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Trial registered on ANZCTR


Registration number
ACTRN12618001390279
Ethics application status
Approved
Date submitted
14/08/2018
Date registered
20/08/2018
Date last updated
2/12/2019
Date data sharing statement initially provided
4/03/2019
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:
Systemic Sclerosis 309251 0
Multiple Sclerosis 308905 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)
7 cohorts of healthy volunteers dosed with single doses of oral EHP-101 liquid (7 planned dose levels from 0.91 to 200 mg), or placebo, and additional cohort (8) with one single dose of oral EHP-101 or placebo dosed under fasted and fed condition.
Participants will be confined to the Study Unit from Day -1 and discharged following collection of the 48 hour post dose assessments (Day 3). Total duration of participant involvement in Part 1 is 31 days from Day -1 admission to Day 30 End of Study assessments, with 4 days of clinic confinement.

Part 2 - Multiple Ascending Dose (MAD)
4 cohorts of healthy volunteers dosed with multiple doses (once or twice daily for a period of 7 days) of oral EHP-101 liquid (4 dose levels), or placebo. Participants will be confined to the Study Unit from Day -1 and discharged on Day 9. Total duration of participant involvement in Part 2 is 31 days from Day -1 admission to Day 30 End of Study assessments, with 10 days of clinic confinement.
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 were administered treatment under supervision by qualified staff in clinical confinement. Drug administration compliance and accountability was 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] 307015 0
To determine the safety and tolerability of oral EHP-101 when administered as a multiple ascending dose (MAD) to healthy subjects once or twice 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 assessment; cardiac telemetry; ECG; echocardiography; troponin I levels; and any other clinical laboratory parameter abnormalities after once or twice daily oral dosing of EHP-101 liquid over 7 days.
Timepoint [1] 307015 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] 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 assessment; cardiac telemetry; ECG; echocardiography; troponin I levels; and any other clinical laboratory parameter abnormalities after a single oral dosing of EHP-101 liquid.
Timepoint [2] 306797 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] 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 levels of proteins will be determined in selected cohorts. This screening will allow for selection of biomarkers for additional ELISA determination which may include but not be limited to 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 [1] 350705 0
PD samples will be collected for serum analysis during the treatment period at:
Pre-dose (less than or equal to 2 hours), 6, 24, 48, and 72 hours post-dose (Part 1, 5 time points) for single ascending dose.
Pre-dose (less than or equal to 2 hours), 6, 24, 48 hours and 7 days post-dose (Part 2, 5 time points) for multiple ascending doses.
PD collection timepoints for Food Effect evaluation for both fasting and fed conditions are the same as those for Part 1, single ascending dose.
Secondary outcome [2] 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 [2] 349675 0
PK samples will be collected for plasma analysis during the treatment period at:
Pre-dose (less than or equal to 2 hours), 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 1, 21 time points) for single ascending dose.
Pre-dose (less than or equal to 2 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 14*, 15*, 16 (Days 1 and 7), 24, 48, 72, 96, 120 hours and 30 days post-dose (Part 2, 31 time points) for multiple ascending doses.
*in the event that doses are administered twice a day, samples at 14 and 15 hours post dose will also be collected.
Secondary outcome [3] 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 [3] 350362 0
PK samples will be collected for plasma analysis during the treatment period at:
Pre-dose (less than or equal to 2 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 16, 24, 48, and 72 hours (Period 1, 15 time points) for fasting condition.
Pre-dose (less than or equal to 2 hours), 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 (Period 2, 21 time points) for fed condition.

Eligibility
Key inclusion 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.
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. Cardiac Troponin I level below the upper limit of normal, as defined by the manufacturer.
5. Ability to understand and the willingness to provide informed consent for participation in the study.
6. Ability and willingness, as judged by the Investigator, to comply with all study requirements.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion 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.
c) Regular alcohol consumption greater than 21 units per week
2. Use of nicotine or nicotine-containing products during participation in the study.
3. Caffeine consumption is limited to no more than 2 units per day.
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.
6. Abnormal screening 12-lead ECG interpreted by the Investigator to be clinically significant.
7. Presence of ophthalmologic abnormalities at baseline, specifically known closed angles, previous laser iridotomy, or severe hypermetropic diagnosis.
8. Male subjects who are not surgically sterilized and who do not agree to use condoms in combination with partner use of a highly effective method of contraception. Female subjects of childbearing potential who are not using a highly effective method of contraception, as judged by the Investigator, and who do not consent: i) to use a combined barrier method of contraception and ii) to remain on a highly effective method of contraception while receiving study intervention during the study and for at least 90 days after the end of study treatment.
9. Female subjects who are pregnant, lactating, or planning pregnancy during the course of the study and for 12 weeks thereafter.
10. Male subjects unwilling to abstain from sperm donation during the study and for 12 weeks thereafter.
11. Any evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV types 1 and 2) infection.
12. Subjects who have received an IP within the 12 weeks before the screening visit.
13. 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.
14. 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.
15. Intake of any metabolic enzyme-affecting drugs from 30 days prior to Day -1 (ie, Check-in).
16. 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
Completed
Date of first participant enrolment
Anticipated
6/09/2018
Actual
26/09/2018
Date of last participant enrolment
Anticipated
13/05/2019
Actual
13/07/2019
Date of last data collection
Anticipated
12/06/2019
Actual
11/08/2019
Sample size
Target
104
Accrual to date
Final
104
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
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
Approved
Ethics committee name [1] 301004 0
Alfred Hospital Human Research Ethics Committee (EC00315)
Ethics committee address [1] 301004 0
Ethics committee country [1] 301004 0
Australia
Date submitted for ethics approval [1] 301004 0
23/07/2018
Approval date [1] 301004 0
07/09/2018
Ethics approval number [1] 301004 0
434-18

Summary
Brief summary
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
Jasmine Panthaki
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 9089 8247
Fax 85567 0
Email 85567 0
j.panthaki@nucleusnetwork.com.au
Contact person for scientific queries
Name 85568 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is a Phase 1 study, only aggregate data may be posted/published.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.