Clinical trial NCT06186622: A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Obese
Overweight
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-01-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Predose up to 24 hours postdose
measure: PK: AUC [0-∞] of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation
timeFrame: Predose up to 24 hours postdose
measure: PK: AUC [0-∞] of Simvastatin and simvastatin acid after sodium bicarbonate coadministration
timeFrame: Predose up to 24 hours postdose
measure: PK: AUC [0-∞] of Digoxin
timeFrame: Predose up to 120 hours postdose
measure: PK: AUC [0-∞] of Rosuvastatin
timeFrame: Predose up to 72 hours postdose
measure: PK: AUC [0-∞] of Acetaminophen
timeFrame: Predose up to 24 hours postdose
measure: PK: AUC [0-∞] of Midazolam and 1'-hydroxymidazolam
timeFrame: Predose up to 24 hours postdose
measure: PK: Maximum Observed Concentration (Cmax) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation
timeFrame: Predose up to 24 hours postdose
measure: PK: Cmax of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation
timeFrame: Predose up to 24 hours postdose
measure: PK: Cmax of Simvastatin and simvastatin acid after sodium bicarbonate coadministration
timeFrame: Predose up to 24 hours postdose
measure: PK: Cmax of Digoxin
timeFrame: Predose up to 120 hours postdose
measure: PK: Cmax of Rosuvastatin
timeFrame: Predose up to 72 hours postdose
measure: PK: Cmax of Acetaminophen
timeFrame: Predose up to 24 hours postdose
measure: PK: Cmax of Midazolam and 1'-hydroxymidazolam
timeFrame: Predose up to 24 hours postdose
Secondary outcomes:
measure: PK: AUC [0-∞] of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation
timeFrame: Predose up to 24 hours postdose
measure: PK: Cmax of Simvastatin and simvastatin acid after administrating Orforglipron tablet formulation
timeFrame: Predose up to 24 hours postdose
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Fortrea Clinical Research Unit Inc.
state: Florida
city: Dallas
country: United States
facility: Fortrea Clinical Research Unit Inc.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: