Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK) (CONFORTK)

• ClinicalTrials.gov Identifier: NCT03257813
• Recruitment Status: Completed
• First Posted: August 22, 2017
• Results First Posted: December 9, 2019
• Last Update Posted: December 9, 2019
• Sponsor: Laboratorios Sophia S.A de C.V.
• Information provided by (Responsible Party): Laboratorios Sophia S.A de C.V.

Study Description

Brief Summary:

Aim: To demonstrate the non-inferiority of the PRO-122 ophthalmic solution manufactured by Laboratorios Sophia S.A. de C.V. versus Krytantek Ofteno® ophthalmic solution like hypotensive therapy in subjects with primary open angle glaucoma or ocular hypertension.

Study design: a multicentric, prospective, crossover (2x2), double blind clinical study. Sample size: one hundred patients with primary open angle glaucoma or ocular hypertension. Patients in the period 1: In the first sequence 30 patients will be assigned to receive the ophthalmic solution: Krytantek Ofteno ® (timolol 0.5%%/brimonidine 0.2%/dorzolamide 2%) 1 drop B.I.D. during 30 days and the second sequence 30 patients will be assigned to receive the ophthalmic solution: PRO-122 1 drop B.I.D. during 30 days in the same period. Washout period: 20 hours. Patients in the period 2: the pharmacological intervention change to the opposite therapy for 30 days

Condition or disease	Intervention/treatment	Phase
Primary Open Angle Glaucoma; Ocular Hypertension	Drug: PRO-122; Drug: Krytantek Ofteno®	Phase 3

Detailed Description:

The American Academy of Ophthalmology Glaucoma Panel: The primary open angle glaucoma (POAG) is a progressive, chronic optic neuropathy in adults in which intraocular pressure (IOP) and other currently unknown factors contribute to damage and in which, in the absence of other identifiable causes, there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an anterior chamber angle that is open by gonioscopic appearance.

This is a multicentric, crossover, double blind and prospective clinical study. The investigators will include patients with confirmed diagnosis of primary open-angle glaucoma or ocular hypertension, with target intraocular pressure (TIOP) within a range at which a patient is likely to remain stable or at which worsening of glaucoma will be slow enough that the risk of additional intervention is not justified.

Patients will be randomly divided into 2 groups, one of them treated with a known formulation of timolol 0.5%/brimonidine 0.2%/dorzolamide 2% (Krytantek Ofteno®, Laboratorios Sophia, Mexico) and the other one treated with PRO-122 ophthalmic solution. Patients will receive 1 drop B.I.D. into the lower conjunctival sac of either formulations and were examined at days: 1, 15, 30, 45 and 61 after initiation of treatment. A phone call security at day 75 will be performed.

Primary efficacy outcome: To evaluate the efficacy of PRO-122 versus Krytantek Ofteno® instilled onto the ocular surface in subjects with primary open angle glaucoma (POAG) or ocular hypertension (HTO), to control and maintenance of the target intraocular pressure (TIOP).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment

Intervention Model Description

60 subjects with diagnosis of open angle primary glaucoma with mild, moderate or severe damage and / or with intraocular hypertension users of Krytantek Ofteno® at least two previous months and are under control Of the corresponding IOP target.

a study group A or B will be randomly assigned, in group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be evaluated again and switched from therapy to solution PRO-122 which will be used for 30 days until the 60th day, date of the final visit.

In the case of those assigned to group B on day 1, the change to PRO-122 solution will be made for 30 continuous days until the date of revision on day 30, the day on which treatment with Krytantek Ofteno® will be restored to continue until the Day 60 for the final evaluation.

The selected subjects will be observed for 60 days.

• Masking: Double (Participant, Investigator)

Masking Description

Masking will be carried out using identical boxes in the primary package in both groups.

Blinding for the research subject and the investigator will be carried out by using labels containing the assignation number, which will replace the original labels in the case of the comparator. Due to the nature of the primary containers of the research products, single-dose vials and multidose bottle, it is not possible to use identical labels.

