A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single- and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 10
- 主要终点
- Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
This first-in-human, double-blind, placebo-controlled Phase I study will be conducted in participants with amyotrophic lateral sclerosis (ALS) to explore safety, tolerability, and pharmacokinetic (PK) properties of GDC-0134. It will include three components: a Single-Ascending-Dose (SAD) stage, a Multiple-Ascending-Dose (MAD) stage, and an Open-Label Safety Expansion (OSE) stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants with a diagnosis of possible, laboratory-supported probable, probable, or definite ALS according to modified El Escorial criteria
- •Upright forced vital capacity of at least 50 percent (%)
- •Ability to fast from food for 8 hours prior to dosing and 2 hours after dosing
排除标准
- •Currently taking riluzole unless on a stable dose for the 3 months prior to Day -1 and without current liver enzyme or liver function abnormalities
- •Currently taking edaravone unless after completion of at least the second 14-day drug-treatment period, as long as Day 1 occurs during a drug-free period at least 24 hours after the last edaravone dose and at least 5 days prior to the first dose of the next cycle
- •Positive for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody
- •Clinically significant thrombocytopenia
- •Currently taking nutritional/herbal supplements, except for over-the-counter vitamins that are within Recommended Dietary Allowance (RDA), unless discontinued at least 7 days prior to Day -1, except upon approval of both the investigator and Sponsor
- •For participants participating in a designated drug-drug interaction (DDI) cohort in the MAD stage of the study, who require midazolam/caffeine administration: known allergy, religious prohibition, or other condition limiting midazolam or caffeine administration
研究组 & 干预措施
SAD Stage: GDC-0134
Participants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg).
干预措施: Rabeprazole (Drug)
SAD Stage: Placebo
Participants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg.
干预措施: Placebo (Drug)
SAD Stage: GDC-0134
Participants in multiple cohorts and treatment periods will receive single doses of GDC-0134 oral capsules under fed/fasting conditions. To study the effect of proton pump inhibitor (PPI) medication rabeprazole on PK properties of GDC-0134, few participants may receive rabeprazole 20 milligrams (mg).
干预措施: GDC-0134 (Drug)
SAD Stage: Placebo
Participants in multiple cohorts and treatment periods will receive placebo matching to GDC-0134 under fed/fasting conditions. Few participants may receive rabeprazole 20 mg.
干预措施: Rabeprazole (Drug)
MAD Stage: GDC-0134
Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: GDC-0134 (Drug)
MAD Stage: GDC-0134
Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: Midazolam (Drug)
MAD Stage: GDC-0134
Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: Caffeine (Drug)
MAD Stage: Placebo
Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: Placebo (Drug)
MAD Stage: Placebo
Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: Midazolam (Drug)
MAD Stage: Placebo
Participants will receive placebo matching to GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
干预措施: Caffeine (Drug)
Open-Label Safety Expansion (OSE)
Participants will receive GDC-0134 at a dose determined by the corresponding MAD cohort.
干预措施: GDC-0134 (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs)
时间窗: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
时间窗: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Laboratory Abnormalities
时间窗: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Vital Signs Abnormalities
时间窗: From randomization up to approximately 48 months
Percentage of Participants With Clinically Significant Abnormalities in Physical Examination Findings
时间窗: From randomization up to approximately 48 months
次要结局
- Dose Normalized AUC (AUC/Dose) of GDC-0134(From Day 1 up to 28 days after last dose)
- Apparent Terminal Half-Life (t1/2) of GDC-0134(From Day 1 up to 28 days after last dose)
- Apparent Terminal Volume of Distribution (Vz/F) of GDC-0134(From Day 1 up to 28 days after last dose)
- PK-Dose Proportionality of GDC-0134 as Assessed With Cmax and AUC(From Day 1 up to 28 days after last dose)
- t1/2 of 1-Hydroxymidazolam (Metabolite of Midazolam)(From Day -1 up to 28 days after last dose)
- Time to Maximum Plasma Concentration (tmax) of GDC-0134(From Day 1 up to 28 days after last dose)
- t1/2 of Midazolam(From Day -1 up to 28 days after last dose)
- Maximum Plasma Concentration (Cmax) of GDC-0134(From Day 1 up to 28 days after last dose)
- Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0134(From Day 1 up to 28 days after last dose)
- Accumulation Ratio of GDC-0134(From Day 1 up to 28 days after last dose)
- t1/2 of Paraxanthine (Metabolite of Caffeine)(From Day -1 up to 28 days after last dose)
- Apparent Clearance (CL/F) of GDC-0134(From Day 1 up to 28 days after last dose)
- Dose Normalized Cmax (Cmax/Dose) of GDC-0134(From Day 1 up to 28 days after last dose)
- t1/2 of Caffeine(From Day -1 up to 28 days after last dose)