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Trial registered on ANZCTR


Registration number
ACTRN12620000213943
Ethics application status
Approved
Date submitted
28/01/2020
Date registered
21/02/2020
Date last updated
10/06/2021
Date data sharing statement initially provided
21/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study to evaluate Safety, Tolerability and Pharmacokinetics of Ultramicronized-Palmitoylethanolamide (PEA) in Healthy Subjects.
Scientific title
A Phase 1, randomized, Double-Blind, Placebo-Controlled study to evaluate the Safety, Tolerability and Pharmacokinetics of single and multiple ascending doses of Ultramicronized PEA in normal healthy volunteers.
Secondary ID [1] 300299 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Pain 315914 0
Inflammation 316135 0
Condition category
Condition code
Inflammatory and Immune System 314186 314186 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be administered Ultramicronized PEA or matching placebo tablets in Cohort 1-6 via oral route as below.
Cohort 1- Single dose of 600mg Ultramicronized PEA tablet i.e 1 tablet (n=6) or matching placebo (n=2);
Cohort 2 - Single dose of 1200mg Ultramicronized PEA tablet i.e 2 tablets (under fasting and fed conditions) (n=6) or matching placebo (n=2);
For cohorts dosed under fasting conditions, no food will be allowed from at least 10 hours before until at least 4 hours after dosing. Except for water given with the study drug, no fluids will be allowed from 1 hour before until 1 hour after dosing. There will be a washout period of at least 7 days between dosing of the fasting and the fed periods.
For the fed period of Cohort 2, after a supervised fast of at least 10 hours, subjects will be served a high-fat, high-calorie meal of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. Drug administration will occur approximately 30 minutes after the meal has been started. Except for fluids provided with the breakfast and water given with the study drug, no fluids will be allowed from 1 hour before until 1 hour after dosing.
Cohort 3 - Single dose of 1800mg Ultramicronized PEA tablet i.e 3 tablets (n=6) or matching placebo (n=2);
Cohort 4 - Single dose of 2400mg Ultramicronized PEA tablet i.e 4 tablets (n=6) or matching placebo (n=2);
Cohort 5 - Twice daily dose of 600mg Ultramicronized PEA tablet i.e 1 tablet from Day 1 to Day 6 and once in the morning of Day 7 (n=6) or matching placebo (n=2);
Cohort 6 - Twice daily dose of 1200mg Ultramicronized PEA tablet i.e 2 tablets from Day 1 to Day 6 and once in the morning of Day 7 (n=6) or matching placebo (n=2);
Subjects cannot be enrolled in more than one cohort.

For Part A (Cohort 1-4) Study medication will be administered to each subject with 240 mL of water and a mouth check will be performed to ensure consumption of the medication. In the event that subjects cannot swallow all tablets with 240 mL of water, additional water may be allowed up to a maximum total volume of 400 mL. For Cohort 2, the total volume of water administered for dosing in the fasting period will be recorded and the same volume will be used for dosing in the fed period. Time of dosing will be set equal to the time when the (first) tablet is administered to the subject. The dosing procedure must be completed within 2 minutes.
For Part B (Cohort 5-6), each study drug administration will be separated by approximately 12 hours and should be done at approximately the same time every day.
Intervention code [1] 316583 0
Treatment: Drugs
Comparator / control treatment
Microcellulose capsule
Control group
Placebo

Outcomes
Primary outcome [1] 322562 0
To evaluate the safety and tolerability of ultramicronized PEA following oral administration of single ascending doses and multiple ascending doses in healthy subjects compared to placebo.
Timepoint [1] 322562 0
Cohort 1,2,3,4 will be referred to as Part A of study while Cohort 5,6 will be referred to as Part B of the study.
Physical Examination
Part A: A complete physical examination will be performed at screening and a brief physical examination will be performed on Day 1 and at EOS/ET.
Part B: A complete physical examination will be performed at screening and a brief physical examination will be performed on Day 1, Day 4, Day 7, and at EOS/ET.

Vital Signs
Part A: BP, HR, RR, and OT will be measured at screening and at EOS/ET. OT will be measured on Day 1. BP and HR will be measured at pre-dose on Day 1 and approximately 0.5, 1, 2, 4, 8, and 12 hours post-dose (±15 minutes).
Part B: BP, HR, RR, and OT will be measured at screening and at EOS/ET. OT will be measured on Day 1 and pre-morning dose on Day 4 and Day 7. BP and HR will be measured at pre-morning dose and approximately 0.5, 1, 2, 4, 8, and 12 hours post-morning dose (±15 minutes) on Day 1, Day 4, and Day 7.

ECG
Part A: A 12-lead ECG will be performed at screening, pre-dose on Day 1 and approximately 1, 4, and 12 hours post-dose (±15 minutes), and at EOS/ET.
Part B: A 12-lead ECG will be performed at screening, pre-morning dose and approximately 1, 4, and 12 hours post morning dose (±15 minutes) on Day 1, Day 4, and Day 7, and at EOS/ET.

Lab assessments
1. Pregnancy test: a serum pregnancy test will be performed at screening and a urine pregnancy test will be performed on Day 1 and at EOS/ET.
2. Drug And alcohol Screen: a urine drug screen (amphetamines, methamphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol, cocaine, opiates, PCP, MDMA, methadone) and an alcohol breath test will be performed at screening and on Day 1.
3. Serology: HIV antigen and antibody, HBsAg, and HCV antibody detection will be performed at screening.
4. Follicle-Stimulating Hormone: For post-menopausal females, FSH level will be measured at screening and the post-menopausal status will be confirmed by documented FSH level ?40 mIU/mL.
5. Hematology: Part A: Hematology will be performed at screening, on Day 1, and at EOS/ET. Part B: Hematology will be performed at screening, on Day 1, Day 4, Day 7, and at EOS/ET.
6. Biochemistry: Part A: Biochemistry will be performed at screening, on Day 1, and at EOS/ET. Part B: Biochemistry will be performed at screening, on Day 1, Day 4, Day 7, and at EOS/ET.
7. Urinalysis Part A: Urinalysis will be performed at screening, on Day 1, and at EOS/ET. Part B: Urinalysis will be performed at screening, on Day 1, Day 4, Day 7, and at EOS/ET.
Secondary outcome [1] 378946 0
To characterize the pharmacokinetic (PK) profile of ultramicronized PEA following single and multiple oral doses in healthy subjects.
For single dose : AUC0-t, Cmax, Tmax, AUC0-inf, Residual area, T½ el, Kel, Cl/F, and Vd/F
will be evaluated.
For multiple dose : Day 1: AUC0-12, Cmax, and Tmax and
Day 7: AUC0-t, Cmax ss, Tmax ss, Cmin ss, AUC0- t, AUC0-inf, Residual Area, T½ el, Kel, Clss/F, and Vd ss/F will be measured.
Timepoint [1] 378946 0
For Single oral dose - PK Blood samples will be collected at pre-dose and 5, 10, 15, 20, 30, and 45 minutes and 1, 1.25, 1.5, 1,75, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose.
For Multiple oral dose - PK Blood samples will be collected at pre-morning dose and 5, 10, 15, 20, 30, and 45 minutes, and 1, 1.25, 1.5, 1,75, 2, 2.5, 3, 4, 6, 8, and 12 hours post-morning dose on Day 1 and Day 7, and at pre-morning dose on Days 4, 5, and 6.
Secondary outcome [2] 378947 0
To evaluate the effect of food on the absorption of ultramicronized PEA.
Timepoint [2] 378947 0
Subjects from Cohort 2 will receive the study drug under both fasting (in a first period) and fed conditions (in a second period). There will be a washout period of at least 7 days between dosing of the fasting and the fed periods.
PK Blood samples will be collected at pre-dose and 5, 10, 15, 20, 30, and 45 minutes and 1, 1.25, 1.5, 1,75, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose (in each period for Cohort 2).

