Trial Review

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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
2/02/2022
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 18-30) 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, an antioxidant (ascorbic acid) 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), ascorbic acid (0.1% w/v) and BAK (0.1% w/v).

Arm 2 (low dose): levodopa (1.2 micromoles/ 0.2 mg), carbidopa (0.3 micromoles/ 0.05 mg), ascorbic acid (0.1% w/v) 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) and ascorbic acid (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 a follow-up measure at 4 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. Participants will complete an ocular surface disease index (OSDI) questionnaire to determine if any ocular irritation is experienced. Tear film osmolarity will be assessed using the TearLab Osmolarity System (TearLab, California, USA). Corneal epithelial integrity will be evaluated using the ocular surface stain sodium fluorescein. Staining will be graded on a 0-5 scale using the Modified Oxford Scale. Sodium fluorescein will also be used to assess tear film breakup time during slit-lamp examination.
Timepoint [2] 325754 0
Primary outcome measures will be assessed at baseline, 4 weeks (primary end point), as well as a follow-up measure at 4 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)). To screen for potential retinal pathologies, fundus photography will be undertaken (Zeiss Clarus 500, Heidelberg Engineering, Heidelberg, Germany).
Timepoint [3] 325755 0
Primary outcome measures will be assessed at baseline, 4 weeks (primary end point), as well as a follow-up measure at 4 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 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. Participants will complete an ocular surface disease index (OSDI) questionnaire to determine if any ocular irritation is experienced. Tear film osmolarity will be assessed using the TearLab Osmolarity System (TearLab, California, USA). Corneal epithelial integrity will be evaluated using the ocular surface stain sodium fluorescein. Staining will be graded on a 0-5 scale using the Modified Oxford Scale. Sodium fluorescein will also be used to assess tear film breakup time during slit-lamp examination.
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)). To screen for potential retinal pathologies, fundus photography will be undertaken (Zeiss Clarus 500, Heidelberg Engineering, Heidelberg, Germany).
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 18-30.
• 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 -5.0 to +3.0 Dioptres (Spherical Equivalent).
• Not be undertaking treatment to inhibit the progression of myopia (including spectacle wear) for at least 12 weeks prior to enrolment. Optical correction for a refractive error is allowed, although contact lenses cannot be worn during the trial period.
Minimum age
18 Years
Maximum age
30 Years
Sex
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
Completed
Date of first participant enrolment
Anticipated
1/12/2020
Actual
1/04/2021
Date of last participant enrolment
Anticipated
Actual
1/06/2021
Date of last data collection
Anticipated
Actual
8/12/2021
Sample size
Target
30
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
ACT

Funding & Sponsors
Funding source category [1] 306937 0
University
Name [1] 306937 0
University of Canberra
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
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
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
[email protected]
Contact person for public queries
Name 105967 0
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
[email protected]
Contact person for scientific queries
Name 105968 0
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
[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


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
SourceTitleYear of PublicationDOI
EmbaseThe safety and tolerability of levodopa eye drops for the treatment of ocular disorders: A randomized first-in-human study.2022https://dx.doi.org/10.1111/cts.13392
N.B. These documents automatically identified may not have been verified by the study sponsor.