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

NCT06186622 | Completed Phase 1 FDA Drug

• 2 other identifiers: 18631J2A-MC-GZPG
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Healthy; Obese; Overweight

Outcome Measures

Primary Outcomes (14)

• 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 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: 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 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

• PK: Cmax of Midazolam and 1'-hydroxymidazolam

  Predose up to 24 hours postdose

Secondary Outcomes (2)

• 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

Study Arms (2)

Orforglipron (Part 1)

EXPERIMENTAL

Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally.

Drug: Orforglipron; Drug: Simvastatin; Drug: Digoxin; Drug: Rosuvastatin; Drug: Acetaminophen; Drug: Midazolam; Drug: Sodium Bicarbonate

Orforglipron (Part 2)

EXPERIMENTAL

Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally.

Drug: Orforglipron; Drug: Simvastatin; Drug: Digoxin; Drug: Sodium Bicarbonate

Interventions

Orforglipron DRUG

Administered orally.

Also known as: LY3502970

Orforglipron (Part 1); Orforglipron (Part 2)

Simvastatin DRUG

Administered orally.

Orforglipron (Part 1); Orforglipron (Part 2)

Digoxin DRUG

Administered orally.

Orforglipron (Part 1); Orforglipron (Part 2)

Rosuvastatin DRUG

Administered orally.

Orforglipron (Part 1)

Acetaminophen DRUG

Administered orally.

Orforglipron (Part 1)

Midazolam DRUG

Administered orally.

Orforglipron (Part 1)

Sodium Bicarbonate DRUG

Administered orally.

Orforglipron (Part 1); Orforglipron (Part 2)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

Fortrea Clinical Research Unit Inc.

Daytona Beach, Florida, 32117, United States

Location

Fortrea Clinical Research Unit Inc.

Dallas, Texas, 75247, United States

Location

MeSH Terms

Conditions

Obesity; Overweight

Interventions

orforglipron; Simvastatin; Digoxin; Rosuvastatin Calcium; Acetaminophen; Midazolam; Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Aniline Compounds; Amines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2023
• First Posted: January 2, 2024
• Study Start: January 2, 2024
• Primary Completion: July 10, 2024
• Study Completion: July 10, 2024
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)