Dry Eye
Conditions
Keywords
Dry eye, propylene glycol
Brief summary
Study design: Phase I-II clinical trial, comparative, non-inferiority with active control, parallel groups, double blind with randomisation. Safety analysis when completing the visits of the first 12 subjects of the Nanodrop® group, if there are less than 20% of unexpected Events (EA), related to the research product, recruitment is continued until the sample is completed for efficacy analysis objectives Security: Evaluate the safety of the ophthalmic application of Nanodrop® by quantifying the incidence of unexpected Adverse Events (EA) related to the research product (PI). Effectiveness: Demonstrate the non-inferiority of Nanodrop® compared to Systane® Balance, in the efficacy of the treatment of patients with dry eye, by means of the Ocular Surface Disease Index (OSDI). Hypothesis Security: H0 = Nanodrop® is safe in its ophthalmic application as it presents an incidence of unexpected adverse events related to the research drug, less than 20% of the population of Nanodrop® safety group. H1 = Nanodrop® is not safe in its ophthalmic application, as it presents an incidence of unexpected adverse events related to the research drug, exceeding 20% of the population of Nanodrop® safety group. Effectiveness: H0 = Nanodrop® is lower than Systane® Balance by more than 5 points in the OSDI test score. H1 = Nanodrop® is lower than Systane® Balance by 5 points or less in the OSDI test score. Number of subjects: n = 126 evaluable subjects 63 evaluable subjects per group (both eyes). Main inclusion criteria: Dry eye diagnosis Duration of intervention treatment: 28 days Approximate duration of the subject in the study: 35 days
Interventions
DRUGNanodrop®
minimum to meet 1 drop 4 times a day, both eyes
DRUGSystane Balance
minimum to meet 1 drop 4 times a day, both eyes
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking will be done through the primary and secondary packaging. They will be identified by means of identical tags. Which, in compliance with current and applicable regulations, must contain at least: * Name, address and telephone number of the sponsor. * Pharmaceutical form and route of administration. * Lot Number. * Legend Exclusively for clinical studies * Date of Expiry.
Intervention model description
Phase I-II clinical trial, comparative, non-inferiority with active control, double blind with randomisation. Safety analysis when completing the visits of the first 12 subjects
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have the ability to voluntarily grant your signed informed consent * Power and willingness to comply with scheduled visits treatment plan and other study procedures * Be willing to modify the activities of your lifestyle. * Be of legal age * Women of reproductive age should ensure continuation (initiated ≥ 30 days prior to the signing of the Informed Consent Form or ICF) of using a hormonal contraceptive method or intrauterine device (IUD) during the study period * Present a dry eye diagnosis, defined by: OSDI ≥ 13 points plus one of the following: * Corneal staining with more than 5 sites * Conjunctival staining with more than 9 sites * Breakup Time of lacrimal film (BUT) \<10 seconds:
Exclusion criteria
* In the case of women: being pregnant, breastfeeding or planning to get pregnant within the study period. * Have participated in another clinical research study ≤ 30 days before the scrutiny visit. * Having previously participated in this study. * Present a Better Corrected Visual Acuity (MAVC) of 20/200 or worse in one of the eyes. * Present an added ophthalmological diagnosis of: Allergic, viral or bacterial conjunctivitis. Anterior blepharitis. Demodex. Eye parasitic infections. Unresolved eye trauma. Healing diseases of the ocular surface. Corneal or conjunctival ulcers. Filamentous keratitis. Neurotrophic keratitis. Bullous keratopathy. Neoplastic diseases on the ocular surface or annexes. Diseases with fibrovascular proliferations on the conjunctival and / or corneal surface. Diseases in the retina and / or posterior segment that require treatment or threaten the visual prognosis. Glaucoma * Have a management of your dry eye that requires the implementation of stage 2 treatments of the recommendations in the treatment and management by stages for the dry eye disease from the Dry Eye Workshop II of The Tear Film and Ocular Surface Society (DEWS II, TFOS). * Have a history of drug addiction or current drug dependence or within the last two years prior to the signing of the Informed Consent Form. * Have a history of ocular surgical procedure within the last 3 months prior to the signing of the Informed Consent Form. * Be a user of soft or hard contact lenses. You can enter if you can suspend your use during the study, you must turn 15 days without using the contact lens before inclusion. * Having another medical condition, acute or chronic, that at the discretion of the researcher could increase the risk associated with participation in the study or administration of the product under investigation, or that could interfere with the interpretation of the results of the study. * Present known hypersensitivity to the components of the products under investigation. * Be or have an immediate family member (for example: spouse, parent / legal guardian, brother or child) who is an employee of the research site or the sponsor, and who participates directly in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Surface Disease Index (OSDI) | will be evaluated at the end of the treatment (day 29, final visit) | OSDI is a questionnaire designed to measure eye surface irritation with Rasch analysis to produce estimates on a linear interval scale.. The OSDI score ranges from 0 to 100, with higher scores indicating greater severity of symptoms. A score of 0 represents no symptoms, while 100 represents the most severe symptoms. |
| Percentage of Unexpected Adverse Events (AE) Related to the Research Product | during the 29 days of evaluation, including the safety call | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epithelial Defects (ED) Green Lissamine | will be evaluated at the end of the treatment (day 29, final visit) | The epithelial defects will be evaluated by green lissamine, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA). In the CTO, grade 0 is defined as the presence of 0 to 9 lissamine green staining points in the interpalpebral bulbar conjunctiva (qualifying the temporal and nasal portion separately); grade 1 is defined by the presence of 10 to 32 points; grade 2 by 33 to 100; and grade 3 for\> 100 points. Due to the difficulty of counting individual points in a moving eye, any area ≥ 4mm2 of confluent points is considered\> 100 points. A higher score is a worse outcome. |
| Visual Acuity (VA) | will be evaluated at the end of the treatment (day 29, final visit) | Visual acuity (VA) is a test of visual function. It will be evaluated with the Snellen chart. The Snellen chart is the standard tool used to evaluate visual acuity. It was located in a place with adequate lighting, natural or artificial and at a distance of 3 meters from the subject to be evaluated. The contralateral eye to which it will be evaluated is covered, then the examiner detects until the line can clearly see the letters given he or she a score, the normal score for a VA is 20/20.This score can be expressed in fraction (i.e. 20/20) decimal (i.e. 1.0), or LogMAR (i.e. 0) formats. In this study, VA is expressed in decimal format. In decimal format, a lower number is a worse outcome. |
| Tear Breakup Time (TBUT) | will be evaluated at the end of the treatment (day 29, final visit) | brake up time of the tear film One of the first aspects of the tear film that changes when there is an alteration to the ocular surface is its stability. In general, if the corneal or conjunctival surface is damaged, it is unlikely that a stable tear film can be maintained. The most common method to evaluate tear film stability is the evaluation of TBUT with fluorescein. Once the fluorescein is instilled, with the cobalt blue filter the patient is asked not to blink after having blinked 1 to 2 times. The colored precorneal fluorescein layer will change to less fluorescent or non-fluorescent regions. The time that elapses from the last blink to the appearance of these regions is the TBUT. It will be reported in seconds. |
| Incidence of Expected Adverse Events | will be evaluated at the end of the treatment (day 29, final visit) | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent |
| Epithelial Defects (ED) Fluorescein Stain | will be evaluated at the end of the treatment (day 29, final visit) | The epithelial defects will be evaluated by fluorescein, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA).According to the CTO, grade 0 corresponds to the absence of dotted epithelial erosions (EEP); Grade 1 is defined as the presence of 1-5 EEP; Grade 2 corresponds to 6-30 EEP; and\> 30 EEP will be classified as grade 3. Additionally a qualification point will be added if: 1) EEP is presented in the central portion of the cornea with a diameter of 4mm; 2) filaments are observed and 3) confluent staining patches are observed, including linear stains. A greater score is a worse outcome. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nanodrop® (PRO-176) \- Nanodrop®. 0.6% propylene glycol. Ophthalmic emulsion Laboratorios Sophia, S.A. from C.V. Route of administration: Ophthalmic.
Nanodrop®: minimum to meet 1 drop 4 times a day, both eyes | 63 |
| Nanodrop® (PRO-176) \- Nanodrop®. 0.6% propylene glycol. Ophthalmic emulsion Laboratorios Sophia, S.A. from C.V. Route of administration: Ophthalmic.
Nanodrop®: minimum to meet 1 drop 4 times a day, both eyes | 126 |
| Systane® Balance * Systane® Balance. 0.6% propylene glycol. Ophthalmic emulsion Alcon Laboratories, Inc.
* Route of administration: Ophthalmic.
Systane Balance: minimum to meet 1 drop 4 times a day, both eyes | 63 |
| Systane® Balance * Systane® Balance. 0.6% propylene glycol. Ophthalmic emulsion Alcon Laboratories, Inc.
* Route of administration: Ophthalmic.
Systane Balance: minimum to meet 1 drop 4 times a day, both eyes | 126 |
| Total | 378 |
Baseline characteristics
| Characteristic | Nanodrop® (PRO-176) | Systane® Balance | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 6 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 57 Participants | 110 Participants |
| Age, Continuous | 47.8 years STANDARD_DEVIATION 17.4 | 44.6 years STANDARD_DEVIATION 15.4 | 46.18 years STANDARD_DEVIATION 16.45 |
| Intraocular Pressure (IOP) | 13.8 mmhg STANDARD_DEVIATION 3.1 | 12.7 mmhg STANDARD_DEVIATION 2.5 | 13.20 mmhg STANDARD_DEVIATION 3.41 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Mexico | 63 participants | 63 participants | 126 participants |
| Sex: Female, Male Female | 47 Participants | 40 Participants | 87 Participants |
| Sex: Female, Male Male | 16 Participants | 23 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 63 |
| other Total, other adverse events | 54 / 63 | 47 / 63 |
| serious Total, serious adverse events | 0 / 63 | 1 / 63 |
Outcome results
Primary
Ocular Surface Disease Index (OSDI)
OSDI is a questionnaire designed to measure eye surface irritation with Rasch analysis to produce estimates on a linear interval scale.. The OSDI score ranges from 0 to 100, with higher scores indicating greater severity of symptoms. A score of 0 represents no symptoms, while 100 represents the most severe symptoms.
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: The evaluated population for this outcome measure was the PP population (subjects who finished the study without presenting any mayor deviations to protocol)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nanodrop® (PRO-176) | Ocular Surface Disease Index (OSDI) | 48.9 score on a scale | Standard Deviation 19.2 |
| Systane® Balance | Ocular Surface Disease Index (OSDI) | 50.3 score on a scale | Standard Deviation 18.3 |
Primary
Percentage of Unexpected Adverse Events (AE) Related to the Research Product
the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent
Time frame: during the 29 days of evaluation, including the safety call
Population: This outcome measure considered the Intention-To-Treat (ITT) population, all participants who were randomized and exposed to treatment, regardless of whether they adhered to the study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nanodrop® (PRO-176) | Percentage of Unexpected Adverse Events (AE) Related to the Research Product | 23.0 percentage of unexpected related AE |
| Systane® Balance | Percentage of Unexpected Adverse Events (AE) Related to the Research Product | 17.5 percentage of unexpected related AE |
Secondary
Epithelial Defects (ED) Fluorescein Stain
The epithelial defects will be evaluated by fluorescein, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA).According to the CTO, grade 0 corresponds to the absence of dotted epithelial erosions (EEP); Grade 1 is defined as the presence of 1-5 EEP; Grade 2 corresponds to 6-30 EEP; and\> 30 EEP will be classified as grade 3. Additionally a qualification point will be added if: 1) EEP is presented in the central portion of the cornea with a diameter of 4mm; 2) filaments are observed and 3) confluent staining patches are observed, including linear stains. A greater score is a worse outcome.
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: The evaluated population for this outcome measure was the PP population (subjects who finished the study without presenting any mayor deviations to protocol)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nanodrop® (PRO-176) | Epithelial Defects (ED) Fluorescein Stain | 0.91 score on a scale | Standard Deviation 0.92 |
| Systane® Balance | Epithelial Defects (ED) Fluorescein Stain | 0.93 score on a scale | Standard Deviation 1.14 |
Secondary
Epithelial Defects (ED) Green Lissamine
The epithelial defects will be evaluated by green lissamine, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA). In the CTO, grade 0 is defined as the presence of 0 to 9 lissamine green staining points in the interpalpebral bulbar conjunctiva (qualifying the temporal and nasal portion separately); grade 1 is defined by the presence of 10 to 32 points; grade 2 by 33 to 100; and grade 3 for\> 100 points. Due to the difficulty of counting individual points in a moving eye, any area ≥ 4mm2 of confluent points is considered\> 100 points. A higher score is a worse outcome.
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: The evaluated population for this outcome measure was the PP population (subjects who finished the study without presenting any mayor deviations to protocol)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nanodrop® (PRO-176) | Epithelial Defects (ED) Green Lissamine | 0.83 score on a scale | Standard Deviation 0.69 |
| Systane® Balance | Epithelial Defects (ED) Green Lissamine | 0.85 score on a scale | Standard Deviation 0.78 |
Secondary
Incidence of Expected Adverse Events
the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: This outcome measure considered the Intention-To-Treat (ITT) population, all participants who were randomized and exposed to treatment, regardless of whether they adhered to the study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nanodrop® (PRO-176) | Incidence of Expected Adverse Events | 77 percentage of adverse events per group |
| Systane® Balance | Incidence of Expected Adverse Events | 82.5 percentage of adverse events per group |
Secondary
Tear Breakup Time (TBUT)
brake up time of the tear film One of the first aspects of the tear film that changes when there is an alteration to the ocular surface is its stability. In general, if the corneal or conjunctival surface is damaged, it is unlikely that a stable tear film can be maintained. The most common method to evaluate tear film stability is the evaluation of TBUT with fluorescein. Once the fluorescein is instilled, with the cobalt blue filter the patient is asked not to blink after having blinked 1 to 2 times. The colored precorneal fluorescein layer will change to less fluorescent or non-fluorescent regions. The time that elapses from the last blink to the appearance of these regions is the TBUT. It will be reported in seconds.
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: The evaluated population for this outcome measure was the PP population (subjects who finished the study without presenting any mayor deviations to protocol)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nanodrop® (PRO-176) | Tear Breakup Time (TBUT) | 2.28 reported in seconds | Standard Deviation 2.9 |
| Systane® Balance | Tear Breakup Time (TBUT) | 2.02 reported in seconds | Standard Deviation 2.9 |
Secondary
Visual Acuity (VA)
Visual acuity (VA) is a test of visual function. It will be evaluated with the Snellen chart. The Snellen chart is the standard tool used to evaluate visual acuity. It was located in a place with adequate lighting, natural or artificial and at a distance of 3 meters from the subject to be evaluated. The contralateral eye to which it will be evaluated is covered, then the examiner detects until the line can clearly see the letters given he or she a score, the normal score for a VA is 20/20.This score can be expressed in fraction (i.e. 20/20) decimal (i.e. 1.0), or LogMAR (i.e. 0) formats. In this study, VA is expressed in decimal format. In decimal format, a lower number is a worse outcome.
Time frame: will be evaluated at the end of the treatment (day 29, final visit)
Population: The evaluated population for this outcome measure was the PP population (subjects who finished the study without presenting any mayor deviations to protocol)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nanodrop® (PRO-176) | Visual Acuity (VA) | 0.89 decimal score (Snellen Chart) | Standard Deviation 0.18 |
| Systane® Balance | Visual Acuity (VA) | 0.90 decimal score (Snellen Chart) | Standard Deviation 0.19 |