NCT07241234招募中1 期
A Phase 1b, Open-label, Multicenter, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of AG-181 in Subjects With Phenylketonuria
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug
研究概览
简要总结
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of PKU, defined as documented presence of 2 mutant alleles in the phenylalanine hydroxylase (PAH) gene, of which at least 1 is the R408W mutation, as determined during Screening per the genotyping performed by the study central genotyping laboratory.
- •At least 1 plasma Phe concentration greater than (>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing informed consent.
- •Average concentration of plasma Phe > 600 μmol/L in Phe samples taken during Screening, with no individual assessment below 360 μmol/L. Any Phe samples taken after Day -20 will not be included.
- •Body mass index (BMI) greater than or equal to (≥) 18.0 kilograms per meter square (kg/m^2) to lesser than or equal to (≤) 35.0 kg/m^2 and weight ≥ 50 kilograms (kg) at any time during the Screening Period.
- •Documented approval from a dietitian confirming that the subject can maintain their diet consistent in protein and Phe intake throughout the study as outlined in the Diet Manual.
排除标准
- •Prior exposure to AG-
- •Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥ 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug.
- •Receiving products that are strong inhibitors or strong inducers of cytochrome P450 CYP1A2, CYP2C8, or CYP3A that have not been stopped for ≥ 28 days before administration of the first dose of study drug.
- •Receiving treatment with an acid-reducing agent, including but not limited to proton pump inhibitors and H2 blockers. Short-acting acid-reducing agents such as calcium carbonate are permitted.
- •Any preexisting condition that could (in the opinion of the Investigator) interfere with gastrointestinal anatomy or motility that may disrupt the absorption, metabolism, and/or excretion of the study drug.
- •Any preexisting condition that could (in the opinion of the Investigator) interfere with hepatic or renal function that may disrupt the absorption, metabolism, and/or excretion of the study drug.
- •Inability to tolerate oral medication.
- •Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening.
研究组 & 干预措施
Cohort 1: AG-181
Experimental
Subjects will receive AG-181 from Day 1 to Day 28.
干预措施: AG-181 (Drug)
Cohort 2 (Optional Cohort): AG-181
Experimental
Subjects will receive AG-181.
干预措施: AG-181 (Drug)
结局指标
主要结局
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) by Type, Severity, and Relationship to the Study Drug
时间窗: Up to Day 42
次要结局
- Maximum Concentration (Cmax) of AG-181(Up to Day 28)
- Time to Maximum (Peak) Concentration (Tmax) of AG-181(Up to Day 28)
- Area Under the Concentration-Time Curve (AUC) of AG-181(Up to Day 28)
- Apparent Total Body Clearance (CL/F) of AG-181(Up to Day 28)
- Change From Baseline in Phenylalanine (Phe) Concentration(Baseline up to Day 28)
- Plasma Concentration of AG-181(Up to Day 28)
- Apparent Volume of Distribution in the Terminal Phase (Vz/F) of AG-181(Up to Day 28)
研究者
研究点 (4)
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