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Trial registered on ANZCTR


Registration number
ACTRN12618001390279p
Ethics application status
Submitted, not yet approved
Date submitted
14/08/2018
Date registered
20/08/2018
Date last updated
21/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety and pharmacokinetics (the measure of how the human body processes a substance) of EHP-101 when administered orally to healthy participants
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics and Food Effect of Single Ascending Doses and Multiple Ascending Doses of EHP-101 in Healthy Subjects
Secondary ID [1] 295656 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 308905 0
Systemic Sclerosis 309251 0
Condition category
Condition code
Neurological 307809 307809 0 0
Multiple sclerosis
Inflammatory and Immune System 308065 308065 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1 - Single Ascending Dose (SAD)
Cohort 1: Single dose of 0.91 mg oral EHP-101 liquid or placebo
Cohort 2: Single dose of 3 mg oral EHP-101 liquid or placebo
Cohort 3: Single dose of 9 mg oral EHP-101 liquid or placebo
Cohort 4: Single dose of 25 mg oral EHP-101 liquid or placebo
Cohort 5: Single dose of 50 mg oral EHP-101 liquid or placebo
Cohort 6: Single dose of 100 mg oral EHP-101 liquid or placebo
Cohort 7: Single dose of 200 mg oral EHP-101 liquid or placebo
Cohort 8: Reserved cohort to study an intermediate dose level or repeating dose level of oral EHP-101 liquid or placebo
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 48 hour post dose assessments (Day 2)

Part 2 - Multiple Ascending Dose (MAD)
Cohort 9: Once daily dose of oral EHP-101 liquid over 7 days, at a dose defined by results from SAD study, or placebo
Cohort 10: Once daily dose of oral EHP-101 liquid over 7 days, at a dose defined by results from SAD study, or placebo
Cohort 11: Once daily dose of oral EHP-101 liquid over 7 days, at a dose defined by results from SAD study, or placebo
Cohort 12: Reserved cohort to study an intermediate dose level or repeating dose level of once daily dose of oral EHP-101 liquid over 7 days, or placebo
Participants will be confined to the study unit from Day -1 and discharged following collection of the 9 day post dose assessments (Day 8)
Each dose level investigated in the MAD part will not exceed the tested dose levels in the SAD part for which safety, tolerability, and PK data have been available and reviewed by the safety review committee.

Note for both Part 1 (SAD) and Part 2 (MAD):
Volunteers will be administered treatment under supervision by qualified staff in clinical confinement. Drug administration compliance and accountability will be checked by monitors during monitoring visits.
Intervention code [1] 301892 0
Treatment: Drugs
Comparator / control treatment
Color-matched liquid oil-based formulation
Control group
Placebo

Outcomes
Primary outcome [1] 306797 0
To determine the safety and tolerability of oral EHP-101 when administered as a single ascending dose (SAD) to healthy subjects. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; monitoring of vital signs; physical examination; ophthalmologic examination; cardiac telemetry; ECG; echocardiography; troponin levels; and any other clinical laboratory parameter abnormalities after a single oral dosing of EHP-101 liquid.
Timepoint [1] 306797 0
Adverse event information will be recorded from the time of informed consent until 30 days after last dose of study drug.
Primary outcome [2] 307015 0
To determine the safety and tolerability of oral EHP-101 when administered as a multiple ascending dose (MAD) to healthy subjects once daily over 7 days. This will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; monitoring of vital signs; physical examination; ophthalmologic examination; cardiac telemetry; ECG; echocardiography; troponin levels; and any other clinical laboratory parameter abnormalities after once daily oral dosing of EHP-101 liquid over 7 days.
Timepoint [2] 307015 0
Adverse event information will be recorded from the time of informed consent until 30 days after last dose of study drug.
Secondary outcome [1] 349675 0
To determine the pharmacokinetic (PK) profile of EHP-101 liquid in healthy subjects following single and multiple oral doses. PK parameters determined are to include C(max), T(max). AUC, K(el), T(1/2), CL/F and Vz/F.
Timepoint [1] 349675 0
PK samples will be collected for plasma analysis during the treatment period at:
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, (144, 168, or 192) hours and 30 days post-dose (Part 1, 20 time points) for single ascending dose.
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120 hours and 30 days post-dose (Part 2, 18 time points) for multiple ascending doses.
Secondary outcome [2] 350362 0
To assess the PK effect(s) of a high-fat, high-calorie meal on the single-dose bioavailability of EHP-101 liquid in healthy subjects. PK parameters determined are to include C(max), T(max). AUC, K(el), t(1/2), CL/F and Vz/F.
Timepoint [2] 350362 0
PK samples will be collected for plasma analysis during the treatment period at:
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120 and 144 (Part 1, 18 time points) for fasting condition.
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours and 30 days post-dose (Part 2, 21 time points) for fed condition.
Secondary outcome [3] 350705 0
To determine the pharmacodynamic (PD) profile of EHP-101 liquid in healthy subjects following single and multiple oral doses. Changes in the relative plasma levels of cytokines, adipokines and angiogenesis-related proteins will be determined using Proteome Profiler Antibody Arrays. This screening will allow for selection of biomarkers for additional ELISA determination which may include erythropoietin, acidic fibroblast growth factor, leptin, platelet-derived growth factor-AA, coagulation factor III, pentraxin 3, vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor, vascular cell adhesion molecule-1, chemerin, chitinase 3-like, resistin, and endostatin in plasma before and after single and multiple dosing.
Timepoint [3] 350705 0
PD samples will be collected for serum analysis during the treatment period at:
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, (144, 168, or 192) hours and 30 days post-dose (Part 1, 20 time points) for single ascending dose.
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120 hours and 30 days post-dose (Part 2, 18 time points) for multiple ascending doses.

Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120 and 144 (Part 1, 18 time points) for fasting condition.
Pre-dose (-10), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours and 30 days post-dose (Part 2, 21 time points) for fed condition.

Eligibility
Key inclusion criteria
Inclusion Criteria: subjects are eligible to be enrolled in the study only if they meet all of the following criteria.
1. Healthy male or female subjects greater than or equal to 18 to less than or equal to 65 years of age.
2. Body mass index (BMI) range 18 to 34 kg/m^2. The volunteer’s weight must be greater than 50 kg.
3. Free from any clinically significant abnormality on the basis of medical history, vital signs, physical examination, 12-lead electrocardiogram (ECG), echocardiography, ophthalmologic examinations and tests, and laboratory evaluations at screening and admission, as judged by the investigator.
4. Ability to understand and the willingness to provide informed consent for participation in the study.
5. Ability and willingness, as judged by the investigator, to comply with all study requirements, including, but not limited to:
a. Clinic confinement for at least 10 hours before, during, and 48 hours after last administration (for SAD) or 9 Days (for MAD) of the study material, where subject will be asked to remain awake/conscious for the first 4 hours after drug administration
b. Refraining from use of the following, before drug administration and until at least after the last study visit:
i. prescription medicine from 14 days prior,
ii. over-the-counter (OTC) products (eg, paracetamol may be used up to 1 day before the first administration of IP/placebo) from 7 days prior,
iii. natural health products from 7 days prior,
iv. food containing poppy seeds within 24 hours prior,
v. food or beverages containing xanthine derivatives or xanthine-related compounds from 48 hours prior,
vi. energy drinks from 48 hours prior,
vii. food or beverages containing grapefruit, starfruit, pomegranate, pineapple, or pomelo from 7 days prior, and
viii. alcohol-based products from 24 hours prior.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria: subjects will be excluded from study enrollment if they meet any of the following criteria.
1. Any known, documented, or suspected history of:
a. schizophrenia or other psychotic illness, or diagnosis of schizophrenia in a first-degree relative.
b. alcohol or substance abuse within the last 2 years before screening or positive test result(s) for alcohol and or drugs of abuse at screening or on Day -1 (ie, Check-in).
c. Regular alcohol consumption greater than 21 units per week (1 unit = half pint beer, 25 mL of 40% spirit, or a 125-mL glass of wine).
2. Use of nicotine or nicotine-containing products during participation on the study.
3. Limited caffeine consumption from natural (ie, coffee, tea, and chocolate) or synthetic sources (ie, products to promote arousal, alertness, energy, and elevated mood) to no more than 2 units per day (1 unit = 120 mg of caffeine).
4. Any known, documented, or suspected hypersensitivity to cannabinoids or any of the excipients of EHP-101 Liquid.
5. Use of cannabis or cannabinoid-based medications (within 30 days or 5 times the half-life of the study drug [whichever is longer] prior to study entry).
6. Abnormal screening 12-lead ECG interpreted by the investigator to be clinically significant.
7. Clinical laboratory abnormalities as follows (Grades from National Cancer Institute Common Terminology Criteria for AE [NCI CTCAE] version 5.0):
a. Cardiac troponin I, Grade greater than 1
b. Cardiac troponin T, Grade greater than 1
8. Presence of ophthalmologic abnormalities at baseline.
9. Male subjects who are not surgically sterilized and female subjects of childbearing potential who are not using a highly effective method of contraception (failure rate of less than 1% per year when used consistently and correctly: hormonal contraception or an intrauterine device), as judged by the investigator, and who do not consent i) to use a combined barrier method of contraception such as a diaphragm or male partner use of a condom and ii) to remain on a highly effective method of contraception while receiving study intervention during the study and for at least 30 days after the end of study treatment. Examples of highly effective methods of contraception are located in Appendix 1 of the attachment.
Note: Male subjects who are not surgically sterilized are required to use condoms in combination with partner use of a highly effective method of contraception (where a partner is a female of childbearing potential). Total abstinence, in accordance with the usual lifestyle of the subject, is also acceptable.
10. Female subjects who are pregnant, lactating, or planning pregnancy during the course of the study and for 12 weeks thereafter.
11. Male subjects unwilling to abstain from sperm donation during the study and for 12 weeks thereafter.
12. Any evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV types 1 and 2) infection.
Note 1: If hepatitis B and hepatitis C results are greater than or equal to 1 month or not available in the medical history, then this must be confirmed by baseline test result obtained during screening.
Note 2: If no significant hepatotoxicity is observed during Part 1 (SAD), relaxation of this exclusion criterion for Part 2 (MAD) will be considered for subjects with no detectable/low viral load (HBV DNA titer less than 1000 cps/mL or 200 IU/mL; HIV RNA less than 75 cps/mL), or cured hepatitis C (negative HCV RNA test) and who qualify with adequate hepatic function.
13. Subjects who have received an Investigational Product within the 12 weeks before the screening visit.
14. Blood donation or loss (eg, greater than or equal to 400 mL) within 3 months before enrollment and unwilling to abstain from blood donation during the study.
15. Significant disease or disorder, which, in the opinion of the investigator or other staff who is directly involved in the study, may either put the subject at risk because of participation in the study or interfere with the subject's ability to participate in the study.
16. Intake of any metabolic enzyme–affecting drugs from 30 days prior to Day -1 (ie, Check-in).
17. Vaccination within 30 days prior to enrollment.

