A Drug-Drug Interaction Study of Orforglipron (LY3502970) With Quinidine in Healthy Participants

A Drug-Drug Interaction, Single-arm, Open-label Study to Assess the Effect of Quinidine on the Pharmacokinetics of Orforglipron in Healthy Participants

The purpose of this study is to determine the effect of quinidine on the levels of orforglipron in the blood stream and how long it takes the body to eliminate it, when administered orally in healthy participants.

The study will last up to approximately 8 weeks including screening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: Orforglipron; Drug: Quinidine

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • ICON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG)

• Have a hemoglobin level of:

  • at least 11.4 grams per deciliter (g/dL) for individuals assigned female at birth (AFAB), and
  • at least 12.5 g/dL for individuals assigned male at birth (AMAB)
• Have a body weight equal to or greater than 45 kilograms (kg), and a body mass index within the range of 18.5 to 35.0 kilogram per square meter (kg/m²) at screening

Exclusion Criteria:

• Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, psychological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting risk when taking orforglipron, midazolam, or quinidine; or interfering with the interpretation of data
• Have a 12 lead electrocardiogram (ECG) abnormality, including known prolongation of QT/QTc interval, significant bradycardia, significant heart blocks or a history of any risk factors for ventricular arrhythmia, heart failure, hypokalemia or hypomagnesemia, or other factors that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have an abnormal blood pressure or pulse rate, deemed to be clinically significant by the investigator
• Have a history of benign ethnic neutropenia
• Have a GI disease or disorder, such as relevant esophageal reflux or gall bladder disease, which could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or impacts gastric emptying, for example gastric bypass surgery or pyloric stenosis, except for appendectomy
• Have a history or presence of pancreatitis, including chronic pancreatitis or idiopathic acute pancreatitis

• Have known allergies to:

  • quinidine
  • midazolam
  • orforglipron
  • related compounds, or
  • any components of the formulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam + Orforglipron + Quinidine; Participants received: Day -1: single dose of 0.2 milligram (mg) midazolam.; Day 1: single dose of 1 mg orforglipron.; Days 5 to 6: 200 mg quinidine twice daily (BID).; Day 7: 200 mg quinidine BID plus a single dose of 0.2 mg midazolam.; Day 8: 200 mg quinidine BID plus a single dose of 1 mg orforglipron.	Drug: Midazolam; Administered orally; Drug: Orforglipron; Administered orally; Other Names: LY3502970; Drug: Quinidine; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Orforglipron	PK: AUC0-inf of Orforglipron.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96 hours post orforglipron dose on days 1, 8
PK: Maximum Observed Concentration (Cmax) of Orforglipron	PK: Cmax of Orforglipron.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96 hours post orforglipron dose on days 1, 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam	PK: AUC0-inf of Midazolam.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7
PK: Maximum Concentration (Cmax) of Midazolam	PK: Cmax of Midazolam.	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of 1-Hydroxymidazolam	PK: AUC0-inf of 1-Hydroxymidazolam (metabolite of Midazolam).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7
PK: Maximum Concentration (Cmax) of 1-Hydroxymidazolam	PK: Cmax of 1-Hydroxymidazolam (metabolite of Midazolam).	Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post midazolam dose on days -1, 7

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Contact Lilly at 1-800-LillyRx (1-800-545-5979), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Benzazepines; Quinolines; Heterocyclic Compounds, Bridged-Ring; Benzodiazepines; Quinuclidines; Cinchona Alkaloids; Midazolam; Quinidine; orforglipron
• Other Study ID Numbers: 27312; J2A-MC-GZPP (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No