Mydriasis
Conditions
Keywords
Mydriasis, Mydriatics, Phenylephrine, Tropicamide
Brief summary
The objective of this study is to explore pharmacodynamic effects and safety of IMP 08P2002F0 for dilation of the pupil, a solution combining two mydriatic agents tropicamide and phenylephrine hydrochloride at the concentrations of 0.34% and 2.5% respectively, versus Mydriasert®
Interventions
DRUGIMP 08P2002F0
Fixed combination of 0.34 % tropicamide and 2.5 % phenylephrine Hydrochloride (HCl) Eye drop Solution.
DRUGMydriasert® insert
0.28 mg tropicamide and 5.4 mg phenylephrine hydrochloride
Sponsors
Unither Pharmaceuticals, France
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Open-label, Observer-masked, active-controlled, randomized cross-over phase I/II study in healthy volunteers.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers of both genders, aged ≥18 at the time of signing the informed consent. * Healthy volunteers are declared healthy based on medical history, physical examination, ophthalmological examination, Electrocardiogram (ECG), within the stated normal range; a participant with a clinical abnormality or laboratory parameter(s) outside the reference range may be included if the investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or interpretation.. 3\. Females who participate in the study, that are at reproductive age agree to undergo pregnancy tests and to use a highly effective birth control method during the study.
Exclusion criteria
* Hypersensitivity to the active substances or to the excipients or related class of the medicinal product. Serious hypersensitivity reactions include angioedema, anaphylaxis and exfoliative skin conditions including Stevens-Johnson syndrome. * Clinically significant illness or surgery within four weeks prior IMP administration. * Clinically significant ECG abnormalities or vital sign abnormalities (seated systolic blood pressure \< 90 or \>140 mmHg, seated diastolic blood pressure \< 50 or \> 90 mmHg or heart rate less than 50 or over 100 bpm) at screening. History or presence of any clinically significant cardiovascular, pulmonary, hepatobiliary, renal, haematological, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, malignant disease or eye disorders as glaucoma or a family history of glaucoma. * Clinically significant abnormal laboratory values. * Unwilling to discontinue use of contact lenses on the day of a treatment visit. * Current active eye disease (i.e. any disease for which topical or systemic ophthalmic medication is necessary). In case of historical eye disease, topical or systemic ophthalmic medication should have been stopped for at least one month before the study. * Pupillary abnormalities (irregular, very dark iris, iris synechiae, eye movement disorder (e.g. Nystagmus, etc.), dacryocystitis and all other pathologies of tears drainage system. * Use of any ophthalmic medication except unpreserved artificial tears on the day of a treatment visit. * History of inflammatory ocular disease (e.g. iritis, uveitis, herpetic keratitis). * History of ocular trauma, infection or inflammation within the last 3 months. * Ocular surgery or laser treatment of any kind in the study eye within 3 months. * Irregularly-shaped pupil secondary to ocular trauma, intraocular surgery or congenital defect. * History of neurogenic pupil disorder (e.g. Horner's syndrome, third cranial nerve palsy, Adie's pupil, Argyl Robertson syndrome, etc.). * History of iris surgery of any kind (e.g. iridotomy, iridectomy, coreoplasty). * History of previous corneal surgery; iris atrophy, traumatic mydriasis or angle recession, chronic or acute uveitis. * Corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis). Pseudoexfoliation, exfoliative syndrome. * History of closed-angle glaucoma. * Subjects with narrow angle prone to glaucoma precipitated by mydriatics * Subject undergoing treatment identified as potentially interacting with the IMP, including antidepressant drugs, beta-blockers, other indirect sympathomimetics, alpha sympathomimetics (oral and/or nasal routes), dopaminergic ergot alkaloids, ergot alkaloid vasoconstrictors, selective MAOI-A, linezolid, and halogenated volatile anesthetics. -. Subject planning to receive an MAOI within 3 weeks following the end of the study. * Subjects who have received non-selective monoamine oxidase inhibitors (MAOIs) within the last 15 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Pupil Diameter at 60 Minutes From the Time of First Dose Versus Baseline, as Measured With Photo (Central Reading) | 60 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Obtain Sufficient Mydriasis | 6 hours post dose | This endpoint represents the time to first achievement of a pupil diameter ≥7.0 mm, analyzed using Kaplan-Meier time-to-event methods. The reported median time corresponds to the time at which 50% of eyes reached this threshold and does not indicate that all eyes had achieved a pupil diameter ≥7.0 mm at that timepoint. While all eyes eventually reached ≥7.0 mm during the observation period (no censored observations), some did so after the 30-minute assessment reported in Outcome Measure 8. |
| Proportion of Eyes Achieving Pupil Diameter of 6.0 mm or Greater | Throughout the 6 hours, at 30 minutes, at 1 hour and 2 hours. | — |
| Proportion of Eyes Achieving Pupil Diameter of 7.0 mm | Throughout the 6 hours, at 30 minutes, at 1 hour and 2 hours. | — |
| Time From Baseline to Maximal Pupil Dilation | 6 hours post dose | — |
| Change in Pupil Diameter at Other Timepoints | At 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1 hour and 15 minutes, 1 hour and 30 minutes, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 4 hours and 30 minutes, 5 hours, 6 hours. | — |
| Pupil Size | At baseline, 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1 hour and 15 minutes, 1 hour and 30 minutes, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 4 hours and 30 minutes, 5 hours, 6 hours. | — |
| Distribution of Pupil Diameters | At 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1 hour and 15 minutes, 1 hour and 30 minutes, 2 hours, 2 hours and 30 minutes, 3 hours, 3 hours and 30 minutes, 4 hours, 4 hours and 30 minutes, 5 hours, 6 hours | — |
| Subject Ocular Discomfort | At 10 minutes, 30 minutes, 60 minutes, 1 hour and 30 minutes, 2 hours, and 6 hours post-administration. | Healthy volunteers will be asked to respond regarding the following ocular signs after instillation of the respective IMP: irritation/burning/stinging, eye dryness, foreign body sensation, blurred vision by "yes" or "no" and to assess the severity by grading 0 = none, 1 = slight, 2 = moderate, 3 = severe, if sign(s) were noted with "yes" A higher score means a worse result. |
| Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | Throughout the 6 hours, at 3 hours, 4 hours, 5 hours, 6 hours. | — |
| Percentage of Subjects' Study Eyes Returning to Less Than or Equal to 0.2 mm From Baseline Pupil Diameter | Throughout the 6 hours, at 3 hours, 4 hours, 5 hours, 6 hours. | — |
Countries
Greece
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.75 years STANDARD_DEVIATION 15.341 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
None listed