A Dose-ranging Study to Evaluate the Safety and Efficacy of UNR844 in Subjects With Presbyopia.

Study Overview
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Brief Summary
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Study of safety and efficacy of UNR844 in subjects with presbyopia.

Detailed Description
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This was a randomized, placebo-controlled, double-masked,multi-arm, parallel-group, multi-center 13-month study which consisted of: A 1 week run-in period A 3-month treatment course with UNR844 and/or Placebo A 9-month treatment holiday period Participants were randomized equally to one of five treatment arms: UNR844 5 mg/mL,UNR844 13.3 mg/mL, UNR844 23 mg/mL, UNR844 30 mg/mL, or Placebo eye drops twice-a-day for three months. Participants underwent a 1 week run-in period where they were assessed for entry criteria during the Screening visit. During the run-in period, participants self-administered 1 drop of artificial tears twice-a-day (1 drop in the morning and 1 drop in the evening) in each eye at home. This run-in period was designed to help minimize any potential variability in distance corrected near visual acuity (DCNVA) caused due to initial ocular surface issues and help to establish an accurate baseline prior to randomization. The run-in period was to help exclude participants with a change in DCNVA of 0.10 logMAR difference between Screening and Baseline. This study was conducted to determine the optimum dose of UNR844 treatment and the duration of effect of UNR844 treatment for further development.

Official Title
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A Randomized, Placebo-controlled, Double-masked, Multi-center, Dose-ranging Study to Evaluate the Safety, and Efficacy of UNR844 in Subjects With Presbyopia

Conditions
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Presbyopia

Intervention / Treatment
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* Drug: UNR844
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed Impaired near vision in each eye and when using both eyes, without any near correction Need a certain level of near correction Exclusion Criteria: Impaired distance vision in either eye, with distance correction (if any) Severe short- or long-sightedness Any significant medical or clinical conditions affecting vision, the eyes or general health

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UNR844 5 mg/mL<br>UNR844 5 mg/mL ophthalmic solution; one drop twice-a-day for three months | Drug: UNR844<br>* Ophthalmic solution for topical ocular administration<br>* Other names: EV06;|
| Experimental: UNR844 13.3 mg/mL<br>UNR844 13.3 mg/mL 1 ophthalmic solution; one drop twice-a-day for three months | Drug: UNR844<br>* Ophthalmic solution for topical ocular administration<br>* Other names: EV06;|
| Experimental: UNR844 23 mg/mL<br>UNR844 23 mg/mL ophthalmic solution; one drop twice-a-day for three months | Drug: UNR844<br>* Ophthalmic solution for topical ocular administration<br>* Other names: EV06;|
| Experimental: UNR844 30 mg/mL<br>UNR844 30 mg/mL ophthalmic solution; one drop twice-a-day for three months | Drug: UNR844<br>* Ophthalmic solution for topical ocular administration<br>* Other names: EV06;|
| Placebo Comparator: Placebo Ophthalmic Solution<br>placebo ophthalmic solution; one drop twice-a-day for three months | Drug: Placebo<br>* Placebo<br>* Other names: Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize Dose-response of UNR844 for Change From Baseline in Binocular Distance-corrected Near Visual Acuity (DCNVA) at Month 3 | Characterize dose response of UNR844 as measured by change from baseline at Month 3 in binocular DCNVA (without near correction) in Logarithm of Minimum Angle of Resolution (logMAR), at 40cm. A low logMAR score represents good vision while a high logMAR score represents bad vision. | Baseline, Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize Dose Response of UNR844 as Measured by Change From Baseline in Monocular (Worse-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) at Month 3 | Characterize dose response of UNR844 as measured by change from baseline at Month 3 in monocular (worse-seeing eye) DCNVA in Logarithm of Minimum Angle of Resolution (logMAR), at 40 cm. A low logMAR score represents good vision while a high logMAR score represents bad vision. | Baseline, Month 3 | 
| Characterize Dose Response of UNR844 as Measured by Change From Baseline in Monocular (Better-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) at Month 3 | Characterize dose response of UNR844 as measured by change from baseline at Month 3 in monocular (better-seeing eye) DCNVA in Logarithm of Minimum Angle of Resolution (logMAR), at 40cm. A low logMAR score represents good vision while a high logMAR score represents bad vision. | Baseline, Month 3 | 
| Percentage of Participants Gaining at Least 0.30 logMAR in Binocular Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3 | Percentage of participants gaining at least 0.3 logMAR in binocular DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines. | Baseline, Month 3 | 
| Percentage of Participants Gaining at Least 0.30 logMAR in Monocular (Worse-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3 | Percentage of participants gaining at least 0.3 logMAR in monocular (worse-seeing eye) DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines. | Baseline, Month 3 | 
| Percentage of Participants Gaining at Least 0.30 logMAR in Monocular (Better-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3 | Percentage of participants gaining at least 0.3 logMAR in monocular (better-seeing eye) DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines. | Baseline, Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lens, loss of elasticity in lens, lens disorder, loss of near vision, Presbyopia, UNR844, farsightedness