Presbyopia
Conditions
Keywords
Presbyopia, adults, randomized study, placebo
Brief summary
The purpose of this study was to assess the effect of topical UNR844-Cl (lipoic acid choline ester chloride) ophthalmic solution on near visual function in presbyopic subjects.
Detailed description
This was a multi-center, double-masked, placebo-controlled, randomized, parallel-group study. The total duration of the study was approximately 3 months. Approximately 120 presbyopic subjects were to be enrolled into the study. Presbyopic subjects aged 45 to 55 years were the primary age group in this study. Screening and Baseline: Subjects were screened for eligibility followed by a baseline visit after which they were randomized to receive either UNR844-Cl (1.5%, equivalent to 1.3% freebase) or Placebo, dosed one drop in each eye twice daily, for 3 months. Randomized subjects attended the following study visits after baseline: at Week 2, Month 1, Month 2 and Month 3. The primary objective of this study was to assess the efficacy of UNR844-Cl on binocular distance corrected near visual acuity (DCNVA) in presbyopic subjects aged 45 to 55 years with the primary endpoint being the change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or Placebo treatment. There were two secondary endpoints: 1. To assess the efficacy of UNR844-Cl on achieving 75 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters in binocular DCNVA in presbyopic subjects aged 45 to 55 years with endpoint being the proportion of subjects aged 45 to 55 years achieving 75 or more ETDRS letters in binocular DCNVA at Month 3 after UNR844-Cl or Placebo treatment. 2. To assess the safety of UNR844-Cl in presbyopic subjects by the frequency of treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs) in all subjects after UNR844-Cl or Placebo treatment.
Interventions
DRUGUNR844-Cl
1.5% Ophthalmic solution for topical ocular administration
DRUGPlacebo
placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-mask(Investigator, patient)
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline | Baseline and at Month 3 | Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3 | month 3 | Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision. |
| Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | 4 months | Frequency of treatment emergent adverse events and treatment emergent serious adverse events in all subjects. Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 120 days. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UNR844-Cl 1.5% UNR844-Cl | 62 |
| Placebo Ophthalmic Solution placebo | 62 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Ophthalmic Solution | Total | UNR844-Cl |
|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 5.01 | 54.1 years STANDARD_DEVIATION 4.97 | 53.9 years STANDARD_DEVIATION 4.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 51 Participants | 101 Participants | 50 Participants |
| Sex: Female, Male Female | 41 Participants | 81 Participants | 40 Participants |
| Sex: Female, Male Male | 21 Participants | 43 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 62 | 0 / 124 |
| other Total, other adverse events | 14 / 62 | 5 / 62 | 19 / 124 |
| serious Total, serious adverse events | 0 / 62 | 0 / 62 | 0 / 124 |
Outcome results
Primary
Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline
Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.
Time frame: Baseline and at Month 3
Population: All randomized subjects aged 45 to 55 years at baseline
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| UNR844-Cl | Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline | 6.1 number of letters read correctly | Standard Error 1.24 |
| Placebo Ophthalmic Solution | Change in Binocular Distance-corrected Near Visual Acuity (DCNVA) From Baseline | 4.5 number of letters read correctly | Standard Error 1.27 |
p-value: 0.183290% CI: [-1.34, 4.56]Mixed Models Analysis
Secondary
Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3
Change from baseline in binocular DCNVA in subjects aged 45 to 55 years at Month 3 after UNR844-Cl or placebo treatment. Low contrast (10% contrast) DCNVA at 40 cm is measured binocularly using an electronic visual acuity testing system. This assessment was performed with subjects corrected for any distance refractive errors. The system provided distance-corrected low contrast near visual acuity in an Early Treatment Diabetic Retinopathy Study (ETDRS) letter numerical score. High monocular DCNVA ETDRS letter scores represent good vision; Low monocular DCNVA ETDRS letter scores represent poor vision.
Time frame: month 3
Population: l randomized subjects aged 45 to 55 years at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| UNR844-Cl | Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3 | 10 Participants |
| Placebo Ophthalmic Solution | Number and Percentage of Subjects Aged 45 to 55 Years Achieving 75 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in Binocular DCNVA at Month 3 | 6 Participants |
p-value: 0.28390% CI: [0.72, 4.78]Cochran-Mantel-Haenszel
Secondary
Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation
Frequency of treatment emergent adverse events and treatment emergent serious adverse events in all subjects. Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 120 days.
Time frame: 4 months
Population: All randomized and treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular severe adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular AEs leading to study drug disc. | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any severe adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular AEs leading to study drug disc. | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related adverse events | 4 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any serious adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular adverse events | 11 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular serious adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related ocular adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular serious adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular severe adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related serious adverse events | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related non-ocular adverse events | 4 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related ocular serious AEs | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular adverse events | 4 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related non-ocular serious AEs | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any adverse events leading to study drug disc. | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Death | 0 Participants |
| UNR844-Cl | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any adverse events (AEs) | 14 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Death | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any adverse events (AEs) | 5 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular adverse events | 4 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular adverse events | 2 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any severe adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular severe adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular severe adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related adverse events | 1 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related ocular adverse events | 1 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related non-ocular adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any adverse events leading to study drug disc. | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular AEs leading to study drug disc. | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular AEs leading to study drug disc. | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any serious adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any ocular serious adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any non-ocular serious adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related serious adverse events | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related ocular serious AEs | 0 Participants |
| Placebo Ophthalmic Solution | Number of Subjects With Adverse Events, Ocular Adverse Events, Deaths, Other Serious Adverse Events, or Adverse Events Leading to Study Drug Discontinuation | Any study drug related non-ocular serious AEs | 0 Participants |