Evaluation of the Effect of Food, Omeprazole, Itraconazole, and Carbamazepine on the Pharmacokinetics of LY3484356 in Healthy Females of Non-Child-Bearing Potential
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 2
- 主要终点
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3484356 (Cohort 1)
研究概览
简要总结
The main purpose of this study is to evaluate the amount of LY3484356 that is found in the blood stream and how long the body takes to get rid of it when given with and without food. Participants are healthy females of non-childbearing potential. The study will also evaluate the tolerability and safety of LY3484356 by collecting the information about any side effects that may occur. The participant's involvement with the study will last approximately 27 days, not including screening.
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. This includes females who are not pregnant, non-lactating and either: Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy or bilateral salpingectomy, bilateral tubal ligation, or bilateral tubal occlusion), or alternate medical cause/congenital anomaly (for example, Müllerian agenesis) or postmenopausal
排除标准
- •Have a history or presence of cardiovascular (eg, symptomatic bradycardia with resting heart rate of <60 beats per minute), respiratory, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
- •Show evidence of hepatitis B, evidence of hepatitis C and/or have evidence of human immunodeficiency virus (HIV) infection
- •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 medications that inhibit or induce CYP3A4 within 14 days prior to dosing until completion of the follow-up visit
- •Smoke more than 10 cigarettes or use the equivalent tobacco, smoking-cessation products, nicotine-containing products, or e cigarettes (nicotine and non nicotine) per day
研究组 & 干预措施
Cohort 1 Sequence 1: 400 mg LY3484356 Fasted/ 400 mg LY3484356 Fed
Participants were randomized (1:1) to 1 of 2 treatment sequences; LY3484356 administered as single doses orally with (fed) or without food (fasted) as below:
Period 1: Single dose of 400 mg LY3484356 in the fasted state. Period 2: Single dose of 400 mg LY3484356 in the fed state. There was a washout period of 4 days between doses of LY3484356
干预措施: LY3484356 (Drug)
Cohort 1 Sequence 2: 400 mg LY3484356 Fed/ 400 mg LY3484356 Fasted
Participants were randomized (1:1) to 1 of 2 treatment sequences; LY3484356 administered as single doses orally with (fed) or without food (fasted) as below:
Period 1: Single dose of 400 mg LY3484356 in the fed state. Period 2: Single dose of 400 mg LY3484356 in the fasted state. There was a washout period of 4 days between doses of LY3484356.
干预措施: LY3484356 (Drug)
Cohort 2: LY3484356 + Omeprazole
Participants received single dose of LY3484356 and a single dose of omeprazole alone and in combination administered orally as below:
Day 1: 400 mg LY3484356 alone Days 5 to 8: 40 mg omeprazole alone once daily Day 9: 400 mg LY3484356 + 40 mg omeprazole once There was a washout period of 8 days between doses of LY3484356.
干预措施: LY3484356 (Drug)
Cohort 2: LY3484356 + Omeprazole
Participants received single dose of LY3484356 and a single dose of omeprazole alone and in combination administered orally as below:
Day 1: 400 mg LY3484356 alone Days 5 to 8: 40 mg omeprazole alone once daily Day 9: 400 mg LY3484356 + 40 mg omeprazole once There was a washout period of 8 days between doses of LY3484356.
干预措施: Omeprazole (Drug)
Cohort 3: LY3484356 + Itraconazole
Participants received single dose of LY3484356 and a single dose of Itraconazole alone and in combination administered orally as below:
Day 1: 200 mg LY3484356 alone Days 5 to 9: 200 mg itraconazole alone (twice on Day 5 [dose separated by approximately 12 hours], then once daily on Days 6 through 9) Day 10: 200 mg LY3484356 + 200 mg itraconazole once (coadministered with the morning dose) Days 11 to 16: 200 mg itraconazole alone once daily. There was a washout period of 9 days between doses of LY3484356.
干预措施: LY3484356 (Drug)
Cohort 3: LY3484356 + Itraconazole
Participants received single dose of LY3484356 and a single dose of Itraconazole alone and in combination administered orally as below:
Day 1: 200 mg LY3484356 alone Days 5 to 9: 200 mg itraconazole alone (twice on Day 5 [dose separated by approximately 12 hours], then once daily on Days 6 through 9) Day 10: 200 mg LY3484356 + 200 mg itraconazole once (coadministered with the morning dose) Days 11 to 16: 200 mg itraconazole alone once daily. There was a washout period of 9 days between doses of LY3484356.
