Allergic Conjunctivitis
Conditions
Brief summary
The purpose of this study is to establish the safety and efficacy of ketotifen/naphazoline ophthalmic solution compared to vehicle and its individual components in alleviating the signs and symptoms of conjunctival allergen challenge (CAC)-induced allergic conjunctivitis.
Interventions
One drop of ketotifen fumarate 0.025% and naphazoline HCl 0.05% ophthalmic solution at visit 3 and visit 4.
DRUGNaphazoline
One drop of naphazoline HCl 0.05% ophthalmic solution at visits 3 and 4.
DRUGKetotifen
One drop of ketotifen fumarate 0.025% ophthalmic solution at visits 3 and 4.
DRUGVehicle
One drop of vehicle ophthalmic solution at visit 3 and visit 4.
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 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 0.7 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 for at least 2 out of 3 time points 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 | 3, 5, and 7 minutes post challenge at 14 days | Ocular itching was evaluated by the participant at 3, 5, and 7 minutes post challenge. Assessments were made using a 0-4 numerical analog scale, allowing 0.5-unit increments (but disallowing 0.25-unit increments), where: 0.0=None and 4.0=Incapacitating itch with an irresistible urge to rub |
| Conjunctival Redness | 7, 15, and 20 minutes post challenge at 14 days | Conjunctival hyperemia was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were completed using a 0-4 numerical analog scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ciliary Redness | 7, 15, and 20 minutes post challenge at 14 days | Ciliary hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using the same 0-4 scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe. |
| Episcleral Redness | 7, 15, and 20 minutes post challenge at 14 days | Episcleral hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using the same 0-4 scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe. |
| Chemosis | 7, 15, and 20 minutes post challenge at 14 days | Chemosis was evaluated by the Investigator at 7, 15, and 20 minutes post challenge on a 0-4 numerical analog scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe. |
| Eyelid Swelling | 7, 15, and 20 minutes post challenge at 14 days | Lid swelling was evaluated by the participant at 7, 15, and 20 minutes post challenge on a 0-3 numerical analog scale, with 0.5-unit increments disallowed, where: 0.0=None and 3.0=Severe. |
| Percentage of Eyes With hTearing | 7, 15, and 20 minutes post challenge at 14 days | Tearing was evaluated by the participant at 7, 15, and 20 minutes post challenge. Tearing was recorded as either absent or present. |
| Percentage of Eyes With Ocular Mucus Discharge | 7, 15, and 20 minutes post challenge at 14 days | Ocular mucous discharge was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Mucous discharged was recorded as either absent or present. |
Countries
United States
Participant flow
Recruitment details
There were 70 eyes in the KetoNaph group, 72 in the ketotifen group, 70 in the naphazoline group, and 70 in the vehicle group, for a total of 282 eyes (141 subjects).
Participants by arm
| Arm | Count |
|---|---|
| Ketotifen/Naphazoline Ketotifen/naphazoline ophthalmic solution administered in either the right eye, left eye or both eyes at visit 3 and visit 4.
Ketotifen/naphazoline: One drop of ketotifen fumarate 0.025% and naphazoline HCl 0.05% ophthalmic solution at visit 3 and visit 4. | 35 |
| Ketotifen Ketotifen ophthalmic solution administered in either the right eye, left eye or both eyes at visit 3 and visit 4.
Ketotifen: One drop of ketotifen fumarate 0.025% ophthalmic solution at visits 3 and 4. | 36 |
| Naphazoline Naphazoline ophthalmic solution administered in either the right eye, left eye or both eyes at visit 3 and visit 4.
Naphazoline: One drop of naphazoline HCl 0.05% ophthalmic solution at visits 3 and 4. | 35 |
| Vehicle Vehicle of ketotifen/naphazoline ophthalmic solution administered in either the right eye, left eye or both eyes at visit 3 and visit 4.