Eligibility
Key inclusion criteria
1. Male or female, light smoker (no more than 9 cigarettes or equivalent daily) or non-smoker, healthy subjects, aged 18 to 65 years inclusive.
2. Healthy is defined as
a) the absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
b) the absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
3. Body mass index of >18.5 to <32.0 kg/m2.
4. Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized since at least 6 months) must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after (the last) study drug administration:
a) simultaneous use of intra-uterine contraceptive device, placed at least 4 weeks prior to (the first) study drug administration, and condom for the male partner.
b) simultaneous use of hormonal contraceptives, started at least 4 weeks prior to (the first) study drug administration and must agree to use the same hormonal contraceptive throughout the study, and condom for the male partner.
c) simultaneous use of diaphragm or cervical cap and male condom for the male partner, started at least 21 days prior to (the first) study drug administration.
5. Male subjects who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from (the first) study drug administration and for 90 days after (the last) study drug administration:
a) simultaneous use of a male condom and, for the female partner, intra-uterine contraceptive device or hormonal contraceptives used since at least 4 weeks.
b) simultaneous use of a male condom and, for the female partner, a diaphragm or cervical cap.
6. Male subjects (including men who have had a vasectomy) with a pregnant partner must agree to use a condom from (the first) study drug administration and for 90 days after (the last) study drug administration.
7. Male subjects must be willing not to donate sperm for 90 days following (the last) study drug administration.
8. Capable of consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1.Any clinically significant abnormality at physical examination.
2. Any laboratory test results deemed clinically significant by the Investigator or positive test for HIV, HBsAg, or HCV found during medical screening.
3. Positive pregnancy test at screening or Day 1.
4. Positive urine drug screen or alcohol breath test at screening or Day 1.
5. History of allergic reactions to PEA or other related drugs, or to any excipient in the formulation.
6. Clinically significant ECG abnormalities or vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm, or RR less than 10 or over 22 bpm) at screening.
7. History of significant drug abuse within 1 year prior to screening or use of soft drugs (such as marijuana) within 1 month prior to the screening or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
8. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit equals to 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
9. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
10. Use of medications for the timeframes specified below, with the exception of hormonal contraceptives and medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption):
a) prescription medications within 14 days prior to (the first) dosing;
b) over-the-counter products and natural health products (including herbal remedies such as St. John’s wort, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to (the first) dosing, with the exception of the occasional use of acetaminophen (up to 2 g daily);
c) depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to (the first) dosing;
11. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
12. Breast-feeding subject.
13. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Designated unblinded pharmacy personnel at the clinical site not directly involved with the clinical aspects of the trial will prepare, store, and dispense the study medication in a blinded manner, according to the randomization scheme.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e computerized sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Safety and tolerability data will be reported using descriptive statistics. No inferential statistical analysis of safety data is planned.

For PK parameters-Descriptive statistics (arithmetic and geometric means, standard deviation [SD], coefficient of variation [CV%], minimum [Min], maximum [Max], and median) of the plasma concentrations versus time will be presented.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/04/2020
Actual
7/04/2020
Date of last participant enrolment
Anticipated
16/06/2020
Actual
10/06/2020
Date of last data collection
Anticipated
17/06/2020
Actual
17/06/2020
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 304721 0
Commercial sector/Industry
Name [1] 304721 0
FSD Pharma Inc.
Country [1] 304721 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
FSD Pharma Inc.
Address
520 William Street
Cobourd, ON K9A 3A5
Country
Canada
Secondary sponsor category [1] 305059 0
Commercial sector/Industry
Name [1] 305059 0
INCResearch Australia Pty Ltd
Address [1] 305059 0
159 Port Road, Hindmarsh SA 5007
Country [1] 305059 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305147 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 305147 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 305147 0
Australia
Date submitted for ethics approval [1] 305147 0
05/02/2020
Approval date [1] 305147 0
04/03/2020
Ethics approval number [1] 305147 0

Summary
Brief summary
This study of ultramicronized PEA (particle size between 0.6 and 10 µm) will investigate the safety, tolerability, PK of single and multiple ascending doses of ultramicronized PEA compared to placebo in healthy subjects.
The effect of food on the absorption of the ultramicronized PEA will also be assessed..
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99394 0
Dr Jason Lickliter
Address 99394 0
Nucleus Network Pty Ltd,
Level 1, 484 St Kilda Road
Melbourne VIC 3004
Country 99394 0
Australia
Phone 99394 0
+61 390768960
Fax 99394 0
Email 99394 0
[email protected]
Contact person for public queries
Name 99395 0
Jason Lickliter
Address 99395 0
Nucleus Network Pty Ltd,
Level 1, 484 St Kilda Road
Melbourne VIC 3004
Country 99395 0
Australia
Phone 99395 0
+61 390768960
Fax 99395 0
Email 99395 0
[email protected]
Contact person for scientific queries
Name 99396 0
Sandra Lottes
Address 99396 0
FSD Pharma
520 William Street
Cobourd, ON K9A 3A5
Country 99396 0
Canada
Phone 99396 0
+16092384448
Fax 99396 0
Email 99396 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Protected as per data privacy law


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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