Allergic Conjunctivitis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of loteprednol etabonate ophthalmic base, compared to loteprednol etabonate ophthalmic suspension, and vehicle in the prevention of the signs and symptoms of allergic conjunctivitis in a modified Conjunctival Allergen Challenge model and in an environmental model during pollen season. Comparisons will be made following 2 weeks of dosing.
Interventions
DRUGLoteprednol etabonate base (QD)
Loteprednol Etabonate ophthalmic base once daily dosing for 2 weeks
DRUGLoteprednol etabonate base (BID)
Loteprednol etabonate ophthalmic base BID dosing for 2 weeks
DRUGLoteprednol etabonate base (QID)
Loteprednol Etabonate ophthalmic base four times/day dosing for 2 week
DRUGLoteprednol etabonate suspension
Loteprednol etabonate ophthalmic suspension dosed four times daily for 2 weeks.
Vehicle of loteprednol etabonate ophthalmic dosed once, twice or four times daily for 2 weeks.
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive history of ocular allergies and positive skin test reaction to cat hair, cat dander, grasses, ragweed, and/or trees within the past 24 months. * Calculated best-corrected visual acuity of 0.70 logMAR or better in each eye as measured using the ETDRS chart. * Positive bilateral conjunctival allergen challenge(CAC)reaction within 10 minutes of instillation of the last titration of allergen at visit 1. * Positive bilateral CAC reaction in 1 out of 3 time points for the initial and re-challenge at visit 2.
Exclusion criteria
* Known contraindications or sensitivities to the study medication or its components. * Any ocular condition that, in the opinion of the investigator, could affect the subjects safety or trial parameters. * Use of disallowed medications during the period indicated prior to study enrollment or during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Itching | Visit 4 (8 hr re-challenge) | Evaluated by subject at 3, 5, and 7 min post challenge on a scale of 0-4 where 0=no itching and 4=incapacitating itch. |
| Conjunctival Redness | Visit 4 (8 hr re-challenge) | Evaluated by investigator at 7, 15 and 20 minutes post challenge on a scale of 0-4 where 0= no redness and 4=extremely severe redness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Itching | Visit 3 (initial challenge) | Evaluated by the subject at 3, 5 and 7 min post-challenge on a scale of 0-4 where 0=no itching and 4=incapacitating itch. |
| Conjunctival Redness | Visit 3 (initial challenge) | Evaluated by investigator at 7, 15 and 20 minutes post challenge on a scale of 0-4 where 0= no redness and 4=extremely severe redness. |
Countries
United States
Participant flow
Recruitment details
This 2 week ocular allergy study was conducted at 2 ophthalmology clinics in the United States. The first participant was enrolled on 4/22/2010 and the last participant visit was 5/30/2010.
Pre-assignment details
238 participants were screened, a total of 101 participants with seasonal and perennial allergy were randomized into the study. These 101 participants comprised the safety population, 90 of which completed the study. The ITT population was comprised of 97 subjects (4 excluded due to no post CAC-assessment).
Participants by arm
| Arm | Count |
|---|---|
| Loteprednol Etabonate Base (QD) Loteprednol etabonate ophthalmic base dosed once/day. | 21 |
| Loteprednol Etabonate Base (BID) Loteprednol etabonate ophthalmic base dosed two times/day | 20 |
| Loteprednol Etabonate Base (QID) Loteprednol etabonate ophthalmic base dosed four times/day. | 20 |
| Loteprednol Etabonate Suspension (QID) Loteprednol etabonate ophthalmic suspension dosed four times/day | 20 |
| Vehicle of Loteprednol Etabonate Vehicle of loteprednol etabonate, dosed either QD, BID, or QID | 20 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Vehicle of Loteprednol Etabonate | Total | Loteprednol Etabonate Base (QD) | Loteprednol Etabonate Base (BID) | Loteprednol Etabonate Base (QID) | Loteprednol Etabonate Suspension (QID) |
|---|---|---|---|---|---|---|
| Age, Customized <=19 years | 2 participants | 8 participants | 3 participants | 1 participants | 1 participants | 1 participants |
| Age, Customized 20 - 64 years | 18 participants | 91 participants | 18 participants | 18 participants | 18 participants | 19 participants |
| Age, Customized >=65 years | 0 participants | 2 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 98 Participants | 19 Participants | 20 Participants | 20 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 60 Participants | 13 Participants | 13 Participants | 13 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 41 Participants | 8 Participants | 7 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 4 / 20 | 5 / 20 | 1 / 20 | 6 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Conjunctival Redness
Evaluated by investigator at 7, 15 and 20 minutes post challenge on a scale of 0-4 where 0= no redness and 4=extremely severe redness.
Time frame: Visit 4 (8 hr re-challenge)
Population: Visit 4, Re-challenge Conjunctival Hyperemia Scores, ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 7 min | 1.76 Units on a scale | Standard Deviation 0.62 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 20 min | 2.02 Units on a scale | Standard Deviation 0.72 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 15 min | 1.95 Units on a scale | Standard Deviation 0.66 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 15 min | 2.13 Units on a scale | Standard Deviation 0.829 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 7 min | 1.99 Units on a scale | Standard Deviation 0.709 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 20 min | 2.06 Units on a scale | Standard Deviation 0.811 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 15 min | 2.28 Units on a scale | Standard Deviation 0.766 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 7 min | 2.11 Units on a scale | Standard Deviation 0.649 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 20 min | 2.28 Units on a scale | Standard Deviation 0.691 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 7 min | 2.16 Units on a scale | Standard Deviation 0.619 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 20 min | 2.16 Units on a scale | Standard Deviation 0.585 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 15 min | 2.18 Units on a scale | Standard Deviation 0.6 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 15 min | 2.71 Units on a scale | Standard Deviation 0.597 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 7 min | 2.59 Units on a scale | Standard Deviation 0.501 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 20 min | 2.74 Units on a scale | Standard Deviation 0.592 |
Primary
Ocular Itching
Evaluated by subject at 3, 5, and 7 min post challenge on a scale of 0-4 where 0=no itching and 4=incapacitating itch.
Time frame: Visit 4 (8 hr re-challenge)
Population: Visit 4, Re-challenge Ocular Itching Scores - Primary Analysis ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Ocular Itching | 3 Min | 1.48 Units on a Scale | Standard Deviation 1.04 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 7 Min | 1.54 Units on a Scale | Standard Deviation 1.035 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 5 Min | 1.63 Units on a Scale | Standard Deviation 1.036 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 5 Min | 2.13 Units on a Scale | Standard Deviation 0.988 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 3 Min | 1.84 Units on a Scale | Standard Deviation 0.978 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 7 Min | 2.03 Units on a Scale | Standard Deviation 1.097 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 5 Min | 1.96 Units on a Scale | Standard Deviation 0.96 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 3 Min | 1.82 Units on a Scale | Standard Deviation 0.954 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 7 Min | 1.89 Units on a Scale | Standard Deviation 0.993 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 3 Min | 1.93 Units on a Scale | Standard Deviation 0.794 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 7 Min | 2.04 Units on a Scale | Standard Deviation 0.951 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 5 Min | 2.12 Units on a Scale | Standard Deviation 0.918 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 5 Min | 2.78 Units on a Scale | Standard Deviation 0.924 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 3 Min | 2.68 Units on a Scale | Standard Deviation 0.916 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 7 Min | 2.71 Units on a Scale | Standard Deviation 0.899 |
Secondary
Conjunctival Redness
Evaluated by investigator at 7, 15 and 20 minutes post challenge on a scale of 0-4 where 0= no redness and 4=extremely severe redness.
Time frame: Visit 3 (initial challenge)
Population: Visit 3 Conjunctival Hyperemia Scores - ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 7 min | 2.14 units on a scale | Standard Deviation 0.584 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 20 min | 2.31 units on a scale | Standard Deviation 0.541 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 15 min | 2.26 units on a scale | Standard Deviation 0.509 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 15 min | 2.20 units on a scale | Standard Deviation 0.737 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 7 min | 2.05 units on a scale | Standard Deviation 0.484 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 20 min | 2.24 units on a scale | Standard Deviation 0.631 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 15 min | 2.28 units on a scale | Standard Deviation 0.664 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 7 min | 2.22 units on a scale | Standard Deviation 0.593 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 20 min | 2.18 units on a scale | Standard Deviation 0.706 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 7 min | 2.25 units on a scale | Standard Deviation 0.486 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 20 min | 2.33 units on a scale | Standard Deviation 0.59 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 15 min | 2.43 units on a scale | Standard Deviation 0.415 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 15 min | 2.42 units on a scale | Standard Deviation 0.795 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 7 min | 2.41 units on a scale | Standard Deviation 0.663 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 20 min | 2.42 units on a scale | Standard Deviation 0.834 |
Secondary
Conjunctival Redness
Evaluated by investigator at 7, 15 and 20 minutes post challenge on a scale of 0-4 where 0= no redness and 4=extremely severe redness.