Vehicle: One drop of vehicle ophthalmic solution at visit 3 and visit 4. | 35 |
| Total | 141 |
Baseline characteristics
| Characteristic | Ketotifen/Naphazoline | Ketotifen | Naphazoline | Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.1 years | 40.7 years | 38.2 years | 38.4 years | 38.4 years |
| Sex: Female, Male Female | 16 Participants | 21 Participants | 18 Participants | 18 Participants | 73 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 17 Participants | 17 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 36 | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Conjunctival Redness
Conjunctival hyperemia was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were completed using a 0-4 numerical analog scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challeng assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Conjunctival Redness | 7 minutes post-challeng | 0.89 score on a scale | Standard Deviation 0.87 |
| Ketotifen/Naphazoline | Conjunctival Redness | 20 minutes post-challenge | 1.13 score on a scale | Standard Deviation 1.02 |
| Ketotifen/Naphazoline | Conjunctival Redness | 15 minutes post-challenge | 1.13 score on a scale | Standard Deviation 1 |
| Ketotifen | Conjunctival Redness | 7 minutes post-challeng | 1.49 score on a scale | Standard Deviation 0.83 |
| Ketotifen | Conjunctival Redness | 20 minutes post-challenge | 1.88 score on a scale | Standard Deviation 0.89 |
| Ketotifen | Conjunctival Redness | 15 minutes post-challenge | 1.80 score on a scale | Standard Deviation 0.87 |
| Naphazoline | Conjunctival Redness | 15 minutes post-challenge | 1.69 score on a scale | Standard Deviation 0.89 |
| Naphazoline | Conjunctival Redness | 7 minutes post-challeng | 1.63 score on a scale | Standard Deviation 0.84 |
| Naphazoline | Conjunctival Redness | 20 minutes post-challenge | 1.57 score on a scale | Standard Deviation 0.92 |
| Vehicle | Conjunctival Redness | 7 minutes post-challeng | 2.06 score on a scale | Standard Deviation 0.77 |
| Vehicle | Conjunctival Redness | 20 minutes post-challenge | 2.18 score on a scale | Standard Deviation 0.85 |
| Vehicle | Conjunctival Redness | 15 minutes post-challenge | 2.26 score on a scale | Standard Deviation 0.78 |
Primary
Ocular Itching
Ocular itching was evaluated by the participant at 3, 5, and 7 minutes post challenge. Assessments were made using a 0-4 numerical analog scale, allowing 0.5-unit increments (but disallowing 0.25-unit increments), where: 0.0=None and 4.0=Incapacitating itch with an irresistible urge to rub
Time frame: 3, 5, and 7 minutes post challenge at 14 days
Population: The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challeng assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Ocular Itching | 3 minutes post-challenge | 0.43 score on a scale | Standard Deviation 0.62 |
| Ketotifen/Naphazoline | Ocular Itching | 7 minutes post-challenge | 0.60 score on a scale | Standard Deviation 0.83 |
| Ketotifen/Naphazoline | Ocular Itching | 5 minutes post-challenge | 0.65 score on a scale | Standard Deviation 0.76 |
| Ketotifen | Ocular Itching | 3 minutes post-challenge | 0.40 score on a scale | Standard Deviation 0.65 |
| Ketotifen | Ocular Itching | 7 minutes post-challenge | 0.56 score on a scale | Standard Deviation 0.87 |
| Ketotifen | Ocular Itching | 5 minutes post-challenge | 0.59 score on a scale | Standard Deviation 0.79 |
| Naphazoline | Ocular Itching | 5 minutes post-challenge | 1.67 score on a scale | Standard Deviation 1.01 |
| Naphazoline | Ocular Itching | 3 minutes post-challenge | 1.60 score on a scale | Standard Deviation 0.92 |
| Naphazoline | Ocular Itching | 7 minutes post-challenge | 1.54 score on a scale | Standard Deviation 0.96 |
| Vehicle | Ocular Itching | 3 minutes post-challenge | 1.81 score on a scale | Standard Deviation 0.88 |
| Vehicle | Ocular Itching | 7 minutes post-challenge | 1.84 score on a scale | Standard Deviation 1.01 |
| Vehicle | Ocular Itching | 5 minutes post-challenge | 1.96 score on a scale | Standard Deviation 0.94 |
Secondary
Chemosis
Chemosis was evaluated by the Investigator at 7, 15, and 20 minutes post challenge on a 0-4 numerical analog scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Chemosis | 15 minutes post-challenge | 0.34 score on a scale | Standard Deviation 0.38 |
| Ketotifen/Naphazoline | Chemosis | 7 minutes post-challenge | 0.27 score on a scale | Standard Deviation 0.33 |
| Ketotifen/Naphazoline | Chemosis | 20 minutes post-challenge | 0.39 score on a scale | Standard Deviation 0.41 |
| Ketotifen | Chemosis | 15 minutes post-challenge | 0.46 score on a scale | Standard Deviation 0.47 |
| Ketotifen | Chemosis | 7 minutes post-challenge | 0.28 score on a scale | Standard Deviation 0.3 |
| Ketotifen | Chemosis | 20 minutes post-challenge | 0.49 score on a scale | Standard Deviation 0.46 |
| Naphazoline | Chemosis | 7 minutes post-challenge | 0.39 score on a scale | Standard Deviation 0.4 |
| Naphazoline | Chemosis | 20 minutes post-challenge | 0.54 score on a scale | Standard Deviation 0.58 |
| Naphazoline | Chemosis | 15 minutes post-challenge | 0.54 score on a scale | Standard Deviation 0.55 |
Secondary
Ciliary Redness
Ciliary hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using the same 0-4 scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Ciliary Redness | 15 minutes post-challenge | 1.05 score on a scale | Standard Deviation 1.05 |
| Ketotifen/Naphazoline | Ciliary Redness | 7 minutes post-challenge | 0.81 score on a scale | Standard Deviation 0.86 |
| Ketotifen/Naphazoline | Ciliary Redness | 20 minutes post-challenge | 1.04 score on a scale | Standard Deviation 1.03 |
| Ketotifen | Ciliary Redness | 15 minutes post-challenge | 1.76 score on a scale | Standard Deviation 0.91 |
| Ketotifen | Ciliary Redness | 7 minutes post-challenge | 1.33 score on a scale | Standard Deviation 0.88 |
| Ketotifen | Ciliary Redness | 20 minutes post-challenge | 1.76 score on a scale | Standard Deviation 0.94 |
| Naphazoline | Ciliary Redness | 7 minutes post-challenge | 1.49 score on a scale | Standard Deviation 0.89 |
| Naphazoline | Ciliary Redness | 20 minutes post-challenge | 1.54 score on a scale | Standard Deviation 0.92 |
| Naphazoline | Ciliary Redness | 15 minutes post-challenge | 1.59 score on a scale | Standard Deviation 0.91 |
Secondary
Episcleral Redness
Episcleral hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using the same 0-4 scale, allowing 0.5-unit increments, where: 0.0=None and 4.0=Extremely severe.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Episcleral Redness | 15 minutes post-challenge | 1.17 score on a scale | Standard Deviation 1.01 |
| Ketotifen/Naphazoline | Episcleral Redness | 7 minutes post-challenge | 0.91 score on a scale | Standard Deviation 0.89 |
| Ketotifen/Naphazoline | Episcleral Redness | 20 minutes post-challenge | 1.15 score on a scale | Standard Deviation 1.03 |
| Ketotifen | Episcleral Redness | 15 minutes post-challenge | 1.76 score on a scale | Standard Deviation 0.88 |
| Ketotifen | Episcleral Redness | 7 minutes post-challenge | 1.51 score on a scale | Standard Deviation 0.85 |
| Ketotifen | Episcleral Redness | 20 minutes post-challenge | 1.88 score on a scale | Standard Deviation 0.9 |
| Naphazoline | Episcleral Redness | 7 minutes post-challenge | 1.65 score on a scale | Standard Deviation 0.86 |
| Naphazoline | Episcleral Redness | 20 minutes post-challenge | 1.60 score on a scale | Standard Deviation 0.94 |
