Evaluation of PK of AC1204 v Caprylic Triglyceride Oil Incl Food Effect on Ketone Body Production

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: AC-1204
* Drug: caprylic triglyceride oil (standard breakfast)
* Drug: caprylic triglyceride oil (high fat breakfast)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group ABC<br>AC-1204, caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast | Drug: AC-1204<br>* 40 g (120 mL) AC-1204 administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (standard breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (high fat breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a high fat breakfast.<br>|
| Experimental: Group BCA<br>caprylic triglyceride oil standard breakfast, caprylic triglyceride high fat breakfast, AC-1204 | Drug: AC-1204<br>* 40 g (120 mL) AC-1204 administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (standard breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (high fat breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a high fat breakfast.<br>|
| Experimental: Group CAB<br>caprylic triglyceride high fat breakfast, AC-1204, caprylic triglyceride oil standard breakfast | Drug: AC-1204<br>* 40 g (120 mL) AC-1204 administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (standard breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a standard breakfast.<br>Drug: caprylic triglyceride oil (high fat breakfast)<br>* 20 g CT oil (21 mL) administered 30 minutes after the start of a high fat breakfast.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total ketones AUC0-t | The area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method. | 0-24 hours | 
| total ketones AUC0-inf | 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. | 0-24 hours | 
| total ketones AUC%extap | Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0- inf)*100 | 0-24 hours | 
| total ketones Cmax | Maximum observed concentration | 0-24 hours | 
| total ketones Kel | 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) | 0-24 hours | 
| total ketones T 1/2 | Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel | 0-24 hours | 
| total ketones Tmax | 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 | 0-24 hours | 
| β-hydroxybutyrate AUC0-t | The area under the concentration-time curve, from time 0 to the last observed non-zero concentration, as calculated by the linear trapezoidal method. | 0-24 hours | 
| β-hydroxybutyrate AUC0-inf | 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 | 0-24 hours | 
| β-hydroxybutyrate AUC%extap | Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0- inf)*100. | 0-24 hours | 
| β-hydroxybutyrate Cmax | Maximum observed concentration | 0-24 hours | 
| β-hydroxybutyrate Tmax | 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 | 0-24 hours | 
| β-hydroxybutyrate Kel | 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). | 0-24 hours | 
| β-hydroxybutyrate T 1/2 | Apparent first-order terminal elimination half-life will be calculated as 0.693/kel. | 0-24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, Caprylic triglyceride oil, AC-1204, Pharmacokinetic, Ketone body