• Primary Purpose: Treatment
• Official Title: Clinical Study to Evaluate the Non-inferiority of PRO-122 an Ophthlamic Solution Manufactured by Laboratorios Sophia, Previous Treatment With Krytantek Ofteno ®, in Subjects With Primary Open-Angle Glaucoma or Ocular Hypertension.
• Actual Study Start Date: April 1, 2016
• Actual Primary Completion Date: March 1, 2017
• Actual Study Completion Date: June 18, 2017

Arms and Interventions

Arm	Intervention/treatment
Group A; In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit.	Drug: PRO-122; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Name: timolol, dorzolamide, brimonidine; Drug: Krytantek Ofteno®; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Name: timolol, dorzolamide, brimonidine
Group B; In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit.	Drug: PRO-122; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Name: timolol, dorzolamide, brimonidine; Drug: Krytantek Ofteno®; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Name: timolol, dorzolamide, brimonidine

Outcome Measures

Primary Outcome Measures :

1. Intraocular Pressure (IOP) [ Time Frame: Change from Baseline intraocular pressure at day 30 and 60. ]

   Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg.

   The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60).

Secondary Outcome Measures :

1. Visual Acuity (VA) [ Time Frame: Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]

   The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing "normal" acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less.

   Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated.

Other Outcome Measures:

1. Adverse Events [ Time Frame: 75 days, includes the security call ]
   The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent.
2. Conjunctival Hyperemia [ Time Frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]
   the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
3. Chemosis [ Time Frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]
   Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
4. Eye Burning [ Time Frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]
   Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported.
5. Number of Eyes With Tearing [ Time Frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]
   Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported
6. Number of Eyes With Foreign Body Sensation [ Time Frame: Baseline (day 1) crossover visit (day 30) and final visit (day 60) ]
   Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18 years of age or older
• male or female.
• obtained in the external consultation.
• With diagnosis primary of open-angle glaucoma and / or hypertension classified as mild, moderate or severe glaucomatous damage, users of Krytantek Ofteno® at least two months prior to inclusion and under control of the target IOP.
• informed consent.

Exclusion Criteria:

General Criteria

1. Subjects with topical or systemic medication that interferes decisively in the results of the study. (Such as topical immunomodulators, lacrimal point tamponade, corticosteroids, ocular hypotensives other than those listed above, artificial tears with preservative).
2. Subjects (female) with an active sex life who are not using a contraceptive method.
3. Female Subjects in pregnancy or breastfeeding.
4. Female subjects with positive urine pregnancy test.
5. Positive drug addiction (verbal interrogation).
6. Subjects who have participated in any clinical research study in the last 40 days.
7. Legally or mentally disabled subjects to give informed consent for their participation in this study.
8. Subjects who can not comply with the appointments or with all the requirements of the protocol.

Ophthalmologic criteria

1. Subject with only one eye with vision.
2. Subjects with visual capacity 20/200 or worse.
3. Subjects with a narrow-angle history without treatment, with or without total or partial closure of the angle in either eye.
4. Subjects with corneal abnormalities that prevent applanation tonometry.
5. Subjects with ocular surgery or ocular trauma 6 months prior to inclusion.
6. Any ocular laser surgery 3 months prior.
7. Any uncontrolled or progressive retinal disease.
8. Inflammatory diseases of any kind.
9. Contact lens wearers.
10. Subjects with a history of hypersensitivity to any of the ingredients of the research product or its analogues.

Contacts and Locations

No Contacts or Locations Provided

  Study Documents (Full-Text)

Documents provided by Laboratorios Sophia S.A de C.V.:

Study Protocol and Statistical Analysis Plan  [PDF] March 1, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gomez-Aguayo F, Paczka JA, Lenero-Cordova R, Jimenez-Roman J, Davila-Villarreal J, Hartleben C, Baiza-Duran L, Olvera-Montano O, Garcia-Velez F, Munoz-Villegas P. A Phase III Randomized Clinical Trial of a 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination, Preservative-Free Ophthalmic Solution vs. 0.5% Timolol + 0.2% Brimonidine + 2.0% Dorzolamide Fixed Combination in Patients with Controlled Primary Open-Angle Glaucoma. Ophthalmol Ther. 2018 Jun;7(1):145-156. doi: 10.1007/s40123-018-0128-8. Epub 2018 Apr 21.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT03257813
• Other Study ID Numbers: SOPH122-0914/III
• First Posted: August 22, 2017
• Results First Posted: December 9, 2019
• Last Update Posted: December 9, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Confidentiality Policy

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Laboratorios Sophia S.A de C.V.:

timolol; dorzolamide; brimonidine; Glaucoma; Ocular hypertension

Additional relevant MeSH terms:

Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Eye Diseases; Timolol; Brimonidine Tartrate; Dorzolamide; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors