Dorzolamide+Timolol Multidose Preservative-free vs Dorzolamida+Timolol BAK Preserved Efficacy and Safety

Phase IV, Multicenter, Double-blind, Randomized, Controlled, Parallel-group, Trial to Evaluate the Efficacy and Safety of Dozolamide 2%/Timolol 0,5% PF vs Dorzolamide 2%/Timolol 0,5% BAK-preserved in OAG or OH

The goal of this study is to evaluate the tolerability of the new formulation of Dorzolamide+Timolol preservative free developed in OSD Aptar Pharma multidose system in comparison with Dorzolamide +Timolol BAK preserved ophthalmic formulation.

Study Overview

• Status: Recruiting
• Conditions: Ocular Hypertension; Glaucoma, Open-Angle
• Intervention / Treatment: Drug: Dorzolamide / Timolol Ophthalmic Solution; Drug: dorzolamide/timolol

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Melina del Papa; Phone Number: 01160480067; Email: mdelpapa@poen.net.ar
• Study Contact Backup: Name: Silvia Passerini, PharmD

Study Locations

• Argentina
  • Ciudad autónoma de Buenos Aires, Argentina, C1425FAB
    • Active, not recruiting
    • Consultorios de Oftalmología
  • Buenos Aires
    • Olivos, Buenos Aires, Argentina, B1636CSS
      • Recruiting
      • Clínica de Ojos Dr. Nano
      • Contact: Fernando Cataldi, MD; Phone Number: +54 9 11 5830-2200
      • Principal Investigator: Fernando Cataldi, MD
      • Sub-Investigator: Melanie Whity, MD
  • Ciudad Autónoma De Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina, C1007ABK
      • Active, not recruiting
      • Consultorio Dr. Peyret
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina, C1122AAK
      • Recruiting
      • Gonella Oftalmólogos
      • Contact: Ana Sanseau, MD; Phone Number: +54 9 11 5002-4211
      • Principal Investigator: Ana Sanseau, MD
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina, C1425AYA
      • Active, not recruiting
      • Centro Diagnóstico Dr. Gentile
    • Ciudad Autónoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina, C1124
      • Not yet recruiting
      • Centro oftalmológico Dr. Casiraghi & asociados
      • Contact: Javier Casiraghi, MD; Phone Number: 011 4822-0364
      • Principal Investigator: Javier Casiraghi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Older than 18 years old
• Patients with POAG and OH
• PIO < 20 mmHg
• Under treatment with Dorzolamide + Timolol BAK preserved at least 6 month after
• OSDI > 13 & one of these ocular signs (BUT <6sec or Schirmer test < 5 mm/5min or corneal staining positive)
• Corneal thickness between 520-580 um.

Exclusion Criteria:

• Patient with severe respiratory diseases (asthma, COPD and other bronchospactic diseases).
• Patient with cardiovascular diseases (Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock).
• Severe renal impairment (CrCl <30 mL/min)
• Progressive diseases of the retina other than glaucoma
• Inflammation and/or infecctions active
• Ocular surface syndrome other than Ocular Surface disease
• Eyelid disorder
• Systemic adminsitration of Betablockers or carbonic anhydrase inhibitors
• Patient that requires another antigluacomatous eye drop other than fixed combination of Dorzolamide/Timolol
• Patients who use regularly lubricant eye drops
• Patient who use regularly contact lenses
• Patient with autoinmune diseases
• Patients who underwent kerato-refractive laser procedures, cornea or corneal surface surgery, including, but not limited to, LASIK and PRK, within 6 months prior to the baseline visit.
• Patients who have undergone a laser procedure or intraocular surgery or extraocular in either eye within 6 months prior to the baseline visit.
• Patients with severe central visual field loss in either eye based onclinical judgment of the investigator. For the Humphrey and Octopus perimeters, the severe loss The visual field is defined as a sensitivity less than or equal to 10 dB in at least two(2) of the four (4) visual field test points closest to the fixation point
• Patients with known hypersensitivity to any of the components of bothdrugs under study.
• Pregnant or lactating women.
• Women of childbearing age who are not using a contraceptive method.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dorzolamide+Timolol PF; Glaucotensil TD LC, Laboratorios Poen	Drug: Dorzolamide / Timolol Ophthalmic Solution; Dorzolamide-timolol fixed combination in a preservative-free multidose device; Other Names: Glaucotensil TD LC
Experimental: Dorzolamide + Timolol BAK; Glaucotensil TD, Laboratorios Poen	Drug: dorzolamide/timolol; Dorzolamide-timolol BAK-preserved fixed combination; Other Names: Glaucotensil TD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Surface Disease Symptoms	OSDI questtionarie	Change from baseline in OSDI score at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular preassure	Intraocular preassure (PIO) by GAT	Change from baseline in PIO (mmHg) at 24 weeks
Break-up Time	Break-up Time (BUT)	Change from baseline BUT (seconds) at 24 weeks
SCHIRMER-ITEST	Schirmer test without anesthesia	Change from baseline Shirmer test (mm) at 24 weeks
Conjunctival Hyperemia	Conjunctival Hyperemia	Change from baseline in porcentaje of patients with conjunctival hyperemia at 24 weeks
Satisfaction questionnaire	Satisfaction questionnaire	Change from baseline of patient satisfaction at 24 weeks using a 5-point likert scale
Best corrected visual acuity	snellen scale 20/20	Change from baseline visual acuity at 24 weeks
Treatment preference	Treatment preference	Treatment preference with respect previous treatment at Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Superficial corneal epithelium density	Superficial corneal epithelium density analyzed by confocal microscopy expresed by cells /mm2	Change from baseline superficial corneal epithelium density at 48 weeks
Basal corneal epithelium density	Basal corneal epithelium density analyzed by confocal microscopy expresed by cells /mm2	Change from baseline basal corneal epithelium density at 48 weeks
Corneal Estroma reflectivity	Corneal Estroma reflectivity analyzed by confocal microscopy expresed by 5-point scale of grade	Change from baseline in the grade of corneal estroma reflectivity at 48 weeks specify by 4 grade scale reported by Martone et al. .
Corneal nerve density	Corneal nerve density analyzed by confocal microscopy expresed by cells /mm2	Change from baseline corneal nerve density at 48 weeks
Neuroma density	Neuroma density analyzed by confocal microscopy expresed by neuromas/mm2	Change from baseline neuroma density at 48 weeks
Dendrite density	Dendrite density analyzed by confocal microscopy expresed by dendrites/mm2	Change from baseline dendrite density at 48 weeks
Corneal nerve tortuosity	Corneal nerve tortuosity analyzed by confocal microscopy expresed by 5-point scale of grade	Change from baseline in the grade of corneal nerve tortousity at 48 weeksusing a 5 point scale reported by Oliviera-Soto et al.
Endothelial cell density	endothelial cell density analyzed by confocal microscopy expresed by cells/mm2	Change from baseline endothelial cell count at 48 weeks
Conjuctival epithelium density	Conjuntival epithelium density analyzed by confocal microscopy expresed by cells/mm2	Change from baseline conjuctival epithelium density at 48 weeks
Goblett cell density	Goblett cell density nalyzed by confocal microscopy expresed by cells/mm2	Change from baseline goblett cell density at 48 weeks
Inflamatory infiltrates	Description of presence or absence of inflamtory cells on conjuntiva	Change from baseline in inflamatory infiltrates at 48 weeks

Collaborators and Investigators

• Sponsor: Laboratorios Poen

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2023
• Primary Completion (Estimated): October 4, 2024
• Study Completion (Estimated): November 15, 2024

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; 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; Carbonic Anhydrase Inhibitors; Pharmaceutical Solutions; Timolol; Dorzolamide; Ophthalmic Solutions
• Other Study ID Numbers: ANTIGLAULC01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No