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Trial registered on ANZCTR


Registration number
ACTRN12622000971730
Ethics application status
Approved
Date submitted
13/05/2022
Date registered
8/07/2022
Date last updated
7/04/2024
Date data sharing statement initially provided
8/07/2022
Date results information initially provided
7/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the Safety, Tolerability, and Pharmacokinetics of SBI-100 Ophthalmic Emulsion in Healthy Adult Participants
Scientific title
A Phase 1 Randomised, Double-Masked, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SBI-100 Ophthalmic Emulsion in Healthy Adult Participants
Secondary ID [1] 306692 0
SBI-100-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glaucoma 325645 0
Condition category
Condition code
Eye 323713 323713 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SBI-100 Ophthalmic Emulsion or placebo will be administered as a single approximately 35 µL drop unilaterally to the study eye only, using a masked, Sponsor-approved dropper bottle. The participants will check in to the clinic where the drug will be dispensed and remained confined to the Clinical Research Unit (CRU) until the discharge. The participants in SAD cohort will be confined to CRU for 2 days and those in MAD cohort will be in CRU for a period of 7 days. The strategies used to monitor adherence will be supervised dosing.
The study consists of two parts:
Part A- Single Ascending dose: 3 cohorts of 8 participants randomized 6 (Study drug) and 2(Placebo)
Cohort A1: 1 single dose in right eye of 5.0 mg/mL (0.50%) of study drug or Placebo
Cohort A2: 1 single dose in right eye of 10.0 mg/mL (1.0%) of study drug or Placebo
Cohort A3: 1 single dose in right eye of 20.0 mg/mL (2.0%) of study drug or Placebo
Dose escalation will proceed after review of safety information and approval by the SRC. Part B will commence once the safety information is available for at least 6-8 participants from Cohort A1 and A2 of Part A. The Participants in Part A are distinct from the participants of Part B.

Part B- Multiple Ascending Dose: The MAD part of the study will assess the safety and tolerability of study drug in healthy adult participants at 3 escalating cohorts with 8 participants each where 6 will receive study drug and 2 placebo in a sequential dose cohort manner.
Cohort B1: Twice daily in right eye of 5.0 mg/mL (0.50%) with study drug or placebo for 5 days
Cohort B2: Twice daily in right eye of 10.0 mg/mL (1.0%) with study drug or placebo for 5 days
Cohort B3: Twice daily in right eye of 20.0 mg/mL (2.0%) with study drug or placebo for 5 days
Sequential dose cohorts of SBI-100 Ophthalmic Emulsion (with placebo-control) are planned. All cohorts will consist of 8 participants (6 participants randomised to receive SBI-100 Ophthalmic Emulsion and 2 participants randomised to receive placebo).