| Naphazoline | Episcleral Redness | 15 minutes post-challenge | 1.68 score on a scale | Standard Deviation 0.94 |
Secondary
Eyelid Swelling
Lid swelling was evaluated by the participant at 7, 15, and 20 minutes post challenge on a 0-3 numerical analog scale, with 0.5-unit increments disallowed, where: 0.0=None and 3.0=Severe.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketotifen/Naphazoline | Eyelid Swelling | 15 minutes post-challenge | 0.2 score on a scale | Standard Error 0.5 |
| Ketotifen/Naphazoline | Eyelid Swelling | 7 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Ketotifen/Naphazoline | Eyelid Swelling | 20 minutes post-challenge | 0.2 score on a scale | Standard Error 0.5 |
| Ketotifen | Eyelid Swelling | 15 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Ketotifen | Eyelid Swelling | 7 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Ketotifen | Eyelid Swelling | 20 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Naphazoline | Eyelid Swelling | 7 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Naphazoline | Eyelid Swelling | 20 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
| Naphazoline | Eyelid Swelling | 15 minutes post-challenge | 0.2 score on a scale | Standard Error 0.4 |
Secondary
Percentage of Eyes With hTearing
Tearing was evaluated by the participant at 7, 15, and 20 minutes post challenge. Tearing was recorded as either absent or present.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Ketotifen/Naphazoline | Percentage of Eyes With hTearing | 15 minutes post-challenge | 4 eyes |
| Ketotifen/Naphazoline | Percentage of Eyes With hTearing | 7 minutes post-challenge | 7 eyes |
| Ketotifen/Naphazoline | Percentage of Eyes With hTearing | 20 minutes post-challenge | 5 eyes |
| Ketotifen | Percentage of Eyes With hTearing | 15 minutes post-challenge | 9 eyes |
| Ketotifen | Percentage of Eyes With hTearing | 7 minutes post-challenge | 11 eyes |
| Ketotifen | Percentage of Eyes With hTearing | 20 minutes post-challenge | 6 eyes |
| Naphazoline | Percentage of Eyes With hTearing | 7 minutes post-challenge | 13 eyes |
| Naphazoline | Percentage of Eyes With hTearing | 20 minutes post-challenge | 11 eyes |
| Naphazoline | Percentage of Eyes With hTearing | 15 minutes post-challenge | 12 eyes |
Secondary
Percentage of Eyes With Ocular Mucus Discharge
Ocular mucous discharge was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Mucous discharged was recorded as either absent or present.
Time frame: 7, 15, and 20 minutes post challenge at 14 days
Population: This outcome measure was not assessed for the Vehicle group. The intent to treat population consisted of participants who were randomized, received investigational treatment, and had at least 1 post-challenge assessment.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Ketotifen/Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 15 minutes post-challenge | 0 eyes |
| Ketotifen/Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 7 minutes post-challenge | 0 eyes |
| Ketotifen/Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 20 minutes post-challenge | 0 eyes |
| Ketotifen | Percentage of Eyes With Ocular Mucus Discharge | 15 minutes post-challenge | 0 eyes |
| Ketotifen | Percentage of Eyes With Ocular Mucus Discharge | 7 minutes post-challenge | 0 eyes |
| Ketotifen | Percentage of Eyes With Ocular Mucus Discharge | 20 minutes post-challenge | 0 eyes |
| Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 7 minutes post-challenge | 0 eyes |
| Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 20 minutes post-challenge | 0 eyes |
| Naphazoline | Percentage of Eyes With Ocular Mucus Discharge | 15 minutes post-challenge | 0 eyes |