A Phase 1, Open Label, Two-part, Fixed-sequence Drug Interaction Study to Investigate the Effect of Strong CYP3A4 Inhibitor (Itraconazole) and CYP3A4 Inducer (Rifampin) on the Pharmacokinetics of LOXO 305 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305
研究概览
简要总结
The main purpose of this study is to learn about how itraconazole and rifampin affect LOXO-305 in healthy participants. Participation could last about 8 weeks.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females of non-childbearing potential.
- •Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²).
- •Participants will be in good general health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), or clinical laboratory tests, as determined by the Investigator (or designee).
- •Able to comply with all study procedures, including the 19-night stay for those participating in Part 1 or 24-night stay for those participating in Part 2 at the Clinical Research Unit and follow-up phone call.
排除标准
- •History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor:
- •liver disease
- •pancreatitis
- •peptic ulcer disease
- •intestinal malabsorption
- •gastric reduction surgery
- •history or presence of clinically significant cardiovascular disease.
- •Participants with out-of-range, at-rest vital signs.
- •Abnormal laboratory values determined to be clinically significant by the Investigator (or designee).
- •Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination.
- •Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to the first dose administration (Day 1).
- •Use or intention to use any prescription or over-the-counter medications within 14 days prior to the first dose administration (Day 1) and through end of trial.
- •History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk.
- •Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening.
- •Receipt of blood products within 2 months prior to Check-in (Day -1).
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the Investigator), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).
研究组 & 干预措施
Part 1 (LOXO-305/Itraconazole)
- Day 1: a single oral dose of 200 milligrams (mg) LOXO-305 was administered.
- Day 8: oral doses of 200 mg itraconazole was administered twice daily.
- Days 9 to 18: single oral dose of 200 mg itraconazole was administered once daily, and on Day 12 it was co-administered with a single oral dose of 200 mg LOXO-305.
干预措施: LOXO-305 (Drug)
Part 1 (LOXO-305/Itraconazole)
- Day 1: a single oral dose of 200 milligrams (mg) LOXO-305 was administered.
- Day 8: oral doses of 200 mg itraconazole was administered twice daily.
- Days 9 to 18: single oral dose of 200 mg itraconazole was administered once daily, and on Day 12 it was co-administered with a single oral dose of 200 mg LOXO-305.
干预措施: Itraconazole (Drug)
Part 2 (LOXO 305/Rifampin)
- Day 1: a single oral dose of 200 mg LOXO-305 was administered.
- Days 8 to 23: oral dose of 600 mg rifampin was administered once daily, and on Days 8 & 17, it was co-administered with a single oral dose of 200 mg LOXO-305.
干预措施: LOXO-305 (Drug)
Part 2 (LOXO 305/Rifampin)
- Day 1: a single oral dose of 200 mg LOXO-305 was administered.
- Days 8 to 23: oral dose of 600 mg rifampin was administered once daily, and on Days 8 & 17, it was co-administered with a single oral dose of 200 mg LOXO-305.
干预措施: Rifampin (Drug)
结局指标
主要结局
Part 1: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LOXO-305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
Cmax of LOXO-305
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
PK: AUC0-t of LOXO 305
Part 1: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 12
AUC0-inf of LOXO-305
Part 2: PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
Cmax of LOXO-305
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of LOXO 305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17; Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on day 8
PK: AUC0-t of LOXO 305
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of LOXO-305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on days 1 and 17
AUC0-inf of LOXO-305
Part 2: PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of LOXO-305
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on days 1 and 8
AUC0-24 of LOXO-305
次要结局
未报告次要终点