Dose escalations will proceed after the review of available safety information and approval by the safety Review committee (SRC).
Intervention code [1] 323140 0
Treatment: Drugs
Comparator / control treatment
Placebo is identical in appearances. It is considered as vehicle consisting of excipients like ophthalmic emulsion contains sesame oil, glycerin, polysorbate 80, carbomer 980 (carbopol), Poloxamer 407, Tocophersolan (tocopherol polyethylene glycol succinate), and water same IP with no active active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 330765 0
To establish the safety and tolerability of single and multiple ascending doses of SBI-100 Ophthalmic Emulsion relative to placebo as assessed by changes noted in ocular assessment in the study eye,
Ocular assessments including a complete opthalmic exam from the front of the eye to the back of the eye with dilation for proper visualization. A baseline will assess the current structure noting the grading and severity, subsequent assessment will note any changes from baseline. Imaging of OCT and retinography will be performed to complement the complete ophthalmic exam and provide detailed visualization of changes to structure from baseline.
Timepoint [1] 330765 0
Screening to end of study (predose and different time points of the study till day 20 post-dose).
Primary outcome [2] 330767 0
To establish the safety and tolerability of single and Multiple ascending doses of SBI-100 Ophthalmic Emulsion relative to placebo in healthy participants by vital signs, clinical laboratory tests, safety labs, ECG and AEs.
Adverse events will be assessed by the symptom focused physical examination and clinical examination of ocular symptoms through complete Ophthalmic examination and participant reports for any change to until follow-up/End of study.
Vital signs that are assessed include blood pressure (BP), Heart rate, Respiratory rate and Temperature. BP will be assessed using a sphygmomanometer and tympanic temperature will be recorded. Clinical laboratory tests and safety labs will use both blood and urine samples.
Timepoint [2] 330767 0
Adverse events will be collected from screening, daily during confinement and at least once a week until resolution, until end of study or up to a 30 day follow up period. Lab tests will be collected from baseline until End of study at least once a day.
Secondary outcome [1] 407492 0
To evaluate the pharmacokinetics (PK) of SBI-100 Ophthalmic Emulsion following a single and multiple dose SBI-100 Ophthalmic Emulsion relative to placebo. The parameters assessed are AUC, Cmax, Tmax etc.
Timepoint [1] 407492 0
During Part A of the study, blood sampling for PK analysis will occur pre-dose (within 2 hours of IP administration), and post-dose at 5 minutes (± 1 minute), 15 minutes (± 2 minutes), 30 minutes (± 5 minutes), 1, 2, 4, 6, 8, and 12 hours (± 15 minutes) and 24 hours (± 60 minutes). An additional PK sample will also be collected at any time during the EOS/ Early Termination (ET) visit. During Part A of the study the end of study visit will occur within 20 days post-dose, or at any time prior to this if the participant withdraws from the study (Early Termination (ET) visit).

During Part B of the study,
Day 1 blood sampling for PK will occur pre-dose (within 15mins prior to IP administration), and after the morning dose of IP at 5 minutes, 15 minutes, 30 minutes, and 1, 2, 4, 6, 8 hours, and at 12 hours. The 12-hour PK blood sample is to be taken before the evening dose of IP; morning and evening doses should be separated by approximately 12 hours.
On Days 2 to 4, blood samples will be drawn within 15 minutes before administration of the morning and evening doses of IP.
On Day 5, blood sampling for PK analysis will occur pre-dose (15 minutes prior to morning dose of IP administration), at 5 minutes , 15 minutes, 30 minutes, and 1, 2, 4, 6, 8 hours, and at 12 hours after the morning dose of IP. The 12-hour PK blood sample is to be taken before the evening dose of IP.
On Day 6, blood sampling for PK analysis will occur at 12 hours and 24 hours after the last dose of IP on Day 5 . A PK sample will be collected before discharge on Day 7 at 36 hours after the last of IP on Day 5 . A PK sample will also be collected at any time during EOS/ET visit. Day 30 will be end of study for Part B
Secondary outcome [2] 407493 0
To evaluate the effects on intraocular pressure (IOP) of SBI-100 Ophthalmic Emulsion following a single and multiple dose SBI-100 Ophthalmic Emulsion relative to placebo.
IOP will be measured using iCare® ic200 tonometer.
Timepoint [2] 407493 0
Screening IOP will be assessed anytime on Screening day and will be re assessed on Day 1 between 6:30 and 10:30 am for eligibility purposes. IOP will then be measured at 1, 2, 4, 8, and 12 hours post-dose (all ± 20 minutes), at 24 hours post-dose (± 30 minutes), and anytime at the EOS/ET visit. ET visit is day 4 for Part A and day 10 for Part B cohorts.

