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

Lilly

Status and phase: Completed; Phase 1

Conditions: Overweight; Obese; Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06186622

18631

J2A-MC-GZPG (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Orforglipron (Part 1)

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: Rosuvastatin

Drug: Digoxin

Drug: Acetaminophen

Drug: Simvastatin

Drug: Sodium Bicarbonate

Drug: Orforglipron

Orforglipron (Part 2)

Experimental group

Description:

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

Treatment:

Drug: Digoxin

Drug: Simvastatin

Drug: Sodium Bicarbonate

Drug: Orforglipron

Sponsor of this trial

Lead Sponsor

Lilly