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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- PK: Cmax of Midazolam and 1'-hydroxymidazolam
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
PK: Cmax of Midazolam and 1'-hydroxymidazolam
时间窗: Predose up to 24 hours postdose
PK: AUC [0-∞] of Rosuvastatin
时间窗: Predose up to 72 hours postdose
PK: AUC [0-∞] of Acetaminophen
时间窗: Predose up to 24 hours postdose
PK: Cmax of Rosuvastatin
时间窗: Predose up to 72 hours postdose
PK: AUC [0-∞] of Simvastatin and simvastatin acid after sodium bicarbonate coadministration
时间窗: Predose up to 24 hours postdose
PK: AUC [0-∞] of Digoxin
时间窗: Predose up to 120 hours postdose
PK: AUC [0-∞] of Midazolam and 1'-hydroxymidazolam
时间窗: Predose up to 24 hours postdose
PK: Cmax of Simvastatin and simvastatin acid following staggered administration of Orforglipron capsule formulation
时间窗: 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
时间窗: 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
时间窗: Predose up to 24 hours postdose
PK: Maximum Observed Concentration (Cmax) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation
时间窗: Predose up to 24 hours postdose
PK: Cmax of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation
PK: Cmax of Simvastatin and simvastatin acid after sodium bicarbonate coadministration
时间窗: Predose up to 24 hours postdose
PK: Cmax of Digoxin
时间窗: Predose up to 120 hours postdose
PK: Cmax of Acetaminophen
时间窗: Predose up to 24 hours postdose
次要结局
- 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)