A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The rate of adverse events
研究概览
简要总结
To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects.
详细描述
A randomized, open-label, four-treatment, four-period crossover study in which healthy male subjects received a single dose of each of the following four treatments on four separate dosing days, 7 days apart:
- Oral sodium phenylbutyrate (Buphenyl®) equivalent to 3 g/m2 of 4-phenylbutyric acid (PBA) per dose
- Oral GT4P-F mole equivalents to 3 g/m2 of PBA per dose
- Oral GT4P-API mole equivalents to 3 g/m2 of PBA per dose
- Intravenous 10% sodium phenylacetate plus 10% sodium benzoate (Ammonul®) 2.75 g/m2
Study acquired from Horizon in 2024.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 交叉
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- Subjects were required to fulfill the following criteria in order to participate in the study:
- Males aged 18 to 45 years of age
- Ability to provide written, informed consent before any study-related procedures, and ability, in the opinion of the investigator, to comply with all the requirements of the study
- Subjects who were in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, 12 lead ECG, and vital signs
- Weight within the range of 60-120 kg
排除标准
- Subjects who fulfilled any of the following criteria were excluded from the study:
- Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurologic, immunologic, or psychiatric disorder(s), as determined by the investigator
- Clinically significant abnormal laboratory values (as determined by the investigator)
- Significant illness within 14 days prior to screening
- Any disorder that might significantly interfere with the absorption, distribution, metabolism, or excretion of any drug
- Use of any prescription medication within 14 days prior to screening
- Use of dietary supplements, herbal medicines, vitamins, or over-the-counter medication(s) (with the exception of acetaminophen ≤ 500 mg/day) within 10 days prior to first dosing
- Positive drugs of abuse urine test at screening or pre-dose day (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, methadone)
- Positive alcohol breath test at screening or pre-dose day
- Donation or loss of blood (500 ml or more) within 30 days prior to first dosing, or during the study
- Donation or loss of plasma within 7 days prior to first dosing, or during the study
- History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC)
- History of acquired immunodeficiency syndrome (AIDS) or determined HIV positive at screening
- Use of any investigational drug within 12 weeks prior to first dosing
- Known hypersensitivity to sodium phenylbutyrate or similar drugs
- Previous exposure to sodium phenylbutyrate
研究组 & 干预措施
GT4P-API
GT4P-API was supplied as an odorless, colorless, tasteless oil in 125 ml bottles. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-API was taken orally and washed down with 100 ml of water. GT4P-API was stored at ambient temperature, away from light.
干预措施: HPN-100 (Drug)
GT4P-F
GT4P-F (80% GT4P) was supplied as an odorless, colorless, tasteless liquid oil in 125 ml bottles. This formulation was designed to be mixed in water and create a self-emulsifying suspension, thus administered in water for the trial. The administered dose was calculated to contain the number of moles of PBA equivalent to 3 g/m2 of PBA. GT4P-F was mixed in 50 ml of water, taken orally, and then the cup rinsed with 50 ml of water and taken orally. GT4P-F was stored at ambient temperature away from light.
干预措施: HPN-100 (Drug)
Buphenyl
Sodium phenylbutyrate or Buphenyl® was supplied as a white powder in 250 g bottles. The required amount of powder (equivalent to 3 g/m2 of PBA) was weighed out, mixed in 100 ml of water, and administered orally. Doses were calculated on a weight/volume basis and corrected for sodium content and purity. Buphenyl® was stored at ambient temperature.
干预措施: Buphenyl (Drug)
Ammonul
Ammonul® was supplied as single-use glass vials of 10% sodium phenylacetate and 10% sodium benzoate for intravenous injection. Ammonul® was diluted before use with sterile dextrose injection 10% to a concentration of 9 mg/ml. Once diluted it was kept at room temperature and used within 24 hours. The dose was 2.75 g/m2 and was administered as an intravenous infusion over a 120-minute period. Ammonul® was stored at 25°C, within a range of 15-30°C.
干预措施: Ammonul (Drug)
结局指标
主要结局
The rate of adverse events
时间窗: 33 Days
次要结局
未报告次要终点
研究者
研究点 (1)
标识符
- NCT 编号
- NCT00977600
- 其他研究编号
- UP 1204-001
日期
- 首次提交
- (17年前)
- 首次发布
- (17年前)
- 研究完成日期
- 最近核实
- 最近更新
- (2年前)
监管与共享
- FDA 监管药物
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.