Laser In Situ Keratomileusis
Conditions
Brief summary
This study will evaluate the safety and efficacy of Cyclosporine 0.005% and 0.010% eye drops administered twice daily before and following LASIK surgery.
Interventions
DRUGCyclosporine 0.010% eye drops
Cyclosporine 0.010% eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery.
DRUGCyclosporine 0.005% eye drops
Cyclosporine 0.005% eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery.
DRUGPlacebo (Vehicle for Cyclosporine)
Placebo eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patient is scheduled for bilateral LASIK surgery * Patient is in good general health * Eye glasses prescription of -1 to -8
Exclusion criteria
* Significant Dry Eye * Presence of eye disease * Uncontrolled systemic disease * Previous use of RESTASIS®
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cure | 6 Months | Time to cure is defined as the number of days after laser in situ keratomileusis (LASIK) surgery that the patient has corneal sensitivity (the capability of the cornea to respond to stimulation) ≥ 50 millimeters in all 9 regions of both eyes after LASIK surgery. A patient is considered cured at the first of 2 consecutive visits meeting these criteria. The Inter-Quartile Range presented is actually the 25th Quantile and the 75th Quantile obtained from the Kaplan-Meier Model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Worst Outcome Post-LASIK Surgery in Tear Film Assessment | Months 3 to 6 | The time to the worst outcome post-LASIK surgery in tear film stability is assessed using the Ocular Scatter Index (OSI). The OSI is calculated by an instrument which takes images of the eye over time. OSI values ≥3.0 indicate lower tear film quality resulting in a loss of visual acuity. The worst outcome post-LASIK surgery is defined as the shortest time to OSI ≥3 across both eyes and post-LASIK surgery months 3 to 6. |
| Percentage of Patients With Cumulative Poor Vision | Month 3, Month 4, Month 5, Month 6 | Cumulative Poor Vision is determined binocularly per patient (using both eyes at the same time) from the Poor Vision question on the Ocular Surface Disease Index (OSDI) questionnaire. Severity of poor vision is graded on a 5-point scale (0 = none of the time, 1 = some of the time, 2 = half of the time, 3 = most of the time, 4 = all of the time). Cumulative poor vision is defined as at least one poor vision score ≥ 1 beginning at Month 3 post-LASIK. |
| Worst Outcome Post-LASIK Surgery in Reading Speed Assessment | Months 3 to 6 | Reading speed is determined using the MNREAD™ Reading Card. The MNREAD™ reading card is designed to simulate a normal every day reading scenario using binocular vision (both eyes at the same time). The MNREAD™ Reading speed is calculated as (60) X \[Number of words on card - (reading errors)\]/ (number of seconds until the card is read). The worst outcome is defined as the smallest number of words per minute across post-LASIK surgery months 3 to 6. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine 0.010% Eye Drops Cyclosporine 0.010% eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery. | 207 |
| Cyclosporine 0.005% Eye Drops Cyclosporine 0.005% eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery. | 209 |
| Placebo (Vehicle for Cyclosporine) Placebo eye drops administered as 1 drop to each eye twice daily (morning and evening) for at least 2 weeks prior to LASIK surgery and up to 7 months post-LASIK surgery. | 205 |
| Total | 621 |
Baseline characteristics
| Characteristic | Total | Cyclosporine 0.010% Eye Drops | Cyclosporine 0.005% Eye Drops | Placebo (Vehicle for Cyclosporine) |
|---|---|---|---|---|
| Age, Customized 30 to 40 years | 299 Participants | 110 Participants | 97 Participants | 92 Participants |
| Age, Customized <30 years | 214 Participants | 68 Participants | 69 Participants | 77 Participants |
| Age, Customized >40 years | 108 Participants | 29 Participants | 43 Participants | 36 Participants |
| Sex: Female, Male Female | 338 Participants | 115 Participants | 118 Participants | 105 Participants |
| Sex: Female, Male Male | 283 Participants | 92 Participants | 91 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 78 / 207 | 66 / 209 | 66 / 205 |
| serious Total, serious adverse events | 2 / 207 | 0 / 209 | 3 / 205 |
Outcome results
Primary
Time to Cure
Time to cure is defined as the number of days after laser in situ keratomileusis (LASIK) surgery that the patient has corneal sensitivity (the capability of the cornea to respond to stimulation) ≥ 50 millimeters in all 9 regions of both eyes after LASIK surgery. A patient is considered cured at the first of 2 consecutive visits meeting these criteria. The Inter-Quartile Range presented is actually the 25th Quantile and the 75th Quantile obtained from the Kaplan-Meier Model.
Time frame: 6 Months
Population: Modified Intent to Treat: all randomized and treated patients with both eyes having Post-LASIK surgery and corneal sensitivity measurements of \< 25 mm in the 3 central regions at Post-Surgery Week 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cyclosporine 0.010% Eye Drops | Time to Cure | 189.0 Days |
| Cyclosporine 0.005% Eye Drops | Time to Cure | 194.0 Days |
| Placebo (Vehicle for Cyclosporine) | Time to Cure | 189.0 Days |
Secondary
Percentage of Patients With Cumulative Poor Vision
Cumulative Poor Vision is determined binocularly per patient (using both eyes at the same time) from the Poor Vision question on the Ocular Surface Disease Index (OSDI) questionnaire. Severity of poor vision is graded on a 5-point scale (0 = none of the time, 1 = some of the time, 2 = half of the time, 3 = most of the time, 4 = all of the time). Cumulative poor vision is defined as at least one poor vision score ≥ 1 beginning at Month 3 post-LASIK.
Time frame: Month 3, Month 4, Month 5, Month 6
Population: Intent to treat: all randomized patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine 0.010% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 3 | 15.0 Percentage of Patients |
| Cyclosporine 0.010% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 4 | 17.9 Percentage of Patients |
| Cyclosporine 0.010% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 5 | 21.7 Percentage of Patients |
| Cyclosporine 0.010% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 6 | 23.7 Percentage of Patients |
| Cyclosporine 0.005% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 6 | 26.8 Percentage of Patients |
| Cyclosporine 0.005% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 3 | 18.7 Percentage of Patients |
| Cyclosporine 0.005% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 5 | 26.3 Percentage of Patients |
| Cyclosporine 0.005% Eye Drops | Percentage of Patients With Cumulative Poor Vision | Month 4 | 22.5 Percentage of Patients |
| Placebo (Vehicle for Cyclosporine) | Percentage of Patients With Cumulative Poor Vision | Month 6 | 26.3 Percentage of Patients |
| Placebo (Vehicle for Cyclosporine) | Percentage of Patients With Cumulative Poor Vision | Month 4 | 23.9 Percentage of Patients |
| Placebo (Vehicle for Cyclosporine) | Percentage of Patients With Cumulative Poor Vision | Month 5 | 24.9 Percentage of Patients |
| Placebo (Vehicle for Cyclosporine) | Percentage of Patients With Cumulative Poor Vision | Month 3 | 19.0 Percentage of Patients |
Secondary
Time to Worst Outcome Post-LASIK Surgery in Tear Film Assessment
The time to the worst outcome post-LASIK surgery in tear film stability is assessed using the Ocular Scatter Index (OSI). The OSI is calculated by an instrument which takes images of the eye over time. OSI values ≥3.0 indicate lower tear film quality resulting in a loss of visual acuity. The worst outcome post-LASIK surgery is defined as the shortest time to OSI ≥3 across both eyes and post-LASIK surgery months 3 to 6.
Time frame: Months 3 to 6
Population: Intent to Treat population: all randomized patients for whom data are available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporine 0.010% Eye Drops | Time to Worst Outcome Post-LASIK Surgery in Tear Film Assessment | 11.2 Seconds | Standard Deviation 4.24 |
| Cyclosporine 0.005% Eye Drops | Time to Worst Outcome Post-LASIK Surgery in Tear Film Assessment | 12.0 Seconds | Standard Deviation 4.51 |
| Placebo (Vehicle for Cyclosporine) | Time to Worst Outcome Post-LASIK Surgery in Tear Film Assessment | 11.5 Seconds | Standard Deviation 4.39 |
Secondary
Worst Outcome Post-LASIK Surgery in Reading Speed Assessment
Reading speed is determined using the MNREAD™ Reading Card. The MNREAD™ reading card is designed to simulate a normal every day reading scenario using binocular vision (both eyes at the same time). The MNREAD™ Reading speed is calculated as (60) X \[Number of words on card - (reading errors)\]/ (number of seconds until the card is read). The worst outcome is defined as the smallest number of words per minute across post-LASIK surgery months 3 to 6.
Time frame: Months 3 to 6
Population: Intent to Treat population: all randomized patients for whom data are available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporine 0.010% Eye Drops | Worst Outcome Post-LASIK Surgery in Reading Speed Assessment | 173.0 Words Per Minute (WPM) | Standard Deviation 40.17 |
| Cyclosporine 0.005% Eye Drops | Worst Outcome Post-LASIK Surgery in Reading Speed Assessment | 173.7 Words Per Minute (WPM) | Standard Deviation 42.18 |
| Placebo (Vehicle for Cyclosporine) | Worst Outcome Post-LASIK Surgery in Reading Speed Assessment | 167.4 Words Per Minute (WPM) | Standard Deviation 45.21 |