A Phase I Open-Label Study to Determine the Relative Bioavailability of GDC-0134 and to Investigate the Effect of Food and Proton Pump Inhibitor on Pharmacokinetics of GDC-0134 in Healthy Female Subjects of Non-childbearing Potential
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Apparent Half-Life (t1/2) of GDC-0134
研究概览
简要总结
This study will evaluate the pharmacokinetics and safety of GDC-0134 in healthy female volunteers of non-childbearing potential. The first part of the study will compare the bioavailability of a prototype capsule of GDC-0134 relative to an existing GDC-0134 reference capsule (Periods 1 and 2). The second part of the study will assess the effect of GDC-0134-in-applesauce preparation under fasting conditions, the effect of low and high fat foods as well as the effect of elevated stomach pH via pre-treatment with rabeprazole, a proton pump inhibitor (PPI), under fasted and high-fat meal conditions (Periods 3 and 4).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy female participants between 30 and 65 years of age, inclusive;
- •Within body mass index range 18.0 to 35.0 kilograms per square meter (kg/m^2), inclusive;
- •Female participants will be of non-childbearing potential;
- •In good health, determined by no clinically significant findings from medical history, 12-lead echocardiogram (ECG), and vital signs;
- •Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator;
- •Normal ophthalmology assessment.
排除标准
- •Males and females of childbearing potential;
- •Significant history or clinical manifestation of any significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder (as determined by the investigator;
- •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;
- •History of GI bleeding or GI ulcers;
- •Any personal or family history of bleeding disorders, and any personal use of drugs known to affect blood clotting within 30 days of dosing;
- •Any acute or chronic medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study.
研究组 & 干预措施
Treatment Sequence 1: ABC1D1
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Reference capsule GDC-0134 (Drug)
Treatment Sequence 1: ABC1D1
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Prototype capsule GDC-0134 (Drug)
Treatment Sequence 1: ABC1D1
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: rabeprazole (Drug)
Treatment Sequence 2: ABC2D2
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Reference capsule GDC-0134 (Drug)
Treatment Sequence 2: ABC2D2
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Prototype capsule GDC-0134 (Drug)
Treatment Sequence 2: ABC2D2
Single dose of reference capsule GDC-0134 (Treatment A) during Period 1. Single dose of prototype capsule GDC-0134 (Treatment B) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: rabeprazole (Drug)
Treatment Sequence 3: BAC1D1
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Reference capsule GDC-0134 (Drug)
Treatment Sequence 3: BAC1D1
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Prototype capsule GDC-0134 (Drug)
Treatment Sequence 3: BAC1D1
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered as GDC-0134-in-applesauce preparation under fasting conditions (Treatment C1) during Period 3. Single dose of GDC-0134 prototype capsule administered under fasting conditions in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D1) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: rabeprazole (Drug)
Treatment Sequence 4: BAC2D2
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Reference capsule GDC-0134 (Drug)
Treatment Sequence 4: BAC2D2
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: Prototype capsule GDC-0134 (Drug)
Treatment Sequence 4: BAC2D2
Single dose of prototype capsule GDC-0134 (Treatment B) during Period 1. Single dose of reference capsule GDC-0134 (Treatment A) during Period 2. Single dose of GDC-0134 prototype capsule administered after a high-fat meal (Treatment C2) during Period 3. Single dose of GDC-0134 prototype capsule administered after a high-fat meal in combination with 20 mg rabeprazole, and following prior administration of rabeprazole once daily for 3 days (Treatment D2) during Period 4. The washout period between doses will be a minimum of 21 days.
干预措施: rabeprazole (Drug)
结局指标
主要结局
Apparent Half-Life (t1/2) of GDC-0134
时间窗: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
Time to Maximum Concentration (Tmax) of GDC-0134
时间窗: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of GDC-0134
时间窗: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
Area Under the Plasma Concentration-Time Curve up to Time Tau (AUC0-t) of GDC-0134
时间窗: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
The AUC0-t is calculated in a plot of concentration of drug in blood plasma against time and calculated up to the time of the last measurable GDC-0134 concentration.
Maximum Observed Concentration (Cmax) of GDC-0134
时间窗: Periods 1-4: Day 1: pre-dose, post-dose at 0.5 hours (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 16 h, Day 2: post-dose 24 h and 36 h, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Cmax is the maximum observed concentration of drug in blood plasma.
次要结局
- Percentage of Participants with Adverse Events(From baseline until 21 days after the last dose of study drug up to approximately 16 weeks)