Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno® (PRO-122/I)

Phase I Clinical Study, to Evaluate the Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno®, Elaborated by Sophia Laboratories, S.A. of C.V. on the Ocular Surface of Ophthalmologically and Clinically Healthy Subjects

Therapeutic indication: Ocular hypotensive Use: Primary open-angle glaucoma and ocular hypertension.

Objectives: To evaluate the safety and tolerability of the preservative-free formulation PRO-122 manufactured by Sophia Laboratories, S.A. of C.V. on the ocular surface of clinically healthy subjects.

Hypothesis: The ophthalmic solution PRO-122 presents a profile of safety and tolerability similar to Krytantek Ofteno®, in healthy subjects.

Methodology: Phase I clinical trial, controlled, parallel group, double blind, randomized.

Number of patients: n=24 12 subjects per group (both eyes). Main inclusion criteria:Clinically healthy subjects.

Study Overview

• Status: Completed
• Conditions: Glaucoma
• Intervention / Treatment: Drug: PRO-122; Drug: Krytantek Ofteno®

Detailed Description

Number of patients: n = 24 12 subjects per group (both eyes). Main inclusion criteria: Clinically healthy subjects.

Treatment duration: 7 days. Duration of subject in the study: 15 to 22 days.

Adverse events will be reported and cataloged based on the MedDRA dictionary and will be reported to the corresponding regulatory entity.

The sponsor will carry out monitoring or quality visits to the research sites where it corroborates the information of the source documents and will contrast them with the information presented in the electronic CRF. Electronic case report forms will be evaluated by the clinical research associate and the clinical team of the sponsor (medical ophthalmologist researcher and pharmacologist of clinical safety).

Statistical methodology:

The data will be expressed with measures of central tendency: mean and standard deviation for the quantitative variables. The qualitative variables will be presented in frequencies and percentages. The statistical analysis will be carried out by means of the Mann-Whitney U test for the quantitative variables for the difference between the groups. The difference between the qualitative variables will be analyzed by means of X2 (Chi2). An alpha ≤ 0.05 will be considered significant.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44190
      • Unidad Clínica de Bioequivalencia, S. de R.L. de C.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• - Clinically healthy
• Ability to give your signed informed consent, and show willingness to comply with study procedures and to modify your lifestyle activities (Section 6.2.2)
• Age between 18 to 45 years.
• Indistinct sex.
• Women must ensure a hormonal contraceptive method or intrauterine device during the study period.

• Blood tests: within normal parameters or with a range of ± 20% as long as the subject is clinically healthy.

  • Blood count (BH): Hemoglobin, erythrocytes, hematocrit, total leukocytes, platelets, mean corpuscular volume and mean corpuscular hemoglobin.
  • Blood chemistry of three elements (QS): Glucose, urea and creatinine.
  • Liver function tests (PFH): Aspartate Aminotransferase and Alanine Aminotransferase, total bilirubin, direct and indirect.
• Visual ability 20/30 or better in both eyes.
• Vital signs within normal parameters.
• Intraocular pressure ≥10 and ≤ 21 mmHg.

Exclusion Criteria:

• Users of topical ophthalmic products of any kind.
• Users of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women.
• Women who are pregnant or breastfeeding.
• Participation in clinical research studies 90 days prior to inclusion in the present study.
• Previous participation in this same study.
• Users of contact lenses.
• History of any chronic-degenerative disease.
• Inflammatory or infectious disease, active at the time of study entry.
• Injuries or traumatisms not resolved at the time of admission to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRO-122; - Dosage: 1 drop every 12 hours, in both eyes	Drug: PRO-122; PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico.; Route of administration: topical ophthalmic.; Other Names: timolol 0.5%; brimonidine 0.2%; dorzolamide 2%; Krytantek PF; Krytantek Ofteno® Preservative Free
Active Comparator: Krytantek Ofteno®; - Dosage: 1 drop every 12 hours, in both eyes	Drug: Krytantek Ofteno®; - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico.; - Route of administration: topical ophthalmic.; Other Names: timolol 0.5%; brimonidine 0.2%; dorzolamide 2%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	primary security variable the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. it will be evaluated by the number of reported cases per group.	during the 14 days of evaluation, including the safety call (day 14)
Eye Comfort Index	It is a questionnaire designed to measure the irritation of the ocular surface with Rasch analysis to produce estimates on a linear scale of intervals (ratings: 0-100).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort.	will be evaluated at the end of the treatment, at the final visit (day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Eyes With Epithelial Defects by Grade	The epithelial defects will be evaluated by means of two stains, green lissamine and fluorescein, it is a discrete variable that will be realized by direct observation, it will be staged according to the degrees of the oxford scale that go from 0 to 5 (0-V) according to its severity, where 0 is the normal lower limit and 5 the upper limit of defects.	will be evaluated at the end of the treatment, at the final visit (day 8)
Visual Ability	The visual capacity variable will be reported using as a unit of measure a fraction, this is taken from a visual test with the Snellen primer, it is a Nominal type variable. where the optimal vision is 20/20 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc.	will be evaluated at the end of the treatment, at the final visit (day 8)
Participants With Conjunctival Hyperemia (CH) by Grade	Conjunctival hyperemia will be evaluated as an ordinal variable, by direct observation and staged using the Efron scale as Normal / Very Light / Mild / Moderate / Severe. Based on this scale, the normal and mild stages are considered without pathologies or normal. Mild, moderate and severe are considered pathological.	will be evaluated at the end of the treatment, at the final visit (day 8)
Participants With Chemosis	The chemosis will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent.	will be evaluated at the end of the treatment, at the final visit (day 8)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Intraocular Pressure	the intraocular pressure will be evaluated by means of the Goldman applanation tonometry whose unit of measurement is millimeters of mercury (mmHg), it is a continuous variable and its normality range is between 11 - 21 mmHg	will be evaluated at the end of the treatment, at the final visit (day 8)

Collaborators and Investigators

• Sponsor: Laboratorios Sophia S.A de C.V.

Publications and helpful links

General Publications

• Munoz-Villegas P, Navarro-Sanchez AA, Sanchez-Rios A, Olvera-Montano O, Baiza-Duran LM. Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials. Ther Clin Risk Manag. 2021 Oct 21;17:1123-1134. doi: 10.2147/TCRM.S331294. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): August 30, 2019

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: May 28, 2019
• First Posted (Actual): May 29, 2019

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Glaucoma; Krytantek; Krytantek PF; PRO-122
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Carbonic Anhydrase Inhibitors; Timolol; Brimonidine Tartrate; Dorzolamide
• Other Study ID Numbers: SOPH122-0518/I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No