A Phase I, Randomized, Single and Multiple Ascending Dose, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, and Pharmacokinetics of GDC-0310 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of single and multiple orally ascending doses of GDC-0310 administered in healthy participants as 4 parts including Part 1- a single dose (SD) part using a powder-in-capsule (PIC) formulation, Part 2- a multiple dose (MD) part using a PIC formulation, Part 3- a SD part using a solution formulation, and Part 4- a MD part using a solution formulation. Effects of food on pharmacokinetics (PK) will also be explored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female participants of non-childbearing potential must meet the criteria defined in the protocol
- •Body mass index within the range of 18.0 to 30.0 kilograms per meter square (kg/m^2), inclusive, and a minimum weight of 50.0 kg
排除标准
- •Have a clinically significant medical condition (e.g., hypertension; diabetes; impaired cardiac, renal or hepatic function; hyperthyroidism or hypothyroidism; neurological disorder; pain condition; hematologic disorder; psychiatric disorders requiring chronic medication) including any medical condition requiring treatment with medication (other than study drugs and medications specifically allowed by this protocol) during participation in the study
- •Evidence of any hepatic impairment including any abnormal levels (i.e., greater than [>] 1 × the upper limit of normal) of alkaline phosphatase, gamma glutamyl transpeptidase, alanine transaminase, aspartate aminotransferase or bilirubin
- •Evidence of clinically significant renal impairment defined as >1.3 × upper limit of normal creatinine
- •History or presence of alcoholism or alcohol or substance abuse (not including nicotine or caffeine) within the previous 2 years or routinely consume 2 or more alcohol-containing beverages per day or more than 10 units of alcohol per week (1 unit =150 milliliter (mL) of wine, 360 mL of beer, or 45 mL of 40 percent (%) alcohol)
- •Have a positive urine drug test at screening or check-in or any other point during the study
- •Are habituated to analgesic drugs (i.e., routine use of oral analgesics 5 or more times per week) or have a history of chronic pain requiring opiate use
- •Have used tobacco or nicotine-containing products within 3 months before study drug administration
- •Have clinically significant abnormal laboratory values as determined by the principal investigator
- •Have used any prescription or over-the-counter medication or supplement within 14 days or 5 times the elimination half-life (whichever is longer) before administration of study drug and until the end of their participation in the study
- •History of seizures, including in first degree relatives
- •History of heritable myopathy, weakness, or paralysis, including in first degree relatives indicative of familial periodic paralysis
- •Current treatment with medications that are well known to prolong the QT interval
研究组 & 干预措施
High-Fat Meal SD Cohort: PIC (Part 1)
Participants will receive GDC-0310 single ascending dose based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a high-fat meal after a 8-hour/overnight fast using PIC on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.
干预措施: GDC-0310 (Drug)
High-Fat Meal SD Cohort: Solution Formulation (Part 3)
Participants will receive GDC-0310 single ascending dose based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a high-fat meal after a 8-hour/overnight fast using solution on Day 1 of the treatment period (5 days) in an additional cohort of Part 3.
干预措施: GDC-0310 (Drug)
Low-Fat Meal SD Cohort: PIC (Part 1)
Participants will receive GDC-0310 single ascending dose given orally using PIC based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a low-fat meal after an 8-hour/overnight fast using PIC on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.
干预措施: GDC-0310 (Drug)
Low-Fat Meal SD Cohort: Solution Formulation (Part 3)
Participants will receive GDC-0310 single ascending dose given orally using PIC based on PK results from earlier SD cohorts up to an established dose yielding at least a 2-fold exposure margin to the MTD administered orally following a low-fat meal after an 8-hour/overnight fast using solution on Day 1 of the treatment period (5 days) in an additional cohort of Part 1.
干预措施: GDC-0310 (Drug)
MD Cohort: PIC (Part 2)
Participants will receive multiple ascending dose administered orally using PIC from Day 1 to Day 13 twice daily (BID) or may even be thrice daily (TID) or four times a day (QD) depending on clinical PK, followed by morning dose on Day 14 in 7 cohorts of Part 2.
干预措施: GDC-0310 (Drug)
MD Cohort: Solution Formulation (Part 4)
Participants will receive multiple ascending dose in fed or fast condition, administered orally using solution from Day 1 to Day 13 BID or may even be TID or QD depending on clinical PK, followed by morning dose on Day 14 in 7 cohorts of Part 2.
干预措施: GDC-0310 (Drug)
Placebo PIC
Participants will receive placebo matched to GDC-0310 single or multiple ascending dose administered orally in the fasted (SD cohorts) or fed state using PIC on Day 1 of the treatment period (5 days) to the SD cohorts and from Day 1 to 14 BID or may even be TID or QD depending on clinical PK, to the MD cohorts.
干预措施: Placebo (Drug)
Placebo Solution
Participants will receive placebo matched to GDC-0310 single or multiple ascending dose administered orally in the fasted (SD cohorts) or fed state using PIC on Day 1 of the treatment period (5 days) to the SD cohorts and from Day 1 to 14 BID or may even be TID or QD depending on clinical PK, to the MD cohorts.
干预措施: Placebo (Drug)
SD Cohort: PIC (Part 1)
Participants will receive GDC-0310 single ascending dose administered orally in the fasted state using PIC on Day 1 of the treatment period (5 days) in the 9 cohorts of Part 1.
干预措施: GDC-0310 (Drug)
SD Cohort: Solution Formulation (Part 3)
Participants will receive GDC-0310 single ascending dose administered orally in the fasted state using solution formulation on Day 1 of the treatment period (5 days) in the 9 cohorts of Part 3.
干预措施: GDC-0310 (Drug)
结局指标
主要结局
Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
时间窗: Baseline up to Month 9
次要结局
- Apparent Terminal Elimination Rate Constant (ke) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Apparent Terminal Volume of Distribution (Vz/F) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Apparent Terminal Half-Life (t1/2) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- PK Dose Proportionality as Assessed With AUC of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Accumulation Ratio for MD Cohort(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Maximum Plasma Concentration (Cmax) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Minimum Plasma Concentration (Cmin) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Time to Maximum Plasma Concentration (tmax) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Area Under the Concentration-Time Curve (AUC) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Apparent Clearance (CL/F) of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))
- Pharmacokinetics (PK) Dose Proportionality as Assessed With Cmax of GDC-0310(Pre dose up to Day 15 (detailed timeframe has been reported in the description))