The Effect of Imlunestrant on CYP2C8, CYP2C19, CYP2D6, P-gp, and BCRP Activity and the Effect of P-gp Inhibition on Imlunestrant Pharmacokinetics in Healthy Women of Non-childbearing Potential
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 3
- 主要终点
- PK: Cmax of Dextromethorphan (Cohort 2)
研究概览
简要总结
The main purpose of this study is to evaluate the effect of imlunestrant on repaglinide, omeprazole and dextromethorphan, and rosuvastatin and digoxin. The study will also investigate the effect of quinidine on imlunestrant in female healthy participants of non-childbearing potential. The safety and tolerability of imlunestrant will be investigated in female healthy participants of non-childbearing potential. The study will last approximately up to 32 days for each participant excluding the screening period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants who are overtly healthy as determined by medical assessment
- •Body mass index (BMI) within the range 18.0 to 35.0 kilograms per meter squared (kg/m²)
- •Female participants of non childbearing potential.
排除标准
- •Have known allergies to imlunestrant, related compounds or any components of the formulation, repaglinide, omeprazole, dextromethorphan, quinidine, rosuvastatin, or digoxin, as appropriate, or history of significant atopy.
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator
- •Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing
- •Use or intend to use any prescription medications/products within 14 days prior to first dose until completion of the follow-up visit, unless deemed acceptable by the investigator (or designee), including but not limited to medications that inhibit or induce cytochrome P450 (CYP) 2C8, CYP2C19, CYP2D6, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP).
研究组 & 干预措施
Imlunestrant + Repaglinide (Cohort 1)
Participants received:
Day 1: A single oral dose of 0.5 mg repaglinide administered alone. Day 3: A single oral dose of 800 mg imlunestrant, followed approximately 2 hours later by 0.5 mg repaglinide, both administered orally.
干预措施: Imlunestrant (Drug)
Imlunestrant + Repaglinide (Cohort 1)
Participants received:
Day 1: A single oral dose of 0.5 mg repaglinide administered alone. Day 3: A single oral dose of 800 mg imlunestrant, followed approximately 2 hours later by 0.5 mg repaglinide, both administered orally.
干预措施: Repaglinide (Drug)
mlunestrant + Omeprazole & Dextromethorphan (Cohort 2)
Participants received:
Day 1: A single oral dose of 20 mg omeprazole and 30 mg dextromethorphan, administered in the morning.
Day 3: A single oral dose of 800 mg imlunestrant, followed immediately by 20 mg omeprazole and 30 mg dextromethorphan, all administered orally.
干预措施: Imlunestrant (Drug)
mlunestrant + Omeprazole & Dextromethorphan (Cohort 2)
Participants received:
Day 1: A single oral dose of 20 mg omeprazole and 30 mg dextromethorphan, administered in the morning.
Day 3: A single oral dose of 800 mg imlunestrant, followed immediately by 20 mg omeprazole and 30 mg dextromethorphan, all administered orally.
干预措施: Omeprazole (Drug)
mlunestrant + Omeprazole & Dextromethorphan (Cohort 2)
Participants received:
Day 1: A single oral dose of 20 mg omeprazole and 30 mg dextromethorphan, administered in the morning.
Day 3: A single oral dose of 800 mg imlunestrant, followed immediately by 20 mg omeprazole and 30 mg dextromethorphan, all administered orally.
干预措施: Dextromethorphan (Drug)
Imlunestrant + Quinidine (Cohort 3)
Participants received:
Day 1: A single oral dose of 400 mg imlunestrant, administered in the morning. Days 15 to 17 and 19 to 24: Twice-daily oral doses of 200 mg quinidine, administered alone.
Day 18: A single oral dose of 400 mg imlunestrant administered in combination with 200 mg quinidine (quinidine was dosed twice on this day as part of the regular regimen).
干预措施: Imlunestrant (Drug)
Imlunestrant + Quinidine (Cohort 3)
Participants received:
Day 1: A single oral dose of 400 mg imlunestrant, administered in the morning. Days 15 to 17 and 19 to 24: Twice-daily oral doses of 200 mg quinidine, administered alone.
Day 18: A single oral dose of 400 mg imlunestrant administered in combination with 200 mg quinidine (quinidine was dosed twice on this day as part of the regular regimen).
干预措施: Quinidine (Drug)
Imlunestrant + Rosuvastatin & Digoxin (Cohort 4)
Participants received:
Day 1: A single oral dose of 10 mg rosuvastatin and 0.25 mg digoxin, administered in the morning.
Day 10: A single oral dose of 400 mg imlunestrant, administered in combination with 10 mg rosuvastatin and 0.25 mg digoxin, all administered orally.
干预措施: Imlunestrant (Drug)
Imlunestrant + Rosuvastatin & Digoxin (Cohort 4)
Participants received:
Day 1: A single oral dose of 10 mg rosuvastatin and 0.25 mg digoxin, administered in the morning.
Day 10: A single oral dose of 400 mg imlunestrant, administered in combination with 10 mg rosuvastatin and 0.25 mg digoxin, all administered orally.
干预措施: Rosuvastatin (Drug)
Imlunestrant + Rosuvastatin & Digoxin (Cohort 4)
Participants received:
Day 1: A single oral dose of 10 mg rosuvastatin and 0.25 mg digoxin, administered in the morning.
Day 10: A single oral dose of 400 mg imlunestrant, administered in combination with 10 mg rosuvastatin and 0.25 mg digoxin, all administered orally.
干预措施: Digoxin (Drug)
结局指标
主要结局
PK: Cmax of Dextromethorphan (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Dextromethorphan
PK: AUC[0-∞] of Omeprazole (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: AUC\[0-∞\] of Omeprazole
PK: Cmax of Omeprazole (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Omeprazole
PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
5-hydroxyomeprazole is a major metabolite of omeprazole.
PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
5-hydroxyomeprazole is a major metabolite of omeprazole.
PK: AUC[0-∞] of Dextromethorphan (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: AUC\[0-∞\] of Dextromethorphan
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Repaglinide (Cohort 1)
时间窗: Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
PK: AUC\[0-∞\] of Repaglinide
PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1)
时间窗: Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
PK: Cmax of Repaglinide
PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Dextrorphan is a major metabolite of Dextromethorphan.
PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
Dextrorphan is a major metabolite of Dextromethorphan.
PK: AUC[0-∞] of Imlunestrant (Cohort 3)
时间窗: Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
PK: AUC\[0-∞\] of Imlunestrant
PK: Cmax of Imlunestrant (Cohort 3)
时间窗: Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
PK: Cmax of Imlunestrant
PK: AUC[0-∞] of Rosuvastatin (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: AUC\[0-∞\] of Rosuvastatin
PK: Cmax of Rosuvastatin (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: Cmax of Rosuvastatin
PK: AUC[0-∞] of Digoxin (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: AUC\[0-∞\] of Digoxin
PK: Cmax of Digoxin (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: Cmax of Digoxin
次要结局
未报告次要终点