A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants

A Drug-Drug Interaction Study to Assess the Effect of Orforglipron on the Pharmacokinetics of Digoxin, Simvastatin, Rosuvastatin, Acetaminophen, and Midazolam in Healthy Overweight and Obese Participants

The main purpose of this study is to determine effect of orforglipron capsule formulation on the amount of digoxin, rosuvastatin, acetaminophen, midazolam, and simvastatin (each given alone and together with orforglipron) that enters the bloodstream and how long it takes the body to eliminate them when administered orally in healthy overweight and obese participants. In addition, the effect of the orforglipron tablet on the amount of simvastatin that enters the bloodstream and how long it takes the body to eliminate it will be evaluated.

The study will also assess the effect of sodium bicarbonate when administered alone with simvastatin versus orforglipron capsule containing sodium bicarbonate administered with simvastatin. The safety and tolerability of orforglipron and information about any side effects experienced will be collected.

Study will be conducted in two parts, with part 1 and 2 lasting up to approximately 23 and 24 weeks each, including the screening period.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Overweight; Obese
• Intervention / Treatment: Drug: Midazolam; Drug: Simvastatin; Drug: Rosuvastatin; Drug: Digoxin; Drug: Orforglipron; Drug: Acetaminophen; Drug: Sodium Bicarbonate

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@Lilly.com

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Active, not recruiting
      • Fortrea Clinical Research Unit Inc.
  • Texas
    • Dallas, Texas, United States, 75247
      • Recruiting
      • Fortrea Clinical Research Unit Inc.
      • Principal Investigator: Abiodun Adefurin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical history and physical examination.
• Have body mass index (BMI) equal to or greater than 27 kilograms per meter squared (kg/m²), inclusive, at screening.
• Have an estimated glomerular filtration rate equal to or greater than 60 milliliters per minute (mL/min).
• Males and females who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
• Have venous access sufficient to allow for blood sampling.

Exclusion Criteria:

• Have any type of diabetes with hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
• Have significant history of or currently have Major Depressive Disorder or psychiatric disorder within the last 2 years.
• Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome.
• Have known clinically significant gastric emptying abnormality.
• Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass)
• Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or any form of thyroid cancer.
• Have an abnormal 12-lead electrocardiogram (ECG) at screening.
• Have significant previous or current history of comorbidities capable of significantly altering the absorption, metabolism, or elimination of drug.
• Participants must not be currently participating in or completed a clinical trial within the last 90 days.
• Have a known allergy or hypersensitivity to midazolam, simvastatin, rosuvastatin, or digoxin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orforglipron (Part 1); Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally.	Drug: Midazolam; Administered orally.; Drug: Simvastatin; Administered orally.; Drug: Rosuvastatin; Administered orally.; Drug: Digoxin; Administered orally.; Drug: Orforglipron; Administered orally.; Other Names: LY3502970; Drug: Acetaminophen; Administered orally.; Drug: Sodium Bicarbonate; Administered orally.
Experimental: Orforglipron (Part 2); Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally.	Drug: Simvastatin; Administered orally.; Drug: Digoxin; Administered orally.; Drug: Orforglipron; Administered orally.; Other Names: LY3502970; Drug: Sodium Bicarbonate; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: AUC [0-∞] of Digoxin		Predose up to 120 hours postdose
PK: AUC [0-∞] of Rosuvastatin		Predose up to 72 hours postdose
PK: AUC [0-∞] of Acetaminophen		Predose up to 24 hours postdose
PK: Cmax of Digoxin		Predose up to 120 hours postdose
PK: Cmax of Rosuvastatin		Predose up to 72 hours postdose
PK: Cmax of Acetaminophen		Predose up to 24 hours postdose
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-∞]) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	PK: AUC [0-∞] of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	Predose up to 24 hours postdose
PK: AUC [0-∞] of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation		Predose up to 24 hours postdose
PK: AUC [0-∞] of Simvastatin and simvastatin acid after sodium bicarbonate coadministration		Predose up to 24 hours postdose
PK: AUC [0-∞] of Midazolam and 1'-hydroxymidazolam		Predose up to 24 hours postdose
PK: Maximum Observed Concentration (Cmax) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	PK: Cmax of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	Predose up to 24 hours postdose
PK: Cmax of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation		Predose up to 24 hours postdose
PK: Cmax of Simvastatin and simvastatin acid after sodium bicarbonate coadministration		Predose up to 24 hours postdose
PK: Cmax of Midazolam and 1'-hydroxymidazolam		Predose up to 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
PK: AUC [0-∞] of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation	Predose up to 24 hours postdose
PK: Cmax of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation	Predose up to 24 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2024
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 16, 2023
• First Submitted That Met QC Criteria: December 16, 2023
• First Posted (Actual): January 2, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Antipyretics; Antimetabolites; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Digoxin; Midazolam; Rosuvastatin Calcium; Acetaminophen; Simvastatin
• Other Study ID Numbers: 18631; J2A-MC-GZPG (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