Time frame: Visit 4 (initial challenge)
Population: Visit 4 Conjunctival Hyperemia Scores - ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 7 min | 1.96 units on a scale | Standard Deviation 0.755 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 20 min | 2.15 units on a scale | Standard Deviation 0.777 |
| Loteprednol Etabonate Base (QD) | Conjunctival Redness | 15 min | 2.05 units on a scale | Standard Deviation 0.793 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 15 min | 2.19 units on a scale | Standard Deviation 0.777 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 7 min | 2.19 units on a scale | Standard Deviation 0.683 |
| Loteprednol Etabonate Base (BID) | Conjunctival Redness | 20 min | 2.16 units on a scale | Standard Deviation 0.828 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 15 min | 2.28 units on a scale | Standard Deviation 0.717 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 7 min | 2.26 units on a scale | Standard Deviation 0.661 |
| Loteprednol Etabonate Base (QID) | Conjunctival Redness | 20 min | 2.28 units on a scale | Standard Deviation 0.701 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 7 min | 2.22 units on a scale | Standard Deviation 0.353 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 20 min | 2.29 units on a scale | Standard Deviation 0.573 |
| Loteprednol Etabonate Suspension (QID) | Conjunctival Redness | 15 min | 2.36 units on a scale | Standard Deviation 0.459 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 15 min | 2.83 units on a scale | Standard Deviation 0.479 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 7 min | 2.70 units on a scale | Standard Deviation 0.445 |
| Vehicle of Loteprednol Etabonate | Conjunctival Redness | 20 min | 2.80 units on a scale | Standard Deviation 0.544 |
Secondary
Ocular Itching
Evaluated by the subject at 3, 5 and 7 min post-challenge on a scale of 0-4 where 0=no itching and 4=incapacitating itch.
Time frame: Visit 3 (initial challenge)
Population: Visit 3 Ocular Itching Scores - ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Ocular Itching | 5 min | 2.45 units on a scale | Standard Deviation 0.781 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 3 Min | 2.50 units on a scale | Standard Deviation 0.829 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 7 min | 2.38 units on a scale | Standard Deviation 0.872 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 7 min | 2.21 units on a scale | Standard Deviation 0.783 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 3 Min | 2.00 units on a scale | Standard Deviation 0.778 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 5 min | 2.15 units on a scale | Standard Deviation 0.745 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 3 Min | 2.31 units on a scale | Standard Deviation 0.889 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 5 min | 2.46 units on a scale | Standard Deviation 1.016 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 7 min | 2.21 units on a scale | Standard Deviation 1.044 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 5 min | 2.47 units on a scale | Standard Deviation 0.979 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 3 Min | 2.28 units on a scale | Standard Deviation 0.946 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 7 min | 2.38 units on a scale | Standard Deviation 1.062 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 3 Min | 2.50 units on a scale | Standard Deviation 1 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 7 min | 2.45 units on a scale | Standard Deviation 0.81 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 5 min | 2.63 units on a scale | Standard Deviation 0.863 |
Secondary
Ocular Itching
Evaluated by the subject at 3, 5 and 7 min post-challenge on a scale of 0-4 where 0=no itching and 4=incapacitating itch.
Time frame: Visit 4 (initial challenge)
Population: Visit 4 Ocular Itching Scores - ITT Population with LOCF included data from all randomized subjects who received treatment and had at least 1 post-CAC assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Loteprednol Etabonate Base (QD) | Ocular Itching | 3 Min | 2.02 units on a scale | Standard Deviation 0.978 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 7 min | 2.11 units on a scale | Standard Deviation 1.026 |
| Loteprednol Etabonate Base (QD) | Ocular Itching | 5 min | 2.19 units on a scale | Standard Deviation 1.04 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 5 min | 2.14 units on a scale | Standard Deviation 1.071 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 3 Min | 1.93 units on a scale | Standard Deviation 1.13 |
| Loteprednol Etabonate Base (BID) | Ocular Itching | 7 min | 2.11 units on a scale | Standard Deviation 0.985 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 5 min | 2.15 units on a scale | Standard Deviation 0.888 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 3 Min | 2.04 units on a scale | Standard Deviation 0.913 |
| Loteprednol Etabonate Base (QID) | Ocular Itching | 7 min | 2.13 units on a scale | Standard Deviation 0.917 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 3 Min | 2.17 units on a scale | Standard Deviation 0.846 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 7 min | 2.22 units on a scale | Standard Deviation 0.953 |
| Loteprednol Etabonate Suspension (QID) | Ocular Itching | 5 min | 2.32 units on a scale | Standard Deviation 0.853 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 5 min | 2.82 units on a scale | Standard Deviation 0.877 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 3 Min | 2.55 units on a scale | Standard Deviation 0.88 |
| Vehicle of Loteprednol Etabonate | Ocular Itching | 7 min | 2.71 units on a scale | Standard Deviation 0.875 |