Ketotifen/Naphazoline Ophthalmic Solution in the Conjunctival Allergen Challenge Model of Allergic Conjunctivitis.

• Sponsor: Bausch & Lomb Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00769886
• Collaborator: (none)
• Enrollment: 144
• Location: 1
• Arms: 4
• Duration (Months): 8
• Patients Per Site Per Month: 18

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Conjunctivitis	Drug: Ketotifen/naphazoline; Drug: Ketotifen; Drug: Naphazoline; Drug: Vehicle	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Double-Masked, Randomized, Vehicle and Active Controlled Evaluation of the Onset and Duration of Action of KetoNaph Ophthalmic Solution in the Conjunctival Allergen Challenge Model of Acute Allergic Conjunctivitis
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KetoNaph KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution	Drug: Ketotifen/naphazoline; One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.
Active Comparator: Naphazoline Naphazoline HCl 0.05% ophthalmic solution	Drug: Naphazoline; One drop of naphazoline in study eye at vist 3 and visit 4.
Active Comparator: Ketotifen Ketotifen fumarate 0.025% ophthalmic solution	Drug: Ketotifen; One drop of Ketotifen in study eye at visit 3 and visit 4.
Placebo Comparator: Vehicle Vehicle of KetoNaph ophthalmic solution	Drug: Vehicle; One drop of vehicle in study eye at visit 3 and visit 4.

Outcome Measures

Primary Outcome Measures

1. 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.

2. Conjunctival Hyperemia [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 Outcome Measures

1. 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 a 0-4 scale, allowing 0.5- unit increments, with 0.0 = None and 4.0 = Extremely severe.

2. 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 a 0-4 scale, allowing 0.5- unit increments, with 0.0 = None and 4.0 = Extremely severe.

3. 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.

4. Eyelid Swelling [7, 15, and 20 minutes post challenge at 14 days]

   Lid swelling was evaluated by the subject 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.

5. Percentage of Eyes With Tearing [7, 15, and 20 minutes post challenge at 14 days]

   Tearing was evaluated by the subject at 7, 15, and 20 minutes post challenge (absent or present). Tearing was recorded as either absent or present.

6. Percentage of Eyes With Ocular Mucus Drainage [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 in 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ophthalmic Research Consultants, Inc.	North Andover	Massachusetts	United States	01845

Sponsors and Collaborators

• Bausch & Lomb Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch & Lomb Incorporated
• ClinicalTrials.gov Identifier: NCT00769886
• Other Study ID Numbers: 571
• First Posted: Oct 9, 2008
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Conjunctivitis; Conjunctivitis, Allergic; Ketotifen; Naphazoline

Study Results

Participant Flow

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Period Title: Overall Study
STARTED	36	36	35	37
COMPLETED	31	32	34	35
NOT COMPLETED	5	4	1	2

Baseline Characteristics

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle	Total
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.	Total of all reporting groups
Overall Participants	36	36	35	37	144
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	33.63	34.15	35.56	33.09	34.10
Sex: Female, Male (Count of Participants)
Female	20 55.6%	18 50%	18 51.4%	21 56.8%	77 53.5%
Male	16 44.4%	18 50%	17 48.6%	16 43.2%	67 46.5%

Outcome Measures

1. Primary Outcome

Title	Ocular Itching
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	37
Measure eyes	72	71	70	74
3 minutes post-challenge	0.50 (0.835)	0.49 (0.860)	1.87 (0.932)	1.93 (0.998)
5 minutes post-challenge	0.56 (0.785)	0.69 (0.923)	1.90 (0.936)	2.17 (0.885)
7 minutes post-challenge	0.56 (0.856)	0.72 (0.885)	1.75 (0.971)	1.97 (0.984)

2. Primary Outcome

Title	Conjunctival Hyperemia
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	37
Measure eyes	72	71	70	74
7 minutes post-challenge	1.13 (0.872)	1.49 (0.761)	1.62 (0.860)	2.24 (0.581)
15 minutes post-challenge	1.39 (0.865)	1.89 (0.712)	1.68 (0.957)	2.33 (0.551)
20 minutes post-challenge	1.26 (0.818)	1.77 (0.805)	1.53 (0.959)	2.24 (0.587)

