Evaluation of PK of Caprylic Triglyceride Oil, AC-1202, AC-1204, and Axona on Ketone Body Production

Sponsor

Cerecin (Industry)

Overall Status

Completed

CT.gov ID

NCT02833012

Collaborator

Celerion (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare serum ketone body (i.e., total ketones, β hydroxybutyrate, and estimate of acetoacetate) levels after single dose administration of caprylic triglyceride (CT) oil, AC-1202, AC-1204, and Axona®.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Caprylic Triglyceride Oil Drug: AC-1202 Drug: Axona Drug: AC-1204	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Phase 1, Pilot, Single-Dose, 4-Way Crossover Study to Compare the Pharmacokinetics of Caprylic Triglyceride Oil, AC-1202, AC-1204, and Axona on Ketone Body Production

Study Start Date :

Jul 1, 2016

Actual Primary Completion Date :

Sep 1, 2016

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Caprylic Triglyceride Oil, AC-1202, Axona, AC-1204	Drug: Caprylic Triglyceride Oil 10 g Caprylic Triglyceride Oil (10.5 mL) at Hour 0 on Day 1 Drug: AC-1202 60 g AC-1202 (shaken in 180 mL of water) at Hour 0 on Day 1 Drug: Axona 40 g Axona (shaken in 120 mL of water) at Hour 0 on Day 1 Drug: AC-1204 40 g AC-1204 (shaken in 120 mL of water) at Hour 0 on Day 1
Experimental: Group 2 Caprylic Triglyceride Oil, AC-1202, Axona, AC-1204	Drug: Caprylic Triglyceride Oil 10 g Caprylic Triglyceride Oil (10.5 mL) at Hour 0 on Day 1 Drug: AC-1202 60 g AC-1202 (shaken in 180 mL of water) at Hour 0 on Day 1 Drug: Axona 40 g Axona (shaken in 120 mL of water) at Hour 0 on Day 1 Drug: AC-1204 40 g AC-1204 (shaken in 120 mL of water) at Hour 0 on Day 1
Experimental: Group 3 Caprylic Triglyceride Oil, AC-1202, Axona, AC-1204	Drug: Caprylic Triglyceride Oil 10 g Caprylic Triglyceride Oil (10.5 mL) at Hour 0 on Day 1 Drug: AC-1202 60 g AC-1202 (shaken in 180 mL of water) at Hour 0 on Day 1 Drug: Axona 40 g Axona (shaken in 120 mL of water) at Hour 0 on Day 1 Drug: AC-1204 40 g AC-1204 (shaken in 120 mL of water) at Hour 0 on Day 1
Experimental: Group 4 Caprylic Triglyceride Oil, AC-1202, Axona, AC-1204	Drug: Caprylic Triglyceride Oil 10 g Caprylic Triglyceride Oil (10.5 mL) at Hour 0 on Day 1 Drug: AC-1202 60 g AC-1202 (shaken in 180 mL of water) at Hour 0 on Day 1 Drug: Axona 40 g Axona (shaken in 120 mL of water) at Hour 0 on Day 1 Drug: AC-1204 40 g AC-1204 (shaken in 120 mL of water) at Hour 0 on Day 1

Outcome Measures

Primary Outcome Measures

total ketones AUC0-t [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 AUC0-inf [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 AUC%extap [0-24 hours]
Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0-inf)*100
total ketones Cmax [0-24 hours]
Maximum observed concentration
total ketones Kel [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 [0-24 hours]
Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel
total ketones Tmax [0-24 hours]
Time to reach Cmax. If the value occurs at more than one time point, Tmax is defined as the first time point with this value
β hydroxybutyrate AUC0-t [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 [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 [0-24 hours]
Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0-inf)*100
β hydroxybutyrate Cmax [0-24 hours]
Maximum observed concentration
β hydroxybutyrate Kel [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)
β hydroxybutyrate T 1/2 [0-24 hours]
Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel
β hydroxybutyrate Tmax [0-24 hours]
Time to reach Cmax. If the value occurs at more than one time point, Tmax is defined as the first time point with this value
estimate of acetoacetate AUC0-t [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.
estimate of acetoacetate AUC0-inf [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.
estimate of acetoacetate AUC%extap [0-24 hours]
Percent of AUCo-inf extrapolated, represented as (1 - AUC0-t/AUC0-inf)*100
estimate of acetoacetate Cmax [0-24 hours]
Maximum observed concentration
estimate of acetoacetate Kel [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)
estimate of acetoacetate T 1/2 [0-24 hours]
Apparent first-order terminal elimination half-life will be calculated as 0.693/Kel
estimate of acetoacetate Tmax [0-24 hours]
Time to reach Cmax. If the value occurs at more than one time point, Tmax is defined as the first time point with this value

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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 Day -1 of Period 1 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 triglyceride levels must be < 250 mg/dL.
A non-vasectomized subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to Day -1 of Period 1. A subject who has been vasectomized less than 4 months prior to Day -1 of Period 1 must follow the same restrictions as a non vasectomized male).
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 Day -1 of Period 1.
History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, milk, palm or 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.
QTcF interval is >460 msec 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 Day -1 of Period 1 and throughout the study. Acetaminophen (up to 2 g per 24 hour period) 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 Day -1 of Period 1 and throughout the study.
Is lactose intolerant.
Is unable to complete the meal prior to Day -1 of Period 1.
Subject consumed grapefruit or Seville oranges within 14 days prior to Day -1 of Period 1.
Donation of blood or significant blood loss within 56 days prior to Day -1 of Period
Plasma donation within 7 days prior to Day -1 of Period 1.
Participation in another clinical study within 28 days prior to Day -1 of Period 1. 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.