Eligibility
Key inclusion criteria
1. Male or female, 18 to 60 years of age at Screening.
2. Body mass index (BMI) (greater than or equal to) 18.0 and (less than or equal to) 32.0 kg/m2 and weighs at least 50 kg at Screening.
3. Medically healthy based on medical history, physical examination, vital signs, ECGs, or laboratory tests, prior to day 1, in the opinion of the Investigator/designee would not interfere with the study.
4. Habitual visual acuity (VA) at Screening in each eye of 20 /40 or better.
5. Medically healthy eye condition with 2 normal (non-diseased) eyes, with no anatomical ocular abnormalities in the opinion of the Investigator or designee that would interfere with the study (e.g. abnormalities that prevent reliable tonometry).
6. IOP as measured by iCare tonometer in each eye of (greater than or equal to) 10 to (less than or equal to) 21 mmHg at Screening with a difference of (less than or equal to)3 mmHg between each eye.
7. Central corneal thickness in each eye (greater than or equal to) 500 µm and (less than or equal to) 600 µm as measured by optical coherence tomography (OCT) at Screening.
8. To be able to follow contraceptive measures as specified in the protocol.
9. Willing and able to provide voluntary written informed consent prior to any study-related procedures and to comply with all study requirements and instructions.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A participant who meets any of the following exclusion criteria must be excluded from the study:
1. Unable to discontinue contact lens use during study visits including confinement at the study site.
2. Previous ocular surgeries / procedures: such as cataract or refractive surgery (eg, radial keratotomy, photorefractive keratectomy, or laser in situ keratomileusis), and post-YAG laser capsulotomy after cataract surgery, within 12 months of Day 1. Any surgeries or procedures (including laser) to treat glaucoma prior to screening is excluded.
3. Recent (within 3 months prior to Screening) or current evidence of ocular infection or inflammation in either eye (including but not limited to blepharitis, conjunctivitis, uveitis, scleritis or keratitis).
4. Any prior history of herpes simplex keratitis or herpes zoster keratitis in either eye.
5. History of diabetic retinopathy, diabetic macular oedema, or para/central retinal degeneration.
6. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris (eg, irregularly shaped pupil, neurogenic pupil disorder, iris atrophy, etc.).
7. History of cauterisation of the punctum or punctal plug (silicone or collagen) insertion or removal.
8. Use of ophthalmic topical steroids, topical non-steroidal anti-inflammatories, or ocular hypotensive medications within 3 months prior to screening.
9. Use of over-the-counter (OTC) vasoconstrictors/decongestants within past 7 days of Day 1.
10. Conjunctival and/or limbal hyperemia of Grade > 1 on the Efron grading scale.
11. Corneal fluorescein staining Grade > 1 on the Oxford grading scale.
12. Abnormal clinically significant ECG measurements (triplicate ECGs) at Screening or Day 1 (Pre-dose), or any of the following:
a. Clinically significant broadened QRS complex (eg, left bundle branch block in any of the 3 ECG readings)
b. QTcF > 450 msec (males) or > 470 msec (females) as calculated by the average of 3 ECG readings
c. Any ECG abnormality that may compromise a participant’s safety in this study per Investigator’s discretion.
13. Known personal or family history of congenital long QT syndrome or known family history of sudden death.
14. Unstable vital sign(s) or the following values seen at Screening, Day-1, or Day 1 (pre dose) following 5 minutes in the semi-supine position):
a. Systolic blood pressure < 90 mmHg or > 160 mmHg or
b. Diastolic blood pressure < 50 mmHg or > 95 mmHg
c. Pulse rate < 45 beats per minute (bpm) or > 105 bpm
15. Recent (within last 3 years) history of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness.
16. Regular smoker (more than an average of 5 cigarettes per day in the last 3 months) or unable to abstain from smoking (including the use of tobacco or nicotine products and e-cigarettes) from the time of Screening until the EOT visit.
17. Unable to abstain from the use of cannabis and other cannabinoid compounds (other than the study drug) from the time of Screening until after the EOS visit.
18. Known hypersensitivity reaction or allergy to cannabinoids or cannabis or to any component of the SBI-100 formulation including sesame seed/oil allergies or sensitivities.
19. Positive results that indicate an active virological infection at Screening, including for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
20. Received any prescription medication or vaccination (other than contraceptive medication) within 14 days of IP administration, or any OTC, herbal, nutritional or topical medication within 7 days prior to dose administration, and throughout the study. Vitamin administration and up to 2 g paracetamol per day is allowable prior to and during 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)
Allocation is concealed. The allocation will occur via numbered containers per an central randomization by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation) will be generated by the biostatistician and retained for the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
Single Ascending dose (SAD) cohorts: Participants in each cohort will be randomised in a ratio of 6:2 to SBI-100 or placebo. Participants will be screened within 28 days prior to dosing and check into the centre to receive single dose of SBI-100 or placebo on Day 1 and remain in confined Clinical Research Unit (CRU) for Day2. They will then return to the study centre for complete safety assessments at Day 4 (End of Study [EOS]).

Multiple Ascending Dose (MAD)cohorts: Participants in each cohort will be randomised in a ratio of 6:2 to SBI-100 or placebo. Participants will check-in to the clinic on Day -1, receive their first dose on Day 1, remain confined with BID dosing through to Day 5, and be discharged from the CRU on Day 7. They will then return to the study centre for complete safety assessments at Day 10 (EOS). SBI-100 Ophthalmic Emulsion or placebo drops will be administered twice daily (BID) for 5 days in the study eye,
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Part A (single-ascending dose) and Part B (multiple-ascending dose) data will be analysed separately. In general, data will be summarized by dose group, with participants receiving placebo pooled across cohorts. Data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/12/2022
Actual
13/12/2022
Date of last participant enrolment
Anticipated
6/06/2023
Actual
6/06/2023
Date of last data collection
Anticipated
5/07/2023
Actual
6/07/2023
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21976 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 37074 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311024 0
Commercial sector/Industry
Name [1] 311024 0
Skye Biosciences,Inc.
Country [1] 311024 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Skye Biosciences,Inc.
Address
11250 El Camino Real, Suite 100, San Diego, CA, 92130
Country
United States of America
Secondary sponsor category [1] 312346 0
None
Name [1] 312346 0
Address [1] 312346 0
Country [1] 312346 0
Other collaborator category [1] 282212 0
Commercial sector/Industry
Name [1] 282212 0
Novotech(Australia) Pty Limited
Address [1] 282212 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282212 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310570 0
Bellberry Limited
Ethics committee address [1] 310570 0
123 Glen Osmond Road, Eastwood SA 5063, Australia
Ethics committee country [1] 310570 0
Australia
Date submitted for ethics approval [1] 310570 0
09/03/2022
Approval date [1] 310570 0
29/06/2022
Ethics approval number [1] 310570 0
2021-12-1450

Summary
Brief summary
This is a randomised, double-masked, placebo-controlled, single and multiple Ascending dose study to evaluate the safety, tolerability, and pharmacokinetics of SBI-100 Ophthalmic Emulsion in healthy adult participants. The study will enroll 48 healthy volunteers who will receive either study drug or placebo at the stay-in centre where they will be observed for any changes during the course of study period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118126 0
Prof Sepehr Shakib
Address 118126 0
CMAX Clinical Research Pty Ltd, Level 5, 18a North Terrace, Adelaide SA 5000 Australia
Country 118126 0
Australia
Phone 118126 0
+61 411 100 278
Fax 118126 0
Email 118126 0
Sepehr.shakib@cmax.com.au
Contact person for public queries
Name 118127 0
Ms Nolinne Keo
Address 118127 0
Director, Clinical Operations, Skye Bioscience, Inc., 11250 El Camino Real, Suite 100, San Diego, CA, 92130
Country 118127 0
United States of America
Phone 118127 0
+1 858 410 0266
Fax 118127 0
Email 118127 0
nk@skyebioscience.com
Contact person for scientific queries
Name 118128 0
Mr Tu Diep
Address 118128 0
Chief Development Officer, Skye Bioscience, Inc., 11250 El Camino Real, Suite 100, San Diego, CA, 92130
Country 118128 0
United States of America
Phone 118128 0
+1 619 208 7501
Fax 118128 0
Email 118128 0
td@skyebioscience.com

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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