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)
Allocation involves contacting the holder of the allocation schedule who is the off-site pharmacist with no contact to participants
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
Statistical Analysis will be performed using SAS v9.3 (SAS Institute, Cary, USA).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11458 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 23478 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 300172 0
Commercial sector/Industry
Name [1] 300172 0
Emerald Health Pharmaceuticals Australia Pty Ltd
Address [1] 300172 0
58 Gipps Street,
Collingwood, VIC 3066
Country [1] 300172 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Emerald Health Pharmaceuticals Australia Pty Ltd
Address
58 Gipps Street,
Collingwood, VIC 3066
Country
Australia
Secondary sponsor category [1] 299818 0
None
Name [1] 299818 0
Address [1] 299818 0
Country [1] 299818 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301004 0
Alfred Hospital Human Research Ethics Committee (EC00315)
Ethics committee address [1] 301004 0
The Alfred Hospital,
55 Commercial Road,
Melbourne VIC 3004
Ethics committee country [1] 301004 0
Australia
Date submitted for ethics approval [1] 301004 0
23/07/2018
Approval date [1] 301004 0
Ethics approval number [1] 301004 0

Summary
Brief summary
This research project is being conducted to investigate the safety, tolerability, and pharmacokinetics of single ascending dose and multiple ascending dose of oral EHP-101 when administered in healthy adult subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85566 0
Dr Ben Snyder
Address 85566 0
Nucleus Network
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004.
Country 85566 0
Australia
Phone 85566 0
+61 (0)3 9076 8960
Fax 85566 0
Email 85566 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 85567 0
Mr Stuart Gribble
Address 85567 0
Nucleus Network,
Level 5, Burnet Tower, AMREP Precinct,
89 Commercial Road,
Melbourne VIC 3004.
Country 85567 0
Australia
Phone 85567 0
+61 (0)3 8535 4808
Fax 85567 0
Email 85567 0
s.gribble@nucleusnetwork.com.au
Contact person for scientific queries
Name 85568 0
Dr David Fuller
Address 85568 0
INC Research/Inventiv Health,
Suite 1, Level 2, 924 Pacific Highway,
Gordon NSW 2027.
Country 85568 0
Australia
Phone 85568 0
+61 (0)2 8437 9238
Fax 85568 0
Email 85568 0
david.fuller@syneoshealth.com

No data has been provided for results reporting
Summary results
Not applicable