Efficacy and Safety of AL-4943A Ophthalmic Solution in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

A Multi-Center, Randomized, Double-Masked, Vehicle and Active Controlled, Parallel-Group Efficacy and Safety Study of AL-4943A Ophthalmic Solution, 0.77% in Patients With Allergic Conjunctivitis Using the Conjunctival Allergen Challenge (CAC) Model

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01479374

Enrollment

397

Registered

2011-11-24

Start date

2012-01-31

Completion date

2012-03-31

Last updated

2013-06-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Allergic Conjunctivitis

Keywords

Allergic Conjunctivitis, Ocular Allergy

Brief summary

The purpose of this study was to assess the safety and efficacy of AL-4943A ophthalmic solution for the treatment of ocular itching associated with allergic conjunctivitis using the Conjunctival Allergen Challenge (CAC) model.

Detailed description

This study consisted of 5 Visits. Eligible patients underwent allergy testing using the Conjunctival Allergen Challenge (CAC) model, which reproduces the signs and symptoms of Seasonal Allergic Conjunctivitis by replicating the natural disease process. Patients demonