NCT01929876已完成1 期
A Phase 1, Open-Label Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Cobimetinib in Healthy Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole
研究概览
简要总结
This open-label, 2-period, fixed sequence, drug interaction study will investigate the effect of co-administration of itraconazole on the pharmacokinetics of cobimetinib in healthy participants. Participants will receive multiple repeating doses of cobimetinib and itraconazole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Healthy adult participants
- •Within body mass index (BMI) range 18.5 to 32 kilogram per meter square (kg/m^2), inclusive
- •Creatine phosphokinase levels below 2.5 times the upper limit of normal (ULN) and if elevated, not clinically significant
- •Liver function tests for aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase below 2 times the ULN; bilirubin below 1.5 times the ULN; and all liver function test elevations not clinically significant
- •In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs
- •Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator
- •Negative test for selected drugs of abuse at screening and at each check-in
- •Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) and negative human immunodeficiency virus (HIV) antibody screens
- •Females non-pregnant or non-lactating
- •Males and females (of child-bearing potential) to use two forms of adequate contraception
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs; except that appendectomy, hernia repair, and/or cholecystectomy will be allowed
- •History of diabetes mellitus and/or elevated fasting glucose at baseline
- •History or presence of an abnormal ECG, which in the Investigator's opinion, is clinically significant
- •History of alcoholism or drug addiction within 1 year prior to study start
- •Use of any tobacco- or nicotine-containing products (within 6 months prior to study start and during the entire study
- •Participation in any other investigational study or biologic agent trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, or exposure to any biological therapy or investigational biological agent within 90 days prior to study entry and during the entire study from study start to study completion, inclusive
研究组 & 干预措施
Cobimetinib + Itraconazole
Experimental
干预措施: Cobimetinib (Drug)
Cobimetinib + Itraconazole
Experimental
干预措施: Itraconazole (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Cobimetinib With and Without Itraconazole
时间窗: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
Maximum observed plasma concentration of cobimetinib with and without itraconazole was assessed using a model independent approach.
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of Cobimetinib With and Without Itraconazole
时间窗: Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4
AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf) of cobimetinib with and without itraconazole, assessed using a model independent approach.
次要结局
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Cobimetinib With and Without Itraconazole(Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Cobimetinib With and Without Itraconazole(Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Plasma Half-Life (t1/2) of Cobimetinib With and Without Itraconazole(Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Apparent Clearance (CL/F) of Cobimetinib With and Without Itraconazole(Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Apparent Volume of Distribution (Vz/F) of Cobimetinib With and Without Itraconazole(Period 1: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192 hours postdose on Day 1; Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Cmax of Itraconazole and Hydroxy-Itraconazole(Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Tmax of Itraconazole and Hydroxy-Itraconazole(Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 192, 240 hours post cobimetinib dose on Day 4)
- Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Itraconazole and Hydroxy-Itraconazole(Period 2: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 12, 24 hours post cobimetinib dose on Day 4)
研究者
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