干预措施: Itraconazole (Drug)
Cohort 4: LY3484356 + Carbamazepine
Participants received single dose of LY3484356 and a single dose of carbamazepine alone and in combination administered orally as below:
Day 1: 400 mg LY3484356 alone Days 6 to 8: 100 mg carbamazepine BID alone Days 9 to 11: 200 mg carbamazepine BID alone Days 12 to 17: 300 mg carbamazepine BID alone Day 18: 300 mg carbamazepine BID + 400 mg LY3484356 (coadministered with morning dose) Days 19 to 22: 300 mg carbamazepine BID alone Day 23: 300 mg carbamazepine alone (morning dose only). There was a washout period of 17 days between doses of LY3484356.
干预措施: LY3484356 (Drug)
Cohort 4: LY3484356 + Carbamazepine
Participants received single dose of LY3484356 and a single dose of carbamazepine alone and in combination administered orally as below:
Day 1: 400 mg LY3484356 alone Days 6 to 8: 100 mg carbamazepine BID alone Days 9 to 11: 200 mg carbamazepine BID alone Days 12 to 17: 300 mg carbamazepine BID alone Day 18: 300 mg carbamazepine BID + 400 mg LY3484356 (coadministered with morning dose) Days 19 to 22: 300 mg carbamazepine BID alone Day 23: 300 mg carbamazepine alone (morning dose only). There was a washout period of 17 days between doses of LY3484356.
干预措施: Carbamazepine (Drug)
Cohort 5: Carbamazepine + Midazolam
Participants received single dose of Carbamazepine and a single dose of midazolam alone and in combination administered orally as below:
Day 1: 1.2 mg midazolam alone Days 2 to 4: 100 mg carbamazepine BID alone Days 5 to 7: 200 mg carbamazepine BID alone Days 8 to 10: 300 mg carbamazepine BID alone Day 11: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose) Days 12 to 13: 300 mg carbamazepine BID alone Day 14: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose).
干预措施: Carbamazepine (Drug)
Cohort 5: Carbamazepine + Midazolam
Participants received single dose of Carbamazepine and a single dose of midazolam alone and in combination administered orally as below:
Day 1: 1.2 mg midazolam alone Days 2 to 4: 100 mg carbamazepine BID alone Days 5 to 7: 200 mg carbamazepine BID alone Days 8 to 10: 300 mg carbamazepine BID alone Day 11: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose) Days 12 to 13: 300 mg carbamazepine BID alone Day 14: 300 mg carbamazepine BID + 1.2 mg midazolam (coadministered with morning dose).
干预措施: Midazolam (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3484356 (Cohort 1)
时间窗: Period 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours (h) postdose; Period 2: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 and 96 h postdose
PK: AUC\[0-∞\] of LY3484356
PK: AUC[0-∞] of LY3484356 (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 9: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
PK: AUC\[0-∞\] of LY3484356
PK: AUC[0-∞] of LY3484356 (Cohort 3)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 10: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
PK: AUC\[0-∞\] of LY3484356
PK: AUC[0-∞] of LY3484356 (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 18: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
AUC\[0-∞\] of LY3484356
PK: Time of Maximum Observed Concentration (Tmax) of LY3484356 (Cohort 1)
时间窗: Period 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 h postdose; Period 2: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 and 96 h postdose
PK: Tmax of LY3484356
PK: Tmax of LY3484356 (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 9: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
PK: Tmax of LY3484356
PK: Tmax of LY3484356 (Cohort 3)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 10: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
PK: Tmax of LY3484356
PK: Tmax of LY3484356 (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 18: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
Tmax of LY3484356
PK: Maximum Observed Concentration (Cmax) of LY3484356 (Cohort 1)
时间窗: Period 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 h postdose; Period 2: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 and 96 h postdose
Cmax of LY3484356
PK: Cmax of LY3484356 (Cohort 2)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 9: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
Cmax of LY3484356
PK: Cmax of LY3484356 (Cohort 3)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 10: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
Cmax of LY3484356
PK: Cmax of LY3484356 (Cohort 4)
时间窗: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose; Day 18: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h postdose
Cmax of LY3484356
次要结局
未报告次要终点