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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06186622
• Other study ID #: 18631
• Secondary ID: J2A-MC-GZPG
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 2, 2024
• Est. completion date: June 17, 2024

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: June 17, 2024
• Est. primary completion date: June 17, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Obese
• Overweight

Intervention

Drug:
• Orforglipron
Administered orally.
• Simvastatin
Administered orally.
• Digoxin
Administered orally.
• Rosuvastatin
Administered orally.
• Acetaminophen
Administered orally.
• Midazolam
Administered orally.
• Sodium Bicarbonate
Administered orally.

Locations

Country	Name	City	State
United States	Fortrea Clinical Research Unit Inc.	Dallas	Texas
United States	Fortrea Clinical Research Unit Inc.	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-8]) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	PK: AUC [0-8] of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation	Predose up to 24 hours postdose
Primary	PK: AUC [0-8] of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation		Predose up to 24 hours postdose
Primary	PK: AUC [0-8] of Simvastatin and simvastatin acid after sodium bicarbonate coadministration		Predose up to 24 hours postdose
Primary	PK: AUC [0-8] of Digoxin		Predose up to 120 hours postdose
Primary	PK: AUC [0-8] of Rosuvastatin		Predose up to 72 hours postdose
Primary	PK: AUC [0-8] of Acetaminophen		Predose up to 24 hours postdose
Primary	PK: AUC [0-8] of Midazolam and 1'-hydroxymidazolam		Predose up to 24 hours postdose
Primary	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
Primary	PK: Cmax of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation		Predose up to 24 hours postdose
Primary	PK: Cmax of Simvastatin and simvastatin acid after sodium bicarbonate coadministration		Predose up to 24 hours postdose
Primary	PK: Cmax of Digoxin		Predose up to 120 hours postdose
Primary	PK: Cmax of Rosuvastatin		Predose up to 72 hours postdose
Primary	PK: Cmax of Acetaminophen		Predose up to 24 hours postdose
Primary	PK: Cmax of Midazolam and 1'-hydroxymidazolam		Predose up to 24 hours postdose
Secondary	PK: AUC [0-8] of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation		Predose up to 24 hours postdose
Secondary	PK: Cmax of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation		Predose up to 24 hours postdose