A Phase 1, Pilot, Single-Dose, 3-Way Crossover Study to Evaluate the Pharmacokinetic of AC-1204 Versus Caprylic Triglyceride Oil Including the Effect of Food on Ketone Body Production
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- total ketones AUC0-inf
研究概览
简要总结
To compare serum ketone body (i.e., total ketones and β-hydroxybutyrate) levels after administration of AC-1204 versus caprylic triglyceride (CT) oil, both after a standard breakfast.
To evaluate the effect of a high fat diet on serum ketone body levels after administration of CT oil with a high fat breakfast versus a standard breakfast.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male 18-55 years of age, inclusive, at screening.
- •Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study.
- •Body mass index (BMI) ≥ 20.0 and ≤ 30.0 kg/m2 at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. At screening, subjects must have alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) < the upper limit of normal and triglycerides levels < 250 mg/dL.
- •A non-vasectomized subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dose/dosing of study drug. A subject who has been vasectomized less than 4 months prior to study first dose/dosing must follow the same restrictions as a non-vasectomized male).
- •Subjects must agree not to donate sperm from the first dose/dosing until 90 days after dosing.
- •Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.
排除标准
- •Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- •History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose/dosing.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, milk, coconut oil, or soy.
- •History or presence of diverticular disease, ulcers, inflammatory bowel disease or recurrent diarrhea or gout.
- •Positive urine drug or alcohol results at screening or check-in.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
- •Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
- •QTc interval is >460 msec (males) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
- •Estimated creatinine clearance ≤80 mL/min at screening.
- •Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to the first dose and throughout the study. Acetaminophen (up to 2 g per 24 hour period) and medications for the treatment of adverse events may be permitted during the study.
- •Has been on a diet incompatible with the on-study diet, in the opinion of the PI or designee, within the 28 days prior to the first dose and throughout the study.
- •Is lactose intolerant.
- •Is unable to complete the critical meal (i.e., breakfast prior to dosing).
- •Donation of blood or significant blood loss within 56 days prior to the first dose.
- •Plasma donation within 7 days prior to the first dose.
- •Participation in another clinical study within 28 days prior to the first dose. The 28-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
研究组 & 干预措施
Group ABC
AC-1204, caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast
干预措施: AC-1204 (Drug)
Group ABC
AC-1204, caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast
干预措施: caprylic triglyceride oil (standard breakfast) (Drug)
Group ABC
AC-1204, caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast
干预措施: caprylic triglyceride oil (high fat breakfast) (Drug)
Group BCA
caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast, AC-1204
干预措施: AC-1204 (Drug)
Group BCA
caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast, AC-1204
干预措施: caprylic triglyceride oil (standard breakfast) (Drug)
Group BCA
caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast, AC-1204
干预措施: caprylic triglyceride oil (high fat breakfast) (Drug)
Group CAB
caprylic triglyceride high fat breakfast, AC-1204, caprylic triglyceride oil standard breakfast
干预措施: AC-1204 (Drug)
Group CAB
caprylic triglyceride high fat breakfast, AC-1204, caprylic triglyceride oil standard breakfast
干预措施: caprylic triglyceride oil (standard breakfast) (Drug)
Group CAB
caprylic triglyceride high fat breakfast, AC-1204, caprylic triglyceride oil standard breakfast
干预措施: caprylic triglyceride oil (high fat breakfast) (Drug)
结局指标
主要结局
total ketones AUC0-inf
时间窗: 0-24 hours
The area under the concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable serum concentration to the elimination rate constant.
total ketones AUC0-t
时间窗: 0-24 hours
The area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method.
total ketones Tmax
时间窗: 0-24 hours
Time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value
β-hydroxybutyrate AUC0-t
时间窗: 0-24 hours
The area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method.
β-hydroxybutyrate AUC0-inf
时间窗: 0-24 hours
The area under the concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable serum concentration to the elimination rate constant
β-hydroxybutyrate AUC%extap
时间窗: 0-24 hours
Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0- inf)\*100.
β-hydroxybutyrate Cmax
时间窗: 0-24 hours
Maximum observed concentration
β-hydroxybutyrate Tmax
时间窗: 0-24 hours
Time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value
β-hydroxybutyrate T 1/2
时间窗: 0-24 hours
Apparent first-order terminal elimination half-life will be calculated as 0.693/kel.
total ketones AUC%extap
时间窗: 0-24 hours
Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0- inf)\*100
total ketones Cmax
时间窗: 0-24 hours
Maximum observed concentration
total ketones Kel
时间窗: 0-24 hours
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration versus time curve. The parameter will be calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g., three or more non-zero serum concentrations)
total ketones T 1/2
时间窗: 0-24 hours
Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel
β-hydroxybutyrate Kel
时间窗: 0-24 hours
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration versus time curve. The parameter will be calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g., three or more non-zero serum concentrations).
次要结局
未报告次要终点