Trial results for a Phase 1 drug-drug interaction study of Orforglipron with quinidine in healthy participants were posted on ClinicalTrials.gov on 2026-05-26. The study investigated the pharmacokinetic profile of Orforglipron when co-administered with quinidine, reporting geometric mean AUC0-inf values of 89.9 nanogram*hour per milliliter and 79.1 nanogram*hour per milliliter for Orforglipron.
Background
The study focused on understanding the pharmacokinetic profile of Orforglipron, specifically how its levels in the bloodstream and elimination time are affected by co-administration with quinidine. This type of drug-drug interaction study is crucial for assessing potential clinical implications when drugs are used concurrently.
Trial design
This Phase 1 drug-drug interaction study (NCT06704763) enrolled 27 healthy participants. The study's purpose was to determine the effect of quinidine on the levels and elimination of Orforglipron when administered orally. Interventions included Orforglipron, midazolam, and quinidine.
Key results
The study reported pharmacokinetic parameters for Orforglipron, midazolam, and 1-hydroxymidazolam when co-administered with quinidine. All measurements were from the 'Midazolam + Orforglipron + Quinidine' group:
- For Orforglipron, the geometric mean Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) was 89.9 nanogram*hour per milliliter (Geometric Coefficient of Variation: 30.4) and 79.1 nanogram*hour per milliliter (Geometric Coefficient of Variation: 30.2).
- The geometric mean Maximum Observed Concentration (Cmax) of Orforglipron was 4.11 nanogram per milliliter (Geometric Coefficient of Variation: 32.2) and 3.06 nanogram per milliliter (Geometric Coefficient of Variation: 39.6).
- For Midazolam, the geometric mean AUC0-inf was 2.06 nanogram*hour per milliliter (Geometric Coefficient of Variation: 41.7) and 2.73 nanogram*hour per milliliter (Geometric Coefficient of Variation: 42.1).
- The geometric mean Cmax of Midazolam was 0.725 nanogram per milliliter (Geometric Coefficient of Variation: 35.2) and 0.999 nanogram per milliliter (Geometric Coefficient of Variation: 49.2).
- For 1-Hydroxymidazolam, the geometric mean AUC0-inf was 0.676 nanogram*hour per milliliter (Geometric Coefficient of Variation: 39.2) and 0.999 nanogram*hour per milliliter (Geometric Coefficient of Variation: 38).
- The geometric mean Cmax of 1-Hydroxymidazolam was 0.224 nanogram per milliliter (Geometric Coefficient of Variation: 39.6) and 0.343 nanogram per milliliter (Geometric Coefficient of Variation: 50.5).
What this means
The posting of these pharmacokinetic results from a Phase 1 drug-drug interaction study provides initial data on how Orforglipron behaves when co-administered with quinidine in healthy individuals. While the detailed analysis of the interaction, such as the specific fold change in exposure, is not explicitly provided in the posted measurements, these geometric mean values for AUC0-inf and Cmax for Orforglipron, midazolam, and 1-hydroxymidazolam are foundational for understanding potential drug interactions. Such data is critical for informing future clinical development, potential dosing adjustments, and labeling considerations for Orforglipron if it is to be used concurrently with drugs like quinidine.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT06704763, titled "A Drug-Drug Interaction Study of Orforglipron (LY3502970) With Quinidine in Healthy Participants", were posted on 2026-05-26 on clinicaltrials.gov.