Medical Food Formulation Pharmacokinetic (PK) Study in Medium Chain Triglycerides

A Phase 1, Single-Center, Pilot, Single-Dose, 6-Way Crossover Study to Compare Six Formulations of Medium Chain Triglycerides on the Pharmacokinetics of Ketone Body Production

This is a Phase I, open label, randomized, 6-way crossover, pilot PK study

Study Overview

• Status: Withdrawn
• Conditions: Alzheimer Disease
• Intervention / Treatment: Other: MCTprocal medical food; Other: Milk/tricaprilin oil blend; Other: AC-1207; Other: AC-1205; Other: AC-1206; Drug: AC-1202

Detailed Description

12 healthy, male subjects enrolled, subject will be randomized to receive a single dose of one of six treatment, with a 2 day washout in between each dosing period.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Day -1 of Period 1 and throughout the study based on self-reporting.
3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 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 triglyceride levels must be < 250 mg/dL.
5. Hemoglobin levels ≥ the lower limit of normal at Screening and Day -1 of Period 1.
6. 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).
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 year prior to Day -1 of Period 1.
5. History or presence of galactosemia or hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, milk, palm or coconut oil, or soy.
6. History or presence of symptomatic diverticular disease, uncontrolled gastroesophageal reflux disease, ulcers, inflammatory bowel disease, irritable bowel syndrome or recurrent diarrhea, or gout.
7. Positive urine drug results at Screening or Check-in.
8. Positive alcohol results at Screening or Check-in. One repeat assessment is permitted.
9. Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
10. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening. One repeat assessment is permitted.
11. Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening.
12. QTcF interval is >460 msec or subject has ECG findings deemed abnormal with clinical significance by the PI or designee at Screening.
13. Estimated creatinine clearance ≤ 80 mL/min at Screening.
14. 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 hours) may be permitted during the study.
15. 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.
16. Has been following a ketogenic diet, in the opinion of the PI or designee, within 2 weeks prior to Day -1 of Period 1.
17. Is lactose intolerant.
18. Is unable to complete the standard breakfast prior to dosing on Day 1 of each Period.
19. Donation of blood or significant blood loss within 56 days prior to Day -1 of Period 1.
20. Plasma donation within 7 days prior to Day -1 of Period 1.
21. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MCTprocal medical food; Vitaflo MCTprocal, single dose (20 g MCT)	Other: MCTprocal medical food; 32 g MCTprocal (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1
Active Comparator: Milk/tricaprilin oil blend; Lactose-free milk and tricaprilin oil, blended,single dose (20 g tricaprilin)	Other: Milk/tricaprilin oil blend; 154 mL of lactose-free skim milk/21 mL of tricaprilin oil blended and then mixed in 180 mL of water at Hour 0 Day 1
Active Comparator: AC-1207; AC-1207 liquid, single dose (20 g tricaprilin)	Other: AC-1207; AC-1207 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1
Active Comparator: AC-1205; AC-1205 liquid, single dose (20 g tricaprilin)	Other: AC-1205; AC-1205 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1
Active Comparator: AC-1206; AC-1206 liquid, single dose (20 g tricaprilin)	Other: AC-1206; AC-1206 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1
Experimental: AC-1202; AC-1206 liquid, single dose (20 g tricaprilin)	Drug: AC-1202; AC-1202 (20 g MCT) mixed in 240 mL of water at Hour 0 Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total ketones	Area Under the Curve (AUC) AUC 0 - last	1 day
Total ketones	AUC 0 - 4	1 day
Total ketones	AUC 0 - 6	1 day
Total ketones	AUC 0 - 8	1 day
Total ketones	Maximum Plasma Concentration (Cmax)	1 day
B-hydroxybutyrate	AUC 0 - last	1 day
B-hydroxybutyrate	AUC 0 - 4	1 day
B-hydroxybutyrate	AUC 0 - 6	1 day
B-hydroxybutyrate	AUC 0 - 8	1 day
B-hydroxybutyrate	Cmax	1 day
Acetoacetate	AUC 0 - last	1 day
Acetoacetate	AUC 0 - 4	1 day
Acetoacetate	AUC 0 - 6	1 day
Acetoacetate	AUC 0 - 8	1 day
Acetoacetate	Cmax	1 day

Collaborators and Investigators

• Sponsor: Cerecin

Study record dates

Study Major Dates

• Study Start (Anticipated): February 13, 2019
• Primary Completion (Anticipated): April 16, 2019
• Study Completion (Anticipated): April 16, 2019

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): September 27, 2018
• Last Update Submitted That Met QC Criteria: September 25, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AX-18-018_PK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes