A Phase 1, Open-Label Study to Evaluate the Effect of Particle Size, Formulation, and Food on the Pharmacokinetics of GDC-0032 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Maximum Plasma Concentration (Cmax)
研究概览
简要总结
This 4-part study will assess the effect of formulation, food, and active pharmaceutical ingredient (API) lot on the pharmacokinetics of GDC-0032 in healthy volunteers. Part 1 is an open-label, 3-period, 6-sequence study, and Parts 2, 3, and 4 are open-label 2-period crossover studies. Participants will receive single doses of GDC-0032 capsule or tablet formulation, in the fasted or fed state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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 or females of non-childbearing potential, between 18 and 55 years of age, inclusive; females will meet the following criteria: they will be non-pregnant, non-lactating, and either postmenopausal for at least 1 year or surgically sterile for at least 90 days.
- •Body mass index (BMI) 18.5 to 32 kg/m^2, inclusive
- •In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), vital signs and clinical laboratory evaluations
- •Negative test for selected drugs of abuse at Screening (does not include alcohol) and at each Check-in (Day -1; does include alcohol)
- •Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) and negative human immunodeficiency virus (HIV) antibody screens
- •Males will either be sterile or agree to use approved methods of contraception as defined by protocol from Period 1 Check-in (Period 1, Day -1) until 90 days following the last dose of study drug
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 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, except for appendectomy, hernia repair, and/or cholecystectomy
- •History of alcoholism or drug addiction within 1 year prior to Period 1 Check-in (Period 1, Day -1)
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •History of Type 1 or 2 diabetes mellitus and/or elevated fasting glucose (greater than [>] 120 milligrams per deciliter [mg/dL]) at baseline (as confirmed by repeat)
- •History of Gilbert's Syndrome
- •Evidence of malabsorption syndrome or other condition that would interfere with enteral absorption
- •Inability or unwillingness to swallow pills or consume high-fat breakfast
- •Use of any tobacco- or nicotine-containing products within 6 months prior to Period 1 Check-in (Period 1, Day -1) and during the entire study
- •Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer, prior to Period 1 Check-in (Period 1, Day -1) and during the entire study duration
研究组 & 干预措施
Part 1: Food Effect
GDC-0032 will be administered orally over 3-Treatment Period (TP) in 6-sequence as one 3 milligrams (mg) capsule in TP-A after 10 hour fasting from food, one 3 mg Phase III tablet in TP-B after 10 hour fasting from food and one 3 mg Phase III tablet in TP-C following the start of standard Food and Drug Administration (FDA) high-fat breakfast. Washout period o 14 to 20 days will be given between each TP.
干预措施: GDC-0032 Capsule (Drug)
Part 4: Tablet Relative Bioavailibity
GDC-0032 will be administered orally in crossover fashion over 2-TP to 20 participants having 10 hour fasting from food. Participants will receive one 3 mg capsule in TP-A and one 2 mg Phase III tablet in TP-B after 14 to 20 days washout period.
干预措施: GDC-0032 Capsule (Drug)
Part 1: Food Effect
GDC-0032 will be administered orally over 3-Treatment Period (TP) in 6-sequence as one 3 milligrams (mg) capsule in TP-A after 10 hour fasting from food, one 3 mg Phase III tablet in TP-B after 10 hour fasting from food and one 3 mg Phase III tablet in TP-C following the start of standard Food and Drug Administration (FDA) high-fat breakfast. Washout period o 14 to 20 days will be given between each TP.
干预措施: GDC-0032 Phase III Tablet (Drug)
Part 2: Tablet Formulation Comparison
Different formulations of tablets (Tablet A and Tablet B) of GDC-0032 will be administered orally over 2-TP having 10 hour fasting from food. Participants will receive one 3 mg Tablet A in TP-A and one 3 mg Tablet B in TP-B after 14 to 20 days washout period.
干预措施: GDC-0032 Tablet (Drug)
Part 4: Tablet Relative Bioavailibity
GDC-0032 will be administered orally in crossover fashion over 2-TP to 20 participants having 10 hour fasting from food. Participants will receive one 3 mg capsule in TP-A and one 2 mg Phase III tablet in TP-B after 14 to 20 days washout period.
干预措施: GDC-0032 Phase III Tablet (Drug)
Part 3: Capsule API Lot Comparison
Two different lots of GDC-0032 active pharmaceutical ingredient (API) capsule formulation will be administered orally in crossover fashion over 2-TP to 20 participants having 10 hour fasting from food. Participants will receive one 3 mg capsule in TP-A and one 3 mg capsule in TP-B after 14 to 20 days washout period.
干预措施: GDC-0032 Capsule (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax)
时间窗: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour postdose
Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t)
时间窗: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-infinity)
时间窗: Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose
次要结局
- Time to Maximum Plasma Concentration (tmax)(Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose)
- Apparent Terminal Elimination Rate Constant(Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose)
- Apparent Terminal Elimination Constant (t1/2)(Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose)
- Apparent Total Clearance (CL/F)(Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose)
- Apparent Volume of Distribution (Vz/F)(Pre-dose (Hour 0), 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 168, 192 hour post-dose)
- Percentage of Participants With Adverse Events(From Baseline up to approximately 15 weeks)