Presbyopia
Conditions
Brief summary
This is a 4-visit, multi-center, randomized, double-masked, parallel group study evaluating the safety and efficacy of CSF-1 in the treatment of presbyopia.
Detailed description
This is a 4-visit, multi-center, randomized, double-masked, parallel group study evaluating the safety and efficacy of CSF-1 in the treatment of presbyopia. Approximately 150 subjects will be enrolled across 7 study centers in the United States. At Visit 2, subjects will be randomized 1:1:1 to one of three treatment arms: CSF-1, CSF-1 Component #1, or CSF-1 Component #2. All subjects will dose twice a day in both eyes with a single drop of their assigned treatment for approximately 1 week. At Visit 3, subjects randomized to CSF-1 will now receive a different concentration of CSF-1, subjects randomized to CSF-1 Component #1 will receive a different concentration of CSF-1 Component #1 and subjects randomized to CSF-1 Component #2 will continue dosing with the same concentration of CSF-1 Component #2. All subjects will continue dosing twice a day in both eyes for approximately 1 week.
Interventions
DRUGCSF-1
This treatment arm consists of 2 different concentrations of CSF-1. Subjects randomized to the CSF-1 treatment arm will receive their first dose of CSF-1 in-office at Visit 2. All subjects will dose twice a day in both eyes with a single drop for approximately 1 week. At Visit 3, subjects randomized to the CSF-1 arm will now receive a different concentration of CSF-1. Subjects will continue dosing twice a day in both eyes for approximately 1 week.
DRUGCSF-1 Component #1
This treatment arm consists of 2 different concentrations of CSF-1 Component #1. Subjects randomized to the CSF-1 Component #1 treatment arm will receive their first dose of CSF-1 Component #1 in-office at Visit 2. All subjects will dose twice a day in both eyes with a single drop for approximately 1 week. At Visit 3, subjects randomized to the CSF-1 Component #1 arm will now receive a different concentration of CSF-1 Component #1. Subjects will continue dosing twice a day in both eyes for approximately 1 week.
DRUGCSF-1 Component #2
This treatment arm consists of a single concentration of CSF-1 Component #2. Subjects randomized to the CSF-1 Component #2 treatment arm will receive their first dose of CSF-1 Component #2 in-office at Visit 2. All subjects will dose twice a day in both eyes with a single drop for approximately 1 week. At Visit 3, subjects randomized to the CSF-1 Component #2 arm will continue dosing with the same concentration of CSF-1 Component #2. Subjects will continue dosing twice a day in both eyes for approximately 1 week.
Sponsors
Orasis Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must: 1. Have presbyopia
Exclusion criteria
* Subjects must not: 1. Have any contraindications to the study medications or diagnoses that would confound the study data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With ≥ 3 Lines Gain in Near Best Distance Corrected Visual Acuity (BDCVA) (at 40 cm) | 1 hour post dose on day 8 | Number of subjects with a ≥ 3-line gain in near BDCVA (at 40 cm) at 1 hour post dose after 1 week treatment with CSF-1-Fixed Dose Combination (FDC) low dose (pilocarpine HCl 0.2% + diclofenac 0.006%) or pilocarpine HCl 0.2% alone or diclofenac 0.006% alone |
| Number of Subjects With ≥ 3 Lines Gain in BDCVA (at 40 cm) | 1 hour post dose on day 15 | Number of subjects with a ≥ 3-line gain in near BDCVA (at 40 cm) at 1 hour post dose after 1 week treatment with CSF-1-FDC (pilocarpine HCl 0.4% + diclofenac 0.006%) or pilocarpine HCl 0.4% alone or diclofenac 0.006% alone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 1 hour post dose on day 8 | Number of subjects with a ≥ 2-line gain in near BDCVA (at 40 cm0 at 1 hour post dose after 1 week treatment with CSF-1-FDC (pilocarpine HCl 0.2% + diclofenac 0.006%) or pilocarpine HCl 0.2% alone or diclofenac 0.006% alone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CSF-1-FDC pilocarpine HCl + diclofenac Na (fixed dose combination) | 53 |
| Pilo pilocarpine HCl (alone) | 55 |
| Diclo diclofenac Na (serves as control group) | 58 |
| Total | 166 |
Baseline characteristics
| Characteristic | CSF-1-FDC | Total | Diclo | Pilo |
|---|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 3.96 | 54.6 years STANDARD_DEVIATION 4.63 | 54.1 years STANDARD_DEVIATION 4.94 | 54.9 years STANDARD_DEVIATION 4.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 162 Participants | 56 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 26 Participants | 7 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 134 Participants | 48 Participants | 45 Participants |
| Region of Enrollment United States | 53 participants | 166 participants | 58 participants | 55 participants |
| Sex: Female, Male Female | 30 Participants | 102 Participants | 33 Participants | 39 Participants |
| Sex: Female, Male Male | 23 Participants | 64 Participants | 25 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 1 / 55 | 0 / 58 |
| other Total, other adverse events | 10 / 53 | 13 / 55 | 6 / 58 |
| serious Total, serious adverse events | 0 / 53 | 1 / 55 | 0 / 58 |
Outcome results
Primary
Number of Subjects With ≥ 3 Lines Gain in BDCVA (at 40 cm)
Number of subjects with a ≥ 3-line gain in near BDCVA (at 40 cm) at 1 hour post dose after 1 week treatment with CSF-1-FDC (pilocarpine HCl 0.4% + diclofenac 0.006%) or pilocarpine HCl 0.4% alone or diclofenac 0.006% alone
Time frame: 1 hour post dose on day 15
Population: The primary analysis was conducted on the per protocol (PP) study population set and therefore the number of subjects is slightly different than from the overall participants flow.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSF-1-FDC | Number of Subjects With ≥ 3 Lines Gain in BDCVA (at 40 cm) | 22 Participants |
| Pilo | Number of Subjects With ≥ 3 Lines Gain in BDCVA (at 40 cm) | 23 Participants |
| Diclo | Number of Subjects With ≥ 3 Lines Gain in BDCVA (at 40 cm) | 9 Participants |
p-value: 0.001595% CI: [1.646, 8.154]Regression, Logistic
p-value: 0.000295% CI: [2.088, 10.786]Regression, Logistic
Primary
Number of Subjects With ≥ 3 Lines Gain in Near Best Distance Corrected Visual Acuity (BDCVA) (at 40 cm)
Number of subjects with a ≥ 3-line gain in near BDCVA (at 40 cm) at 1 hour post dose after 1 week treatment with CSF-1-Fixed Dose Combination (FDC) low dose (pilocarpine HCl 0.2% + diclofenac 0.006%) or pilocarpine HCl 0.2% alone or diclofenac 0.006% alone
Time frame: 1 hour post dose on day 8
Population: The primary analysis was conducted on the per protocol (PP) study population set and therefore the number of subjects is slightly different than from the overall participant flow.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSF-1-FDC | Number of Subjects With ≥ 3 Lines Gain in Near Best Distance Corrected Visual Acuity (BDCVA) (at 40 cm) | 10 Participants |
| Pilo | Number of Subjects With ≥ 3 Lines Gain in Near Best Distance Corrected Visual Acuity (BDCVA) (at 40 cm) | 12 Participants |
| Diclo | Number of Subjects With ≥ 3 Lines Gain in Near Best Distance Corrected Visual Acuity (BDCVA) (at 40 cm) | 10 Participants |
Comparison: This analysis relates to Day 8 up to when pilocarpine HCl 0.2% either in CSF-1-FDC or as pilocarpine alone was administered for one week.p-value: 0.844595% CI: [0.413, 2.949]Regression, Logistic
p-value: 0.26695% CI: [0.684, 3.958]Regression, Logistic
Secondary
Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm)
Number of subjects with a ≥ 2-line gain in near BDCVA (at 40 cm0 at 1 hour post dose after 1 week treatment with CSF-1-FDC (pilocarpine HCl 0.2% + diclofenac 0.006%) or pilocarpine HCl 0.2% alone or diclofenac 0.006% alone
Time frame: 1 hour post dose on day 8
Population: The analysis was conducted on the per protocol (PP) study population set and therefore the number of subjects is slightly different than from the overall participants flow.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSF-1-FDC | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 24 Participants |
| Pilo | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 25 Participants |
| Diclo | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 18 Participants |
p-value: 0.1145Chi-squared
p-value: 0.0616Chi-squared
Secondary
Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm)
Number of subjects with a ≥ 2-line gain in near BDCVA (at 40 cm) at 1 hour post dose after 1 week treatment with CSF-1-FDC (pilocarpine HCl 0.4% + diclofenac 0.006%) or pilocarpine HCl 0.4% alone or diclofenac 0.006% alone
Time frame: 1 hour post dose on day 15
Population: The analysis was conducted on the per protocol (PP) study population set and therefore the number of subjects is slightly different than from the overall participants flow.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSF-1-FDC | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 35 Participants |
| Pilo | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 39 Participants |
| Diclo | Number of Subjects With ≥ 2 Lines Gain in BDCVA (at 40 cm) | 24 Participants |
p-value: 0.0074Chi-squared
p-value: 0.0001Chi-squared