3. Secondary Outcome

Title	Ciliary Redness
Description	Ciliary hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using a 0-4 scale, allowing 0.5- unit increments, with 0.0 = None and 4.0 = Extremely severe.
Time Frame	7, 15, and 20 minutes post challenge at 14 days

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	1.05 (0.873)	1.39 (0.774)	1.66 (0.917)
15 minutes post-challenge	1.28 (0.907)	1.79 (0.791)	1.71 (0.995)
20 minutes post-challenge	1.15 (0.854)	1.77 (0.810)	1.58 (1.032)

4. Secondary Outcome

Title	Episcleral Redness
Description	Episcleral hyperemia (redness) was evaluated by the Investigator at 7, 15, and 20 minutes post challenge. Assessments were made using a 0-4 scale, allowing 0.5- unit increments, with 0.0 = None and 4.0 = Extremely severe.
Time Frame	7, 15, and 20 minutes post challenge at 14 days

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	1.21 (0.891)	1.52 (0.749)	1.71 (0.951)
15 minutes post-challenge	1.41 (0.865)	1.87 (0.732)	1.77 (0.988)
20 minutes post-challenge	1.35 (0.895)	1.88 (0.777)	1.68 (1.026)

5. Secondary Outcome

Title	Chemosis
Description	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

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	0.22 (0.410)	0.22 (0.313)	0.51 (0.705)
15 minutes post-challenge	0.29 (0.488)	0.42 (0.420)	0.66 (0.787)
20 minutes post-challenge	0.34 (0.549)	0.41 (0.450)	0.66 (0.869)

6. Secondary Outcome

Title	Eyelid Swelling
Description	Lid swelling was evaluated by the subject 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

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	0.13 (0.373)	0.32 (0.604)	0.61 (0.783)
15 minutes post-challenge	0.25 (0.550)	0.37 (0.638)	0.61 (0.746)
20 minutes post-challenge	0.26 (0.581)	0.39 (0.686)	0.59 (0.729)

7. Secondary Outcome

Title	Percentage of Eyes With Tearing
Description	Tearing was evaluated by the subject at 7, 15, and 20 minutes post challenge (absent or present). Tearing was recorded as either absent or present.
Time Frame	7, 15, and 20 minutes post challenge at 14 days

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	3	11	23
15 minutes post-challenge	6	7	16
20 minutes post-challenge	5	7	13

8. Secondary Outcome

Title	Percentage of Eyes With Ocular Mucus Drainage
Description	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

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed for the Vehicle group.

Arm/Group Title	KetoNaph	Ketotifen	Naphazoline	Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.	Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.	Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.	Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
Measure Participants	36	36	35	0
Measure eyes	72	71	70	0
7 minutes post-challenge	7	12	13
15 minutes post-challenge	11	19	18
20 minutes post-challenge	10	16	18

Adverse Events

Time Frame	14 days
Arm/Group Title	KetoNaph		Ketotifen		Naphazoline		Vehicle
Arm/Group Description	KetoNaph (ketotifen fumarate 0.025%, naphazoline HCl 0.05%) ophthalmic solution Ketotifen/naphazoline: One drop of ketotifen/naphazoline in study eye at visit 3 and visit 4.		Ketotifen fumarate 0.025% ophthalmic solution Ketotifen: One drop of Ketotifen in study eye at visit 3 and visit 4.		Naphazoline HCl 0.05% ophthalmic solution Naphazoline: One drop of naphazoline in study eye at vist 3 and visit 4.		Vehicle of KetoNaph ophthalmic solution Vehicle: One drop of vehicle in study eye at visit 3 and visit 4.
All Cause Mortality
	KetoNaph		Ketotifen		Naphazoline		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	KetoNaph		Ketotifen		Naphazoline		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)		0/35 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	KetoNaph		Ketotifen		Naphazoline		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)		0/35 (0%)		0/37 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Contact sponsor directly for details.