A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered AL-034 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation (Part 1) and After Multiple Ascending Doses (Part 2) in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Part 2: Number of Participants With AEs by Severity
研究概览
简要总结
This is a Phase 1 first-in-human (FIH) study evaluating single and multiple dose administration of AL-034 in healthy adult participants. The aim is to examine the safety (including pharmacodynamic [PD] biomarker assessments), tolerability, and pharmacokinetics (PK) of increasing single ascending doses (SADs) (Part 1) and multiple ascending doses (MADs) (Part 2) of AL-034. The potential food effect will be investigated in healthy adult participants at one or optionally 2 single dose level(s).
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part 1: Single Ascending Dose (SAD)
Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram [mg]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034.
干预措施: AL-034 (Drug)
Part 1: Single Ascending Dose (SAD)
Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram [mg]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034.
干预措施: Placebo (Drug)
Part 2: Multiple-Dose Administration (MAD)
Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1.
干预措施: AL-034 (Drug)
Part 2: Multiple-Dose Administration (MAD)
Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2: Number of Participants With AEs by Severity
时间窗: Approximately up to 12 weeks
Severity of AEs will be graded according to the Division of AIDS (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE).
Part 1: Number of Participants with Holter Monitoring Abnormalities
时间窗: Approximately up to 9 weeks
Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported.
Part 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
时间窗: Approximately up to 9 weeks
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 1: Number of Participants With AEs by Severity
时间窗: Approximately up to 9 weeks
Severity of AEs will be graded according to the Division of Acquired Immune Deficiency Syndrome (DAIDS) Toxicity Grading Scale as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening); and Grade 5 (death related to the AE).
Part 2: Number of Participants with Vital Sign Abnormalities
时间窗: Approximately up to 12 weeks
Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation \[SaO2\] and blood pressure) will be reported.
Part 2: Number of Participants with Laboratory Abnormalities
时间窗: Approximately up to 12 weeks
Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported.
Part 1: Number of Participants with Electrocardiogram (ECG) Abnormalities
时间窗: Approximately up to 9 weeks
Number of participants with electrocardiogram (ECG) abnormalities will be reported.
Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities
时间窗: Approximately up to 12 weeks
Number of participants with electrocardiogram (ECG) abnormalities will be reported.
Part 1: Number of Participants with Vital Sign Abnormalities
时间窗: Approximately up to 9 weeks
Number of participants with vital signs abnormalities (vital signs includes body temperature, pulse rate, respiratory rate, oxygen saturation \[SaO2\] and blood pressure) will be reported.
Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
时间窗: Approximately up to 12 weeks
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Part 1: Number of Participants with Clinically Significant Changes in Physical Examination
时间窗: Approximately up to 9 weeks
Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported.
Part 1: Number of Participants with Cytokine Release Syndrome (CRS) by Severity
时间窗: Approximately up to 9 weeks
Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening).
Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Repeated Dose Administration
时间窗: Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose
AUC is the area under the plasma concentration time curve of AL-034 in plasma following MAD administration.
Part 1: AL-034 Concentration in Urine Following a Single Dose Administration
时间窗: Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose
Concentration in urine of AL-034 following a single dose administration will be determined.
Part 2: Number of Participants with Clinically Significant Changes in Physical Examination
时间窗: Approximately up to 12 weeks
Number of participants with clinically significant changes in the physical examination (including height, body weight measurement, and skin examination) will be reported.
Part 2: Number of Participants with Holter Monitoring Abnormalities
时间窗: Approximately up to 12 weeks
Number of participants with Holter monitoring abnormalities (related to heart's activity such as rate and rhythm) will be reported.
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fasted State
时间窗: Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
The Cmax is the maximum observed concentration of AL-034 in plasma following single ascending dose (SAD) administration.
Part 1: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fasted State
时间窗: Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
AUC is the area under the plasma concentration time curve of AL-034 in plasma following SAD administration.
Part 1: Number of Participants with Laboratory Abnormalities
时间窗: Approximately up to 9 weeks
Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported.
Part 1: Number of Participants with Cytokine Release Syndrome (CRS)
时间窗: Approximately up to 9 weeks
Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
Part 2: Number of Participants with Cytokine Release Syndrome (CRS)
时间窗: Approximately up to 12 weeks
Number of participants with CRS will be reported. CRS is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath.
Part 2: Number of Participants with Cytokine Release Syndrome (CRS) by Severity
时间窗: Approximately up to 12 weeks
Severity of CRS will be graded according to DAIDS as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); and Grade 4 (potentially life-threatening).
Part 2: AL-034 Concentration in Urine Following Repeated Dose Administration
时间窗: Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose
Concentration in urine of AL-034 following MAD administration will be determined.
Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Repeated Dose Administration
时间窗: Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose
The Cmax is the maximum observed concentration of AL-034 in plasma following multiple ascending dose (MAD) administration.
次要结局
- Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fed State(Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose)
- Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fed State(Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose)