Clinical trial NCT02747602: Evaluation of PK of AC1204 v Caprylic Triglyceride Oil Incl Food Effect on Ketone Body Production
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
Caprylic triglyceride oil
AC-1204
Pharmacokinetic
Ketone body
Lead sponsor: Cerecin
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2016-04-22
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Healthy, adult, male 18-55 years of age, inclusive, at screening.
2. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study.
3. Body mass index (BMI) ≥ 20.0 and ≤ 30.0 kg/m2 at screening.
4. 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.
5. 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).
6. Subjects must agree not to donate sperm from the first dose/dosing until 90 days after dosing.
7. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

1. 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.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
3. 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.
4. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose/dosing.
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, milk, coconut oil, or soy.
6. History or presence of diverticular disease, ulcers, inflammatory bowel disease or recurrent diarrhea or gout.
7. Positive urine drug or alcohol results at screening or check-in.
8. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
9. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
10. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
11. QTc interval is \>460 msec (males) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening.
12. Estimated creatinine clearance ≤80 mL/min at screening.
13. 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.
14. 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.
15. Is lactose intolerant.
16. Is unable to complete the critical meal (i.e., breakfast prior to dosing).
17. Donation of blood or significant blood loss within 56 days prior to the first dose.
18. Plasma donation within 7 days prior to the first dose.
19. 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.

Primary outcomes:
measure: total ketones AUC0-t
timeFrame: 0-24 hours
measure: total ketones AUC0-inf
timeFrame: 0-24 hours
measure: total ketones AUC%extap
timeFrame: 0-24 hours
measure: total ketones Cmax
timeFrame: 0-24 hours
measure: total ketones Kel
timeFrame: 0-24 hours
measure: total ketones T 1/2
timeFrame: 0-24 hours
measure: total ketones Tmax
timeFrame: 0-24 hours
measure: β-hydroxybutyrate AUC0-t
timeFrame: 0-24 hours
measure: β-hydroxybutyrate AUC0-inf
timeFrame: 0-24 hours
measure: β-hydroxybutyrate AUC%extap
timeFrame: 0-24 hours
measure: β-hydroxybutyrate Cmax
timeFrame: 0-24 hours
measure: β-hydroxybutyrate Tmax
timeFrame: 0-24 hours
measure: β-hydroxybutyrate Kel
timeFrame: 0-24 hours
measure: β-hydroxybutyrate T 1/2
timeFrame: 0-24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion, Inc
state: Arizona
Study officials:
affiliation: Celerion
name: Geri Poss, MD
role: PRINCIPAL_INVESTIGATOR
References: