Healthy Subjects
Conditions
Brief summary
The study evaluate the efficacy, safety and local tolerability of Chloroprocaine 3% ophthalmic gel as compared to matching placebo in healthy subjects.
Detailed description
One hundred and five (105) healthy male and female subjects will be randomised in a 4:1 ratio to receive a single ocular instillation of Chloroprocaine 3% ophthalmic gel or matching placebo (vehicle) (84 subjects will receive chloroprocaine and 21 subjects will receive placebo). The assigned investigational product (3 drops) will be instilled in the right eye of each subject. Administrations will be performed at the clinical centre by the Investigator or his deputy on study day 1. For each administration, the 3 drops will be instilled at a 1 min ± 15 sec interval.
Interventions
DRUGOcular gel
3 drops instilled in the right eye
Sponsors
Sintetica SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Informed consent: Signed written informed consent before inclusion in the study * Sex and age: Healthy men and women, 18 - 55 years inclusive * Body Mass Index: 18.5-30 kg/m2 inclusive * Vital signs: Systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position * Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study * Contraception and fertility: women of child-bearing potential must be using at least one of the following reliable methods of contraception: 1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit; 2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit 3. A male sexual partner who agrees to use a male condom with spermicide 4. A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, urine pregnancy test result must be negative at screening.
Exclusion criteria
* Physical findings: Clinically significant abnormal physical findings which could interfere with the objectives of the study * Visual acuity: Best corrected visual acuity \< 1/10 * Concomitant medications: Medications, including over the counter medications and herbal remedies, systemic opioids and morphine drugs, topical ocular products with anaesthetic action, systemic analgesic drugs, for 2 weeks before study screening * Ophthalmic diseases: Clinically significant ocular disease; eye movement disorder (i.e. nystagmus); dacryocystitis and all others pathologies of tears drainage system; corneal, epithelial, stromal or endothelial, residual or evolutionary disease (including corneal ulceration and superficial punctuate keratitis); history of inflammatory ocular disease (iritis, uveitis, herpetic keratitis), history of ocular traumatism, infection or inflammation within the last 3 months or history of any other ocular disease that may affect the outcome of the study or the subject's safety * Ophthalmic surgery: History of ophthalmic surgical complications (e.g. cystoid macular oedema) in the last 6 months * Diseases: Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, psychiatric or neurological diseases or surgeries that may interfere with the aim of the study * Allergy: Ascertained or presumptive hypersensitivity to the active principle and/or ingredients of investigational products; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study * Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study * Drug, alcohol, caffeine, tobacco: history of drug, alcohol \[greater than 1 drink/day for women and greater than 2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020\], caffeine (greater than 5 cups coffee/tea/day) or tobacco abuse (greater than or equal 10 cigarettes/day) * Alcohol test: positive alcohol breath test at Day 1 * Pregnancy (women only): positive or missing pregnancy test at screening, pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Gaining Full Conjunctival Anesthesia of the Ocular Surface | Day 1 | Number of partecipants gaining full conjunctival anesthesia of the ocular surface, evaluated by conjunctiva pinching (0.3-mm forceps), 5 minutes after administration of Chloroprocaine 3% ophthalmic gel, in comparison to placebo - only study eye (right eye) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Anesthesia - Only Right Eye | Day 1 | Duration of anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye) |
| Visual Acuity (EDTRS Chart) - Both Eyes | Up to day 7 | Visual acuity will be assessed, for all subjects and both eyes using an EDTRS chart (visual acuity is scored with reference to the logarithm of the minimum angle of resolution, an observer who can resolve details as small as 1 minute of visual angle scores LogMAR 0, since the base-10 logarithm of 1 is 0; an observer who can resolve details as small as 2 minutes of visual angle (i.e., reduced acuity) scores LogMAR 0.3, since the base-10 logarithm of 2 is near-approximately 0.3; and so on) |
| Ocular Symptoms | Up to day 7 | The ocular symptoms will be assessed: burning, stinging, itching, foreign body sensation. Scores will be determined using a 100 mm VAS where 0 means no symptoms and 100 means worst possible discomfort. |
| Ocular Signs by Slit Lamp Examination | Up to day 7 | Slit lamp biomicroscopy will be performed for the assessment of the following parameters: conjunctival redness, anterior chamber flare, conjunctival chemosis, eyelid swelling. Presence and severity will be graded according to a 4 point scale, where (0) none, (1) mild, (2) moderate, (3) severe. |
| Time to Anesthesia, Evaluated by Conjunctiva Pinching (0.3-mm Forceps) - Only Study Eye (Right Eye) | Day 1 | Time to anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye) |
| Intraocular Pressure (IOP) - Both Eyes | Up to day 7 | Intraocular pressure will be measured with a slit-lamp mounted Goldmann applanation tonometer. Before each measurement one drop of oxybuprocaine hydrochloride combined with sodium fluorescein will be used for local anaesthesia of the cornea. |
| Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Up to day 7 | Indirect fundus ophthalmoscopy will be performed, for all subjects and both eyes, with the observation at the slit lamp using a +90 diopters Volk lens.The evaluation is performed with a grading scale: 0 None, 1 Mild, 2 Moderate, 3 Severe for each parameters evaluated. |
| Vital Signs (Blood Pressure) | Up to day 7 | Subjects blood pressure will be measured by the Investigator or his/her deputy |
| Vital Signs (Heart Rate) | Up to day 7 | Subjects heart rate will be measured by the Investigator or his/her deputy |
| Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | Up to day 7 | Fluorescein will be used to detect corneal epithelial defects using slit lamp biomicroscopy. As grading scale for corneal damage, the NEI/Industry Workshop guidelines will be used. The cornea will be divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, where 0 means no staining and 3 means maximum staining, with a maximal score of 15. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chloroprocaine Chloroprocaine 3% ocular gel (30 mg/mL), 3 drops instilled at a 1 min ± 15 sec interval.
Ocular gel: 3 drops instilled in the right eye | 84 |
| Placebo Vehicle for chloroprocaine 3% ocular gel, 3 drops instilled at a 1 min ± 15 sec interval.
Ocular gel: 3 drops instilled in the right eye | 21 |
| Total | 105 |
Baseline characteristics
| Characteristic | Chloroprocaine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 10.8 | 38.4 years STANDARD_DEVIATION 10.8 | 37.3 years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 79 Participants | 99 Participants | 20 Participants |
| Region of Enrollment Switzerland | 84 participants | 105 participants | 21 participants |
| Sex: Female, Male Female | 52 Participants | 62 Participants | 10 Participants |
| Sex: Female, Male Male | 32 Participants | 43 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 21 |
| other Total, other adverse events | 27 / 84 | 4 / 21 |
| serious Total, serious adverse events | 0 / 84 | 0 / 21 |
Outcome results
Primary
Number of Participants Gaining Full Conjunctival Anesthesia of the Ocular Surface
Number of partecipants gaining full conjunctival anesthesia of the ocular surface, evaluated by conjunctiva pinching (0.3-mm forceps), 5 minutes after administration of Chloroprocaine 3% ophthalmic gel, in comparison to placebo - only study eye (right eye)
Time frame: Day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chloroprocaine | Number of Participants Gaining Full Conjunctival Anesthesia of the Ocular Surface | 61 Participants |
| Placebo | Number of Participants Gaining Full Conjunctival Anesthesia of the Ocular Surface | 2 Participants |
Secondary
Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes
Fluorescein will be used to detect corneal epithelial defects using slit lamp biomicroscopy. As grading scale for corneal damage, the NEI/Industry Workshop guidelines will be used. The cornea will be divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, where 0 means no staining and 3 means maximum staining, with a maximal score of 15.
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | Screening - right eye | 0 score on a scale | Standard Deviation 0.1 |
| Chloroprocaine | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | follow-up - right eye | 0 score on a scale | Standard Deviation 0.2 |
| Chloroprocaine | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | screening - left eye | 0 score on a scale | Standard Deviation 0.2 |
| Chloroprocaine | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | follow-up - left eye | 0 score on a scale | Standard Deviation 0.1 |
| Placebo | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | follow-up - left eye | 0 score on a scale | Standard Deviation 0.2 |
| Placebo | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | Screening - right eye | 0 score on a scale | Standard Deviation 0 |
| Placebo | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | screening - left eye | 0 score on a scale | Standard Deviation 0 |
| Placebo | Corneal Fluorescein Staining by Slit Lamp Examination - Both Eyes | follow-up - right eye | 0 score on a scale | Standard Deviation 0.2 |
Secondary
Duration of Anesthesia - Only Right Eye
Duration of anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye)
Time frame: Day 1
Population: A total of 105 healthy men and women were planned and enrolled included in the study. Initially, local tolerability and safety was evaluated in the first 20 enrolled subjects . After the first 20 subjects had completed the study, local tolerability and safety data were evaluated and treatment safety was confirmed according to the clinical study protocol specifications. Efficacy, beside local tolerability and safety, was assessed in the 85 subsequent subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chloroprocaine | Duration of Anesthesia - Only Right Eye | 18.3 minutes | Standard Deviation 10 |
| Placebo | Duration of Anesthesia - Only Right Eye | 19.3 minutes | Standard Deviation 14 |
Secondary
Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes
Indirect fundus ophthalmoscopy will be performed, for all subjects and both eyes, with the observation at the slit lamp using a +90 diopters Volk lens.The evaluation is performed with a grading scale: 0 None, 1 Mild, 2 Moderate, 3 Severe for each parameters evaluated.
Time frame: Up to day 7
Population: Initially, safety and local tolerability were evaluated and confirmed in the first 20 enrolled subjects. Then efficacy, beside local tolerability and safety, was assessed in the 85 additional subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in right eye at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in right eye at follow up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in left eye at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in left eye at follow up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in right eye at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in right eye at follow up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in left eye at screening | 0 score on a scale | Standard Deviation 0.1 |
| Chloroprocaine | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in left eye at follow-up | 0 score on a scale | Standard Deviation 0.1 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in left eye at follow-up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in right eye at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in right eye at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in right eye at follow up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in left eye at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in left eye at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Macula, (Peripheral) Retina and Optic Nerve scores in right eye at follow up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Fundus Ophthalmoscopy (Vitreous, Macula, Retina and Optic Nerve Head) With the Slit Lamp - Both Eyes | Vitreous scores in left eye at follow up | 0 score on a scale | Standard Deviation 0 |
Secondary
Intraocular Pressure (IOP) - Both Eyes
Intraocular pressure will be measured with a slit-lamp mounted Goldmann applanation tonometer. Before each measurement one drop of oxybuprocaine hydrochloride combined with sodium fluorescein will be used for local anaesthesia of the cornea.
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Intraocular Pressure (IOP) - Both Eyes | right eye at screening | 12.7 mm Hg | Standard Deviation 2.6 |
| Chloroprocaine | Intraocular Pressure (IOP) - Both Eyes | right eye at follow-up | 12.3 mm Hg | Standard Deviation 2.1 |
| Chloroprocaine | Intraocular Pressure (IOP) - Both Eyes | left eye at screening | 12.5 mm Hg | Standard Deviation 2.3 |
| Chloroprocaine | Intraocular Pressure (IOP) - Both Eyes | left eye at follow-up | 12.4 mm Hg | Standard Deviation 2.2 |
| Placebo | Intraocular Pressure (IOP) - Both Eyes | left eye at follow-up | 12.6 mm Hg | Standard Deviation 2 |
| Placebo | Intraocular Pressure (IOP) - Both Eyes | right eye at screening | 13.2 mm Hg | Standard Deviation 2.5 |
| Placebo | Intraocular Pressure (IOP) - Both Eyes | left eye at screening | 13.5 mm Hg | Standard Deviation 2.2 |
| Placebo | Intraocular Pressure (IOP) - Both Eyes | right eye at follow-up | 12.3 mm Hg | Standard Deviation 2 |
Secondary
Ocular Signs by Slit Lamp Examination
Slit lamp biomicroscopy will be performed for the assessment of the following parameters: conjunctival redness, anterior chamber flare, conjunctival chemosis, eyelid swelling. Presence and severity will be graded according to a 4 point scale, where (0) none, (1) mild, (2) moderate, (3) severe.
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at screening | 0.04 score on a scale | Standard Deviation 0.19 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at pre-dose | 0.02 score on a scale | Standard Deviation 0.15 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at post dose | 0.29 score on a scale | Standard Deviation 0.57 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at follow-up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Anterior chamber flare at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Anterior chamber flare at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Anterior chamber flare post-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Anterior chamber flare follow-up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at post-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at follow-up | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Eyelid swelling at screening | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Eyelid swelling at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Eyelid swelling post-dose | 0 score on a scale | Standard Deviation 0 |
| Chloroprocaine | Ocular Signs by Slit Lamp Examination | Eyelid swelling at follow-up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Eyelid swelling at follow-up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at screening | 0.05 score on a scale | Standard Deviation 0.22 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Eyelid swelling at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at post dose | 0.14 score on a scale | Standard Deviation 0.48 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival redness scores at follow-up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Eyelid swelling post-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Anterior chamber flare at screening | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at post-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Anterior chamber flare at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Eyelid swelling at pre-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Anterior chamber flare post-dose | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Conjunctival chemosis at follow-up | 0 score on a scale | Standard Deviation 0 |
| Placebo | Ocular Signs by Slit Lamp Examination | Anterior chamber flare follow-up | 0 score on a scale | Standard Deviation 0 |
Secondary
Ocular Symptoms
The ocular symptoms will be assessed: burning, stinging, itching, foreign body sensation. Scores will be determined using a 100 mm VAS where 0 means no symptoms and 100 means worst possible discomfort.
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Ocular Symptoms | Itching in right eye at follow-up | 1.35 mm | Standard Deviation 10.8 |
| Chloroprocaine | Ocular Symptoms | burning in right eye at Screening | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | burning in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | burning in right eye at post-dose | 1.17 mm | Standard Deviation 10 |
| Chloroprocaine | Ocular Symptoms | burning in right eye at follow-up | 1.35 mm | Standard Deviation 10.8 |
| Chloroprocaine | Ocular Symptoms | Stinging in right eye at screening | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Stinging in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Stinging in right eye at post-dose | 0.73 mm | Standard Deviation 6.66 |
| Chloroprocaine | Ocular Symptoms | Stinging in right eye at follow-up | 1.88 mm | Standard Deviation 12.51 |
| Chloroprocaine | Ocular Symptoms | Itching in right eye at screening | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Itching in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Itching in right eye at post-dose | 1.17 mm | Standard Deviation 10.05 |
| Chloroprocaine | Ocular Symptoms | Foreign body sensation in right eye at screening | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Foreign body sensation in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Chloroprocaine | Ocular Symptoms | Foreign body sensation in right eye at post-dose | 0.93 mm | Standard Deviation 6.12 |
| Chloroprocaine | Ocular Symptoms | Foreign body sensation in right eye at follow-up | 1.21 mm | Standard Deviation 7.92 |
| Placebo | Ocular Symptoms | Foreign body sensation in right eye at follow-up | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Itching in right eye at follow-up | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Stinging in right eye at follow-up | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | burning in right eye at Screening | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Foreign body sensation in right eye at screening | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | burning in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Itching in right eye at screening | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | burning in right eye at post-dose | 0.14 mm | Standard Deviation 0.65 |
| Placebo | Ocular Symptoms | Foreign body sensation in right eye at post-dose | 0.33 mm | Standard Deviation 1.06 |
| Placebo | Ocular Symptoms | burning in right eye at follow-up | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Itching in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Stinging in right eye at screening | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Foreign body sensation in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Stinging in right eye at pre-dose | 0 mm | Standard Deviation 0 |
| Placebo | Ocular Symptoms | Itching in right eye at post-dose | 0.14 mm | Standard Deviation 0.65 |
| Placebo | Ocular Symptoms | Stinging in right eye at post-dose | 0.05 mm | Standard Deviation 0.22 |
Secondary
Time to Anesthesia, Evaluated by Conjunctiva Pinching (0.3-mm Forceps) - Only Study Eye (Right Eye)
Time to anesthesia, evaluated by conjunctiva pinching (0.3-mm forceps) - only study eye (right eye)
Time frame: Day 1
Population: A total of 105 healthy men and women were planned and enrolled included in the study. Initially, local tolerability and safety was evaluated in the first 20 enrolled subjects . After the first 20 subjects had completed the study, local tolerability and safety data were evaluated and treatment safety was confirmed according to the clinical study protocol specifications. Efficacy, beside local tolerability and safety, was assessed in the 85 subsequent subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chloroprocaine | Time to Anesthesia, Evaluated by Conjunctiva Pinching (0.3-mm Forceps) - Only Study Eye (Right Eye) | 2.41 minutes | Standard Deviation 2.12 |
| Placebo | Time to Anesthesia, Evaluated by Conjunctiva Pinching (0.3-mm Forceps) - Only Study Eye (Right Eye) | 4.49 minutes | Standard Deviation 1.44 |
Secondary
Visual Acuity (EDTRS Chart) - Both Eyes
Visual acuity will be assessed, for all subjects and both eyes using an EDTRS chart (visual acuity is scored with reference to the logarithm of the minimum angle of resolution, an observer who can resolve details as small as 1 minute of visual angle scores LogMAR 0, since the base-10 logarithm of 1 is 0; an observer who can resolve details as small as 2 minutes of visual angle (i.e., reduced acuity) scores LogMAR 0.3, since the base-10 logarithm of 2 is near-approximately 0.3; and so on)
Time frame: Up to day 7
Population: A total of 105 healthy men and women were planned and enrolled included in the study. Initially, local tolerability and safety was evaluated in the first 20 enrolled subjects . After the first 20 subjects had completed the study, local tolerability and safety data were evaluated and treatment safety was confirmed according to the clinical study protocol specifications. Efficacy, beside local tolerability and safety, was assessed in the 85 subsequent subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Visual Acuity (EDTRS Chart) - Both Eyes | screening right eye | 1 LogMAR | Standard Deviation 0.1 |
| Chloroprocaine | Visual Acuity (EDTRS Chart) - Both Eyes | follow up right eye | 1 LogMAR | Standard Deviation 0.1 |
| Chloroprocaine | Visual Acuity (EDTRS Chart) - Both Eyes | screening left eye | 1 LogMAR | Standard Deviation 0.2 |
| Chloroprocaine | Visual Acuity (EDTRS Chart) - Both Eyes | follow up left eye | 1 LogMAR | Standard Deviation 0.1 |
| Placebo | Visual Acuity (EDTRS Chart) - Both Eyes | follow up left eye | 1 LogMAR | Standard Deviation 0.1 |
| Placebo | Visual Acuity (EDTRS Chart) - Both Eyes | screening right eye | 0.9 LogMAR | Standard Deviation 0.2 |
| Placebo | Visual Acuity (EDTRS Chart) - Both Eyes | screening left eye | 1 LogMAR | Standard Deviation 0.1 |
| Placebo | Visual Acuity (EDTRS Chart) - Both Eyes | follow up right eye | 1 LogMAR | Standard Deviation 0.1 |
Secondary
Vital Signs (Blood Pressure)
Subjects blood pressure will be measured by the Investigator or his/her deputy
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Vital Signs (Blood Pressure) | Systolic - predose | 115.6 mmHg | Standard Deviation 10.2 |
| Chloroprocaine | Vital Signs (Blood Pressure) | systolic - postdose | 116 mmHg | Standard Deviation 11.8 |
| Chloroprocaine | Vital Signs (Blood Pressure) | diastolic - predose | 71.7 mmHg | Standard Deviation 11.5 |
| Chloroprocaine | Vital Signs (Blood Pressure) | diastolic - postdose | 72.0 mmHg | Standard Deviation 11.5 |
| Placebo | Vital Signs (Blood Pressure) | diastolic - postdose | 71 mmHg | Standard Deviation 10.6 |
| Placebo | Vital Signs (Blood Pressure) | Systolic - predose | 120.4 mmHg | Standard Deviation 10.4 |
| Placebo | Vital Signs (Blood Pressure) | diastolic - predose | 73.5 mmHg | Standard Deviation 10.1 |
| Placebo | Vital Signs (Blood Pressure) | systolic - postdose | 115.3 mmHg | Standard Deviation 10.1 |
Secondary
Vital Signs (Heart Rate)
Subjects heart rate will be measured by the Investigator or his/her deputy
Time frame: Up to day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chloroprocaine | Vital Signs (Heart Rate) | pre-dose | 72.7 beats/minute | Standard Deviation 10.1 |
| Chloroprocaine | Vital Signs (Heart Rate) | post-dose | 68.4 beats/minute | Standard Deviation 8.8 |
| Placebo | Vital Signs (Heart Rate) | pre-dose | 70.7 beats/minute | Standard Deviation 10 |
| Placebo | Vital Signs (Heart Rate) | post-dose | 67.3 beats/minute | Standard Deviation 8.6 |