Clinical trial NCT03063645: Study to Compare the Pharmacokinetics of AC 1202 and Two Doses of AC-SD-01 on Ketone Body Production
Official title: A Phase 1, Pilot, Single-Dose, 3-Way Crossover Study to Compare the Pharmacokinetics of AC 1202 and Two Doses of AC-SD-01 on Ketone Body Production
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteer
AC-1202
AC-SD-01
Pharacokinetic
ketone body
Lead sponsor: Cerecin
Sponsor class: INDUSTRY
Collaborators: name: Celerion
First posted: 2017-02-24
Enrollment: 17
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 16 healthy subjects enrolled, each subject will receive 1 dose of each treatment, with a 2 day washout in between.
Primary purpose: OTHER

Brief summary: To compare serum ketone body (i.e., total ketones, β hydroxybutyrate, and estimate of acetoacetate) levels after single dose administration of AC-1202 and 2 doses of AC-SD-01.


Eligibility criteria: Inclusion Criteria:

1. Healthy, adult, male 19-55 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.
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 triglyceride levels must be \< 250 mg/dL.
5. 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).
6. 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 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 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. QTcF interval is \> 460 msec or subject 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 Day -1 of Period 1 and throughout the study. Acetaminophen (up to 2 g per 24 hour period) 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 Day -1 of Period 1 and throughout the study.
15. Is lactose intolerant.
16. Is unable to complete the meal prior to Hour 0 on Day -1 of Period 1 and prior to dosing on Day 1 of Period 1.
17. Subject consumed grapefruit or Seville oranges within 14 days prior to Day -1 of Period 1.
18. Donation of blood or significant blood loss within 56 days prior to Day -1 of Period 1.
19. Plasma donation within 7 days prior to Day -1 of Period 1.
20. 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.

Primary outcomes:
measure: total ketones AUC0-t
timeFrame: 0-24 hrs
measure: total ketones AUC0-inf
timeFrame: 0-24 hrs
measure: total ketones AUC%extap
timeFrame: 0-24 hrs
measure: total ketones Cmax
timeFrame: 0-24 hrs
measure: total ketones Kel
timeFrame: 0-24 hrs
measure: total ketones T 1/2
timeFrame: 0-24 hrs
measure: total ketones Tmax
timeFrame: 0-24 hrs
measure: β hydroxybutyrate AUC0-t
timeFrame: 0-24 hrs
measure: β hydroxybutyrate AUC0-inf
timeFrame: 0-24 hrs
measure: β hydroxybutyrate AUC%extap
timeFrame: 0-24 hrs
measure: β hydroxybutyrate Cmax
timeFrame: 0-24 hrs
measure: β hydroxybutyrate Kel
timeFrame: 0-24 hrs
measure: β hydroxybutyrate T 1/2
timeFrame: 0-24 hrs
measure: β hydroxybutyrate Tmax
timeFrame: 0-24 hrs
measure: estimate of acetoacetate AUC0-t
timeFrame: 0-24 hrs
measure: estimate of acetoacetate AUC0-inf
timeFrame: 0-24 hrs
measure: estimate of acetoacetate AUC%extap
timeFrame: 0-24 hrs
measure: estimate of acetoacetate Cmax
timeFrame: 0-24 hrs
measure: estimate of acetoacetate Kel
timeFrame: 0-24 hrs
measure: estimate of acetoacetate T 1/2
timeFrame: 0-24 hrs
measure: estimate of acetoacetate Tmax
timeFrame: 0-24 hrs
Secondary outcomes:
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Celerion
name: Charles Tomek, MD
role: PRINCIPAL_INVESTIGATOR
References: