Glaucoma, Open-Angle, Ocular Hypertension
Conditions
Brief summary
Phase IV randomized, double blind, multicenter, parallel group clinical study to evaluate the efficacy of the combined use of Krytantek Ofteno PF® and Gaap Ofteno PF®, both applied every 12 hours, versus the use of Eliptic Ofteno PF® Plus Gaap Ofteno PF®, both applied every 12 hours, in patients with open angle glaucoma or ocular hypertension during 90 days
Interventions
DRUGDorzolamide-timolol-brimonidine and latanoprost
Application of Gaap Ofteno PF® every 24 hrs for 30 days plus concomitant application of Krytantek Ofteno PF® every 12 hours for 60 days. Total intervention time: 90 days.
DRUGDorzolamide-timolol and latanoprost
Application of Gaap Ofteno PF® every 24 hrs for 30 days plus concomitant application of Eliptic Ofteno PF® every 12 hours for 60 days. Total intervention time: 90 days.
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
After signing the informed consent form (ICF), every subject will receive a coded patient number. Randomization will take place through and integrated web response system (IWRS). In the first step, during the eligibility visit, all patients will be assigned the same treatment (Gaap Ofteno PF®). After one month, patients that once again comply with the inclusion criteria will be assigned randomly (1:1) to one of the two investigation products, either Krytantek Ofteno PF® or Eliptic Ofteno PF®.
Intervention model description
Randomized, double blind, multicenter with parallel groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with primary open-angle glaucoma (according to the Preferred Practice Pattern guidelines of the American Academy of Ophthalmology) or ocular hypertension, not controlled by a prostaglandin analogue or a β-blocker in the eye to be included in the study. * Previous treatment for at least 30 days prior to the eligibility visit with a prostaglandin analogue or a β-blocker in the eye to be included in the study. * Intraocular pressure measured by Goldmann tonometry ≥ 19 and ≤ 26 mmHg in the eye to be included in the study. * Ability to voluntarily provide informed consent. * Ability and willingness to comply with scheduled visits, treatment plan, and other study procedures. * Age ≥ 18 years.
Exclusion criteria
* Pregnant, breastfeeding, or planning to become pregnant during the clinical study. * For women of reproductive age, not using a hormonal contraceptive method, intrauterine device, or bilateral tubal ligation. * Anterior chamber angle \< 2 in the Shaffer Classification or presence of peripheral anterior synechiae in the eye to be included in the study. * Currently undergoing treatment with any systemic ocular hypotensive agent (e.g., mannitol, glycerin, isosorbide). * Best Corrected Visual Acuity worse than 20/200 in the eye to be included in the study. * Severe central visual field loss (sensitivity ≤ 10 dB in ≥ 2 of the 4 central points of the visual field fixation point) in the eye to be included in the study. * History of ocular surgery or laser eye procedure in the last 6 months in the eye to be included in the study. * History of ocular trauma in the last 6 months in the eye to be included in the study. * History of chronic uveitis in the eye to be included in the study. * History of intraocular, periocular, retrobulbar, subconjunctival, or subtenon injection in the last 6 months in the eye to be included in the study. * Patients with silicone, or who have had silicone in the anterior or posterior segment of the eye to be included in the study. * Diagnosis of aphakia in the eye to be included in the study. * Any corneal abnormality that decreases the reliability of Goldmann tonometry in the eye to be included in the study. * Known hypersensitivity to the active ingredients used in the study (prostaglandin analogues, β-adrenergic blockers, α2-adrenergic agonists, carbonic anhydrase inhibitors). * Diseases that contraindicate the use of the active ingredients used in the study (e.g., severe asthma or COPD, 2nd or 3rd degree atrioventricular block not controlled by a pacemaker, sinus bradycardia, manifest heart failure, Chronic Kidney - - Disease with a CrCl \< 30 ml/min). * Patients requiring the use of monoamine oxidase inhibitors (MAOIs), and patients treated with antidepressants affecting noradrenergic transmission (e.g., tricyclic antidepressants and mianserin). * Patients who use, or have used in the last month, topical ocular steroids in the eye to be included in the study, or steroids via oral, intravenous, intramuscular, dermal, or intralesional routes. * Have participated in another clinical research study within 30 days prior to signing the informed consent form (ICF). * Have previously participated in this study. * Have a history of drug addiction within the last two years prior to signing the ICF. * Have any type of surgical intervention planned during the study period. * Be or have an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is part of the research site personnel or the sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intraocular Pressure (IOP) | Days: -30 (± 2) (eligibility visit), 0 (basal visit), 14 (± 2) (first follow-up visit), 30 (± 2) (second follow-up visit) and 60 (± 2) (final visit) | Measured through Goldman tonometer in milligrams of mercury (mmHg). After instillation of topical anesthetic (tetracaine 0.5%) and fluorescein stain, IOP is evaluated at 9:00 and at 11:00 hrs. (± 30 minutes). Both measurements and their average will be registered. Normal values are considered between 10 and 21 mmHg. Assessed at the eligibility visit, basal visit, first follow-up visit, second follow-up visit, and final visit, reported only for first follow-up visit, second follow-up visit and final visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Ocular Comfort Index | Days: -30 (± 2) (eligibility visit), 0 (basal visit), 14 (± 2) (first follow-up visit), 30 (± 2) (second follow-up visit) and 60 (± 2) (final visit) | Ocular Comfort Index (OCI) Questionnaire will be used for evaluation of tolerability through incidence and severity of dry eye symptoms in a scale from 0 to 100. Greater scores mean a worse outcome. |
| Change in Ocular Surface Integrity (Conjunctival Hyperemia) | Days: 0 (basal visit, BV), 14 (± 2) (first follow-up visit, V1), 30 (± 2) (second follow-up visit, V2) and 60 (± 2) (final visit, FV) | By means of a slit lamp conjunctival hyperemia will be evaluated. Conjunctival hyperemia will be graded according to Efron's scale (5 grades: Normal (0), Very Mild (I), Mild (II), Moderate (3), and Severe (4)). |
| Best Corrected Visual Acuity (BCVA) | Days: -30 (± 2) (eligibility visit), 0 (basal visit [BV]), 14 (± 2) (first follow-up visit [V1]), 30 (± 2) (second follow-up visit [V2]) and 60 (± 2) (final visit [FV]) | 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. BCVA was compared between groups and between visits. Assessed at the eligibility visit, basal visit, first follow-up visit, second follow-up visit, and final visit, reported only for first follow-up visit, second follow-up visit and final visit. |
| Optic Nerve Cup/Disc Ratio (Baseline Vist vs Final Visit) | Days: 0 (basal visit) and 60 (± 2) (final visit) | Both clinical and imaging evaluation will be performed. For clinical evaluation, after the application of a topical ophthalmic mydriatic (tropicamide 0.8% / phenylephrine 5%), indirect ophthalmoscopy will be performed through the aid of a fundus lens in a slit lamp. For imaging, optic coherence tomography (OCT) will be used. Assessed and reported only for the basal visit and final visit. |
| Mean Value in Nerve Fibers and Ganglion Cell Thickness | Days: 0 (basal visit) and 60 (± 2) (final visit) | Spectral domain OCT is a non invasive tool that will be used to evaluate quantitatively the thickness of retinal nerve fibers and ganglion cell layers. The mean observed in the nerve fibers and ganglion cell thickness was calculated. This was assessed and reported only for the basal and final visit. |
| Optic Nerve Image | Days: -30 (± 2) (eligibility visit), 0 (basal visit) and 60 (± 2) (final visit) | Through a fundus camera a photograph will be taken to obtain a faithful record of any possible changes to the optic nerve head characteristics. Its classification as "small", "medium" or "large" relied on the expertise of the PI, the percentage of cases in each classification ("small", "medium" or "large") was reported. Assessed and reported only for the basal visit and final visit. |
| Central Corneal Thickness (CCT) | Days: 0 (basal visit) and 60 (± 2) (final visit) | Measured through ultrasonic pachymetry, three assessments will be performed, these and its average will be recorded. Assessed and reported for the basal visit and final visit. |
| Change in Visual Fields | Days: 0 (basal visit) and 60 (± 2) (final visit) | Visual fields will be assessed using standard automated SITA (Swedish Interactive Thresholding Algorithm) white-on-white perimetry performed with a Humphrey perimeter. To be considered reliable, fixation losses, false positives, and false negatives must be less than 20%. The mean deviation (MD) was recorded, which is a measure of overall field loss. The standard deviation of the pattern was also recorded, which is a measure of focal loss or variability within the field. A higher score is a worse result. The theoretical value or reported range for the average deviation is from +2.00 to -35 dB. |
| Number of Adverse Events | Day: 75 (± 3) (safety call) | Presence/absence adverse events, defined as the appearance of any unfavorable reaction in a patient participating in a clinical investigation in which any pharmaceutical product is being administered, regardless of the causal attribution. |
| Change in Ocular Surface Integrity (Chemosis) | Days: 0 (basal visit, BV), 14 (± 2) (first follow-up visit, V1), 30 (± 2) (second follow-up visit, V2) and 60 (± 2) (final visit, FV) | By means of a slit lamp chemosis will be evaluated. Chemosis will be evaluated as present (if conjunctiva separates from the sclera in ≥ 1/3 of the palpebral opening area or if it exceeds the eyelid's gray line) or absent. The number and percentage of participants in each category was reported. |
Countries
Mexico
Participant flow
Pre-assignment details
Participant randomization was conducted in a 1:1 ratio. When a participant enrolled both eyes in the study, both received the same treatment assignment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 67.3 years STANDARD_DEVIATION 10.73 |
| Best Corrected Visual Acuity (BCVA) | 0.71 decimals STANDARD_DEVIATION 0.21 |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment Mexico | 14 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 | 0 / 12 | 0 / 14 |
| other Total, other adverse events | 14 / 23 | 18 / 24 | 8 / 12 | 4 / 14 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 12 | 0 / 14 |
Outcome results
None listed