Postoperative Ocular Pain After PRK Surgery
Conditions
Keywords
ocular pain, photorefractive keratectomy (PRK), SAF312, corneal epithelial defect
Brief summary
The purpose of this study is to determine if SAF312 eye drops have an adequate safety and efficacy profile to justify further clinical development for the treatment of ocular pain associated with corneal epithelial defect such as after photorefractive keratectomy (PRK) surgery
Interventions
DRUGSAF312
DRUGPlacebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Normal eye exam except for refractive error at baseline. * Myopia should not exceed -4.00 Diopters (sphere) and 3.00 diopters of astigmatism, with spherical equivalent not higher than -4.50, confirmed by manifest refraction at baseline.
Exclusion criteria
* Monocular patient (including amblyopia) or best corrected visual acuity score worse than 20/80 (Snellen) or 55 letters (EDTRS), at baseline. * Any systemic or ocular disease that might affect wound healing (such as severe rheumatoid arthritis or diabetes or history of keloid formation) or a history of ocular trauma, uveitis, infection, or inflammation in the 6 months prior to baseline. * Previous refractive or corneal surgery (such as LASIK, PRK, radial keratotomy, pterygium removal, corneal transplantation). * Chronic pain of any etiology or any significant illness which has not resolved within two (2) weeks prior to initial dosing. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pre-dose Pain Assessment | 6 hours | VAS pain severity scale pre-dose, 6 hours post-operatively. The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain |
| Average Ocular Pain VAS Assessments | 12 hours | VAS pain severity scale from the first post-operative assessment to pre-dose 12 hours post-operative assesment The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 6,12, 24, 48 and 72 hours post-operatievly | Summary of oral rescue medication use incidence (number of patients who DID NOT use oral rescue medication) |
| VAS Pain Assessments | 72 hours | VAS pain assessment during the first 72 hours post-operatively. VAS pain severity scale from the first post-operative assessment to pre-dose 12 hours post-operative assesment The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain |
| Plasma Concentration of SAF312 | day1, day 4 | C Max |
Countries
United States
Participant flow
Recruitment details
A total of 40 patients were randomized in a 1:1 ratio to two treatment sequences: SAF312 followed by Vehicle, or Vehicle followed by SAF312.
Pre-assignment details
Bilateral crossover design: A crossover design was utilized in order to decrease the inter-patient variability due to different pain tolerance in different individuals.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1 Vehicle/SAF312 | 20 |
| Treatment Sequence 2 SAF312 / Vehicle | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Treatment Sequence 1 | Treatment Sequence 2 | Total |
|---|---|---|---|
| Age, Continuous | 34.4 years STANDARD_DEVIATION 10.77 | 33.7 years STANDARD_DEVIATION 8.94 | 34.0 years STANDARD_DEVIATION 9.78 |
| Race/Ethnicity, Customized asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized hispanic latino | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized multiple | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized non hispanic latino | 19 Participants | 18 Participants | 37 Participants |
| Race/Ethnicity, Customized white | 18 Participants | 17 Participants | 35 Participants |
| Sex/Gender, Customized female | 9 Participants | 10 Participants | 19 Participants |
| Sex/Gender, Customized male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 8 / 40 | 5 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Average Ocular Pain VAS Assessments
VAS pain severity scale from the first post-operative assessment to pre-dose 12 hours post-operative assesment The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain
Time frame: 12 hours
Population: Primary PD Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAF312 | Average Ocular Pain VAS Assessments | 30.90 score on a scale | Standard Error 4.07 |
| Vehicle | Average Ocular Pain VAS Assessments | 39.47 score on a scale | Standard Error 4.11 |
p-value: 0.01790% CI: [-14.29, -2.83]Kenward-Roger method
Primary
Visual Analog Scale (VAS) Pre-dose Pain Assessment
VAS pain severity scale pre-dose, 6 hours post-operatively. The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain
Time frame: 6 hours
Population: Primary PD Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAF312 | Visual Analog Scale (VAS) Pre-dose Pain Assessment | 34.63 score on a scale | Standard Error 4.05 |
| Vehicle | Visual Analog Scale (VAS) Pre-dose Pain Assessment | 45.76 score on a scale | Standard Error 4.1 |
p-value: 0.00590% CI: [-17.54, -4.71]Kenward-Roger method
Secondary
Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication)
Summary of oral rescue medication use incidence (number of patients who DID NOT use oral rescue medication)
Time frame: 6,12, 24, 48 and 72 hours post-operatievly
Population: Secondary PD analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAF312 | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-12 hours post-operatively | 19 Participants |
| SAF312 | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-48 hours post-operatively | 11 Participants |
| SAF312 | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-24 hours post-operatively | 16 Participants |
| SAF312 | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-72 hours post-operatively | 11 Participants |
| SAF312 | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-6 hours post-operatively | 23 Participants |
| Vehicle | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-72 hours post-operatively | 11 Participants |
| Vehicle | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-6 hours post-operatively | 19 Participants |
| Vehicle | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-12 hours post-operatively | 16 Participants |
| Vehicle | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-24 hours post-operatively | 12 Participants |
| Vehicle | Incidence of and Amount of Rescue Oral Analgesics (Number of Participants Who Did Not Use Oral Rescue Medication) | 0-48 hours post-operatively | 11 Participants |
Secondary
Plasma Concentration of SAF312
C Max
Time frame: day1, day 4
Population: PK Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAF312 | Plasma Concentration of SAF312 | day 1 | 0.454 ng/mL | Standard Deviation 0.227 |
| SAF312 | Plasma Concentration of SAF312 | day 4 | 2.40 ng/mL | Standard Deviation 1.53 |
Secondary
VAS Pain Assessments
VAS pain assessment during the first 72 hours post-operatively. VAS pain severity scale from the first post-operative assessment to pre-dose 12 hours post-operative assesment The Visual Analog Scale (VAS) is a commonly used measurement of pain, discomfort, that goes from 0 meaning no pain to 100 meaning worst imaginable pain
Time frame: 72 hours
Population: Primary PD Analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAF312 | VAS Pain Assessments | 5.13 score on a scale | Standard Error 4.05 |
| Vehicle | VAS Pain Assessments | 3.58 score on a scale | Standard Error 4.1 |