A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants
Phase 1
Completed
- Conditions
- HealthyObeseOverweight
- Interventions
- Registration Number
- NCT06186622
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Orforglipron (Part 1) Orforglipron Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 2) Orforglipron Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Digoxin Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Simvastatin Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Midazolam Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Rosuvastatin Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Acetaminophen Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 1) Sodium Bicarbonate Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally. Orforglipron (Part 2) Simvastatin Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally. Orforglipron (Part 2) Digoxin Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally. Orforglipron (Part 2) Sodium Bicarbonate Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally.
- Primary Outcome Measures
Name Time Method PK: Cmax of Simvastatin and simvastatin acid after sodium bicarbonate coadministration Predose up to 24 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 Rosuvastatin Predose up to 72 hours postdose PK: Cmax of Midazolam and 1'-hydroxymidazolam 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 Midazolam and 1'-hydroxymidazolam 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 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 Predose up to 24 hours postdose PK: AUC \[0-∞\] of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation
PK: AUC [0-∞] of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation Predose up to 24 hours postdose PK: Maximum Observed Concentration (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 simultaneous administration of Orforglipron capsule formulation
PK: Cmax of Digoxin Predose up to 120 hours postdose PK: Cmax of Acetaminophen Predose up to 24 hours postdose
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Fortrea Clinical Research Unit Inc.
🇺🇸Dallas, Texas, United States