The study summary includes safety and tolerability as evaluation aims, but the registry record does not report detailed safety analyses beyond the event counts by period. No conclusion about clinical benefit, harm, or treatment decisions follows from the endpoint definition alone.

The design is recorded as single group, with allocation NA and no masking. Its described periods are not randomized, like-for-like comparator arms. Any interpretation of differences between periods would need to account for the study sequence and the methods used to analyze repeated pharmacokinetic observations. Those methods and results are not reported in the registry record.

In short, the record establishes what the study set out to measure and how the dosing periods were described. It does not provide the primary numerical result needed to determine whether carbamazepine changed orforglipron AUC, or how precisely such a change was estimated. That distinction separates the study question from the evidence available in the registry record.

13. Why This Trial Matters Statistically

Drug–drug interaction studies raise statistical questions that differ from those in a conventional parallel-group trial. The focus is on whether exposure to one drug changes in the presence of another, and the outcome is commonly a pharmacokinetic measure rather than a clinical event. Here, the registry names AUC (0-∞) of orforglipron as the primary endpoint and describes dosing periods involving orforglipron alone, carbamazepine alone, and the combination.

The study structure matters for interpretation. A single-group sequence is not equivalent to a randomized comparison between separate groups. Period comparisons may involve repeated observations within participants, so the analysis approach and treatment of period order are important. The registry record does not report those methods. Recognizing that limitation prevents the period labels from being mistaken for independent randomized arms.

The endpoint’s summary scale also matters. A geometric mean and geometric coefficient of variation describe the data differently from an arithmetic mean and standard deviation. In general, geometric summaries are suited to positive measurements where relative variation is of interest. Readers need both the effect estimate and its uncertainty to understand how much the exposure may have changed and how precisely it was estimated. Neither is reported in the registry record.

This record is therefore statistically informative about the question, endpoint, sampling schedule, study sequence, and endpoint population, while leaving the central numerical result unavailable. It illustrates why study registration details and outcome results serve different purposes: a clear endpoint definition cannot answer an empirical question without the corresponding estimates and analysis methods.

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 central limitation is that numerical pharmacokinetic results are not reported in the registry record. Although the primary endpoint and its measurement schedule are identified, no AUC estimates, contrast, confidence interval, or p-value is available. The effect’s direction, magnitude, and precision therefore cannot be assessed from this record.

The registry record lists a single-group model and allocation NA. The described periods are sequential rather than separate randomized comparison groups. The record does not report the statistical model used to compare periods or how the analysis addressed within-participant measurements, sequence, or period effects. No masking was used, according to the record.

The endpoint population requires receipt of at least one orforglipron dose and evaluable pharmacokinetic data on the relevant days, but the number of participants meeting this definition is not reported. The record also does not report whether data were missing, how missing measurements were handled, or whether sensitivity analyses were performed. The statistical analysis plan and sample-size justification are not reported.

The study enrolled healthy participants and was designed around pharmacokinetics and safety and tolerability. The registry record does not describe a clinical outcome assessment. Its findings, even if reported elsewhere, would need to be interpreted within that study context rather than assumed to answer questions about outcomes in other populations. The adverse-event information is limited to period-level counts, with no detailed event terms or comparative analysis reported.

Finally, the record lists three outcome measures but provides no analyses. It does not report multiplicity procedures or whether analyses were prespecified. These gaps limit evaluation of the statistical evidence, not merely the interpretation of a particular estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Drug-Drug Interaction (DDI) Study of Orforglipron With Carbamazepine in Healthy Participants — NCT06370728.
• Registry record last updated 2026-07-17; status last verified 2026-06.
• Results first posted 2026-07-17.
• 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

NCT06370728 is a completed Phase 1 study titled “A Drug-Drug Interaction (DDI) Study of Orforglipron With Carbamazepine in Healthy Participants.” It enrolled 30 healthy participants and is recorded as a single-group study with allocation NA and no masking. The study began on 2024-05-06, reached primary completion on 2024-07-23, and is listed as completed.

The primary endpoint was orforglipron AUC (0-∞), summarized as a geometric mean with geometric coefficient of variation. The described sequence included orforglipron alone, carbamazepine dosing, and a combination period. The registry record does not report numerical primary endpoint results or analyses. Serious adverse events and deaths were recorded as 0 in each listed period; these period-specific counts are descriptive.