24-hour Efficacy and Tolerability of the Tafluprost-timolol Fixed Association Without Preservatives in Glaucomatous or Ocular Hypertensive Patients Already Treated With Latanoprost Preserved With BAK. A Prospective, Open Study of 3 Months Duration.

Study Overview
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Brief Summary
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This is a phase IV, interventional, multi-center, open clinical Trial. Patients will be administered one eye drop of tafluprost/timolol fixed combination at 20:00 (+/- 1 hour), in the treatment of open angle glaucoma and ocular hypertension. The patients will suspend the treatment with latanoprost.

Detailed Description
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This is a phase IV, interventional, multi-center, not comparative, open clinical Trial to evaluate the effectiveness in reducing the mean 24-hour IOP of the preservative-free fixed combination of Tafluprost 0.0015% and Timolol 0.5% administered once at night (8pm) in POAG or OHT patients suffering from mild OSD and requiring further IOP reduction while in topical treatment with BAK-preserved Latanoprost 0.05 mg/ml. Three Italian recruiting centers are included in the study and the estimated number of patients to be enrolled is 43. After evaluating the patient's eligibility, the patients will suspend the treatment with latanoprost and will be administered one eye drop of tafluprost/timolol fixed combination at 20:00 (+/- 1 hour) at the end of the V1B visit. Active drug will be contained (about 30 µl, one drop) contains about 0.45 micrograms of tafluprost and 0.15 mg of timolol. The Study consists in 6 Visits: Screening visit V0 and baseline V1A. Treatment period visit V1B; V2; V3A; V3B. End of study V3B.

Official Title
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24-hour Efficacy and Tolerability of the Tafluprost-timolol Fixed Association Without Preservatives in Glaucomatous or Ocular Hypertensive Patients Already Treated With Latanoprost Preserved With BAK. A Prospective, Open Study of 3 Months Duration.

Conditions
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Glaucoma, Open-Angle, Ocular Hypertension

Intervention / Treatment
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* Drug: tafluprost/timolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ocular hypertension or primary open-angle glaucoma or secondary to dispersion of pigment or pseudoesfoliatio; IOP <22 mmHg in latanoprost therapy in both eyes since at least 6 weeks and > 17 mmHg in at least one eye; OSD at least mild as defined by DEQ-5 (score> 6); Examination of the visual field during the three months prior to enrollment (if not present, the patient must be subjected to a visual field at the screening visit); Treatment with latanoprost BAK-preserved from at least 6 weeks; Subject agrees to follow the study procedures and signs the EC-approved ICF; For women of child-bearing potential, blood screening for beta-HCG before randomization and use of one effective method of birth control during the conduct of the study Exclusion Criteria: Inability to understand and sign informed consent; Age under 18 years; Other forms of secondary glaucoma (besides pigmentary and pseudoesfoliatius); Narrow angle or history of acute glaucoma attacks; Previous history of trabeculoplasty in the previous 6 months; History of glaucoma surgery or refractive surgery; Cataract surgery in the 6 months prior to enrollment; Contraindications to the use of beta-blockers (reactive airway disease, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease; sinus bradycardia, sick sinus syndrome, including sinoatrial block, second or third degree atrioventricular block not controlled by pacemaker; full-blown heart failure, cardiogenic shock); Damage to the visual field with a mean deviation (MD) <-20 dB; BCVA <2/10; Topical ocular drugs performed within 3 months prior to enrollment that may interfere with the study results (eg steroids, non-steroidal anti-inflammatory drugs, immunosuppressants, etc.); Use of tear substitutes containing preservatives within 30 days prior to enrollment; Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study or would impair interpretation of results; Corneal anomalies that preclude an accurate measurement of IOP (eg astigmatism> 3 D, keratoconus, opacity or corneal ulcers); Any type of previous corneal or conjunctival surgery including pterygium removal or refractive surgery; Unstable systemic disorders that may require the initiation or variation of therapies that may influence intraocular pressure during the study; Woman of childbearing potential, or who is currently pregnant or breastfeeding; Inability to adhere to the procedures required by the protocol or to the studio treatment; Participation in another experimental therapeutic protocol within one month prior to baseline and during the study period (participation in natural history study is allowed); Hypersensitivity to the active substances or to any of the excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Single group, open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tafluprost/timolol<br>Enrolled patients will be treated with one drop of the fixed combination Tafluprost-Thymol without preservative in the evening at 20.00 (+/- 1 hour). Patients will be administrered with one drop in the conjunctival sac of the affected eye (s) once a day. | Drug: tafluprost/timolol<br>* One ml active drug contains: 15 micrograms of tafluprost and 5 mg of timolol (as maleate). A single-dose container (0.3 ml) of eye drops, solution, contains 4.5 micrograms of tafluprost and 1.5 mg of timolol. One drop (about 30 µl) contains about 0.45 micrograms of tafluprost and 0.15 mg of timolol. Patients will be administrered with one drop in the conjunctival sac of the affected eye (s) once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evaluation of the mean 24-h absolute Intraocular Pressure (IOP) | Reduction measured in mmHg (millimeters of mercury). | through study completion, an average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the average reduction of Intraocular Pressure(IOP) at 24-hour | Curve measured in mmHg. | through study completion, an average of 3 months | 
| Evaluation of the percentage reduction of the average Intraocular Pressure(IOP) of the 24 hours | percentage at each time point. | through study completion, an average of 3 months | 
| Evaluation of the average daytime reduction and night of the Intraocular Pressure(IOP) | Measured in mmHg | through study completion, an average of 3 months | 
| Evaluation of the percentage of patients achieving Intraocular Pressure(IOP) reduction in average | reductions in average IOP at 24h when plus 20%, when plus 25%,when plus 30%. | through study completion, an average of 3 months | 
| Evaluation of the changes in the Corneale Staining Test (CFS) and Break-up Time Test (tBUT) parameters | with fluorescein, measured area and density | through study completion, an average of 3 months | 
| Evaluation of the changes in Dry Eye Questionnaire (DEQ-5) | DEQ-5 questionnaire Score | through study completion, an average of 3 months | 
| Evaluation of the changes of the number, activation of corneal, conjunctival dendritic cells to confocal microscopy. | Changes number corneal and dendritic cells | through study completion, an average of 3 months | 
| Evaluation of the changes of the number of conjunctival goblet cells to confocal microscopy | Changes of number of goblet cells | through study completion, an average of 3 months | 
| Evaluation of the changes in quality of life | NEIVFQ-25 questionnaire (score). | through study completion, an average of 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glaucoma, ocular hypertension