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Trial registered on ANZCTR


Registration number
ACTRN12620001259932
Ethics application status
Approved
Date submitted
13/10/2020
Date registered
24/11/2020
Date last updated
24/11/2020
Date data sharing statement initially provided
24/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerability trial of an eye drop treatment for short sightedness (myopia)
Scientific title
Phase 1 safety and tolerability trial of levodopa eye drops for the treatment of short sightedness (myopia)
Secondary ID [1] 302506 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myopia 319368 0
Condition category
Condition code
Eye 317333 317333 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will be a first-in-human placebo controlled, double-blind randomised clinical trial to assess the safety and tolerability of a levodopa:carbidopa ophthalmic solution in young adults (males, aged 18-25) treated for a period of 4 weeks (28 days). For treatment, this study will follow a paired eye design. Participants will administer the active ophthalmic solution described below to one eye and the placebo solution to the other eye. Participants will be split into two arms (arm 1 - high dose ophthalmic solution, arm 2 – low dose ophthalmic solution). Participants will be randomly assigned to either arm, with which eye to be treated and which to act as a control also randomised.

Formulation
A topical eye drop solution containing levodopa, carbidopa and a preservative (benzalkonium chloride (BAK)) dissolved in a saline solution.

Dose per day (80 microliter administered volume)
Arm 1 (high dose): levodopa (2.4 micromoles/ 0.4 mg), carbidopa (0.6 micromoles/ 0.1 mg) and BAK (0.1% w/v).

Arm 2 (low dose): levodopa (1.2 micromoles/ 0.2 mg), carbidopa (0.3 micromoles/ 0.05 mg) and BAK (0.1% w/v).

Duration
Administered as two drops (80 microliters total) to the corneal surface once per day (morning) for a period of 4 weeks (28 days).

Mode
Topical eye drops

Adherence
Each participant will keep a diary detailing their daily use of the trial medication. All dropper bottles will also be weighed before commencement and at the end of the treatment period as a measure of adherence.
Intervention code [1] 318798 0
Treatment: Drugs
Comparator / control treatment
This study will follow a paired eye design. Participants will administer the active ophthalmic solution to one eye and the placebo solution to the other eye.

The placebo eye drop solution will contain benzalkonium chloride (BAK, 0.1% w/v) dissolved in a saline solution.
Control group
Placebo

Outcomes
Primary outcome [1] 325375 0
Visual function:

Change in multifocal electroretinogram (mfERG) from baseline to end of study will be used as a non-invasive evaluation of retinal function (VERIS 5.1.5× refractor/camera system, Electro-Diagnostic Imaging Inc., Redwood City, CA, USA). Visual function will also be assessed subjectively through changes in high (>90%) and low (10%) contrast visual acuity (VA, Thomson Test Chart, Thomson Software Solutions, Hatfield UK) from baseline to end of study. Additionally, all participants will undertake a central 30-degree visual field test using Frequency doubling technology (FDT) perimetry (Matrix, Carl Zeiss)
Timepoint [1] 325375 0
Primary outcome measures will be assessed at baseline, 4 weeks (primary end point), as well as follow-up measures at 3 and 6 months after cessation of treatment.
Primary outcome [2] 325754 0
Ocular surface tolerability:

Clinical assessment of the tear film, evaluation of conjunctival hyperaemia/erythema and localised corneal epithelial desiccation will be used to assess ocular surface tolerability. Tear film osmolarity will be assessed using the TearLab Osmolarity System (TearLab, California, USA) and non-invasive tear break up time will be evaluated with the Medmont Topographer (Medmont International PTY Victoria, Australia). Corneal epithelial integrity will be evaluated using two ocular surface stains (sodium fluorescein and lissamine green). Staining will be graded on a 0-5 scale using the Modified Oxford Scale.
Timepoint [2] 325754 0
Primary outcome measures will be assessed at baseline, 4 weeks (primary end point), as well as follow-up measures at 3 and 6 months after cessation of treatment.
Primary outcome [3] 325755 0
Ocular health:

Change in retinal and choroidal thickness from baseline to end of study will be measured using optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Sub-foveal choroidal thickness measurements will also be obtained using enhanced depth imaging spectral-domain OCT (EDI-SD OCT). Intraocular pressure (IOP) will also be measured at all visits (rebound tonometry (iCare ic100)).
Timepoint [3] 325755 0
Primary outcome measures will be assessed at baseline, 4 weeks (primary end point), as well as follow-up measures at 3 and 6 months after cessation of treatment.
Secondary outcome [1] 387710 0
Visual function:

Visual function will also be assessed subjectively through changes in high (>90%) and low (10%) contrast visual acuity (VA, Thomson Test Chart, Thomson Software Solutions, Hatfield UK) from baseline to end of study. Additionally, all participants will undertake a central 30-degree visual field test using Frequency doubling technology (FDT) perimetry (Matrix, Carl Zeiss)
Timepoint [1] 387710 0
The secondary 'subset measures' will be carried out at the end of weeks 1, 2 and 3.
Secondary outcome [2] 389009 0
Ocular health:

Change in retinal and choroidal thickness from baseline to end of study will be measured using optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Sub-foveal choroidal thickness measurements will also be obtained using enhanced depth imaging spectral-domain OCT (EDI-SD OCT). Intraocular pressure (IOP) will also be measured at all visits (rebound tonometry (iCare ic100)).
Timepoint [2] 389009 0
The secondary 'subset measures' will be carried out at the end of weeks 1, 2 and 3.
Secondary outcome [3] 389011 0
Ocular health:

Change in retinal and choroidal thickness from baseline to end of study will be measured using optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Sub-foveal choroidal thickness measurements will also be obtained using enhanced depth imaging spectral-domain OCT (EDI-SD OCT). Intraocular pressure (IOP) will also be measured at all visits (rebound tonometry (iCare ic100)).
Timepoint [3] 389011 0
The secondary 'subset measures' will be carried out at the end of weeks 1, 2 and 3.

Eligibility
Key inclusion criteria
• Males aged 18-25.
• Visual acuity, measured in each eye without cycloplegia, of 0.1 logMAR or 6/7.5 Snellen equivalent.
• Cycloplegic auto-refraction in the range of -0.5 to +1.0 Dioptres (Spherical Equivalent).
• No current myopia treatment (including spectacle wear) for at least 12 weeks prior to enrolment.
Minimum age
18 Years
Maximum age
25 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Evidence of anterior/posterior segment ocular disease/disorder.
• Currently undergoing visual therapy.
• Treatment with topical atropine or any other topical therapeutic solution (except over-the-counter artificial tears) within the past 12 weeks.
• Current treatment with monoamine oxidase inhibitors, antihypertensives, anti-depressants, phenothiazines (antipsychotics), butyrophenones (dopamine agonists), risperidones and isoniazids (antipsychotics).
• Prior intraocular or refractive surgery.
• History of narrow angle glaucoma or evidence of narrow anterior chamber angles on ophthalmic exam.
• History of dystonic reactions (involuntary muscle contraction).
• Current requirement to take oral iron supplements including multivitamins containing iron.
• Current treatment with medication for attention deficient hyperactivity disorder (ADHD).
• Known gastrointestinal, liver, or renal disease/impairment.
• History of melanoma or undiagnosed suspicious skin lesions.
• Allergy and/or hypersensitivity to Levodopa or Carbidopa.
• Known psychological problems.
• Prior Levodopa or Levodopa/Carbidopa treatment.
• Prior bronchial asthma or pulmonary disease.
• Physician prescribed diet high in protein.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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)
ACT

Funding & Sponsors
Funding source category [1] 306937 0
University
Name [1] 306937 0
University of Canberra
Address [1] 306937 0
11 Kirinari St,
Bruce,
ACT,
2617
Country [1] 306937 0
Australia
Primary sponsor type
University
Name
University of Canberra
Address
11 Kirinari St,
Bruce,
ACT,
2617
Country
Australia
Secondary sponsor category [1] 307497 0
None
Name [1] 307497 0
Address [1] 307497 0
Country [1] 307497 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307081 0
University of Canberra Human Ethics Committee
Ethics committee address [1] 307081 0
University of Canberra,
11 Kirinari St,
Bruce,
ACT,
2617
Ethics committee country [1] 307081 0
Australia
Date submitted for ethics approval [1] 307081 0
Approval date [1] 307081 0
19/05/2020
Ethics approval number [1] 307081 0
HREC-0406

Summary
Brief summary
This will be a first-in-human safety and tolerability trial of a novel ophthalmic solution for the treatment of the visual disorder myopia (short-sightedness). Myopia has been hypothesised to be driven by a reduction in dopamine levels within the eye. Over the past five decades, levodopa (the precursor to dopamine) has been the primary treatment for neurological disorders involving the dysregulation of the dopaminergic system, such as Parkinson’s disease. Before we can examine the efficacy of this compound at inhibiting myopia, this study will assess the safety and tolerability of levodopa as a reformulated eye drop solution.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105966 0
A/Prof Regan Ashby
Address 105966 0
University of Canberra,
Faculty of Science and Technology,
Centre for Research into Therapeutic Solutions
11 Kirinari St,
Bruce,
ACT,
2617
Country 105966 0
Australia
Phone 105966 0
+61 2 62012088
Fax 105966 0
Email 105966 0
regan.ashby@canberra.edu.au
Contact person for public queries
Name 105967 0
Ms Kate Thomson
Address 105967 0
University of Canberra,
Faculty of Science and Technology,
Centre for Research into Therapeutic Solutions
11 Kirinari St,
Bruce,
ACT,
2617
Country 105967 0
Australia
Phone 105967 0
+61 2 62012088
Fax 105967 0
Email 105967 0
kate.thomson@canberra.edu.au
Contact person for scientific queries
Name 105968 0
A/Prof Regan Ashby
Address 105968 0
University of Canberra,
Faculty of Science and Technology,
Centre for Research into Therapeutic Solutions
11 Kirinari St,
Bruce,
ACT,
2617
Country 105968 0
Australia
Phone 105968 0
+61 2 62012088
Fax 105968 0
Email 105968 0
regan.ashby@canberra.edu.au

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 other documents available
Summary results
No Results