A Phase 1, Three-part, Part-randomised, Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Different Formulations of Tricaprilin, to Include Single-dose, Food Effect, and Titration Tolerability, in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics, safety, and tolerability of new liquid formulations of tricaprilin, with the aim of finding a suitable formulation to advance in development. This is a three-part, part-randomised study that include single-dose, food effect, and titration tolerability in up to 80 healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
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
- •Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Participants who are overtly healthy (in the opinion of the Investigator) as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Body weight ≥45 kg and body mass index (BMI) within the range 18.0 - 32.0 kg/m2 (inclusive).
- •Male and female
- •Agrees to comply with study procedures including blood draws, confinement to clinic, meal requirements
- •Continuous non-smoker or infrequent smoker (no more than 10 cigarettes per week for at least 3 months prior to Screening)
排除标准
- •History of, or current gastrointestinal (GI) conditions constituting a risk when taking the study treatment; or interfering with the interpretation of data, based on the Investigator's judgement
- •Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen [up to 2 g per day], hormone replacement therapy and hormonal contraception are permitted).
- •Participants on a ketogenic diet, low-fat diet or actively using medium chain triglycerides, ketone esters, or other ketogenic products.
研究组 & 干预措施
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-1202 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-01 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-02 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-03 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-04 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-05 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-06 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-07 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-08 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-09 (Drug)
Part 1 (Formulation Optimisation)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided 30 minutes after study drug administration. There will be 4 different formulations of the study drug and participants will be randomised to one of 4 sequences. There will be a washout of 2 days between each administration.
干预措施: AC-OLE-010 (Drug)
Part 2 (Placebo Assessment)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment.
Participants are randomised to 1 of 2 sequences (tricaprilin formulation - matching placebo; matching placebo - tricaprilin formulation) with a 2-day washout between periods.
干预措施: AC-OLE-P (Drug)
Part 3 (Titration Tolerability)
Study drug administered orally after an overnight fast (minimum 8 hours). A standard breakfast will be provided either 30 minutes before or after study drug administration, depending on the results of the food effect assessment.
Participants will be randomised to either study drug or the matching placebo.
干预措施: AC-OLE-P (Drug)
结局指标
主要结局
Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)
时间窗: 0 to 8 hours post-dose
Cmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)
Area under the concentration-time curve (AUC) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)
时间窗: 0 to 8 hours post-dose
AUC will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)
Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) after single-dose administration of tricaprilin and placebo formulations (Part 1, Part 2)
时间窗: 0 to 8 hours post-dose
Tmax will be calculated from PK concentrations of total ketones (B-hydroxybutyrate and Acetoacetate)
次要结局
- Gastrointestinal side effects of single-dose administration of each of tricaprilin formulations and the placebo formulation (Parts 1, 2) assessed using the Baxter Retching Faces Scale(Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose)
- Area under the concentration-time curve (AUC) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)(Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose)
- Incidence of treatment emergent adverse events(Baseline to end of treatment period)
- Gastrointestinal side effects of single-dose administration of each of tricaprilin formulations and the placebo formulation (Parts 1, 2) assessed using the Pain Numerical Rating Scale(Pre-dose, 0.5, 1, 1.5, 2, 3 hours post-dose)
- Maximum observed concentration (Cmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)(Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose)
- Time of maximum concentration (Tmax) of total ketones (β-hydroxybutyrate and acetoacetate) of tricaprilin and placebo formulations following a titration scheme (Part 3)(Days 15 and 21: 0 to 8 hours post-dose; Day 27: 0 to 24 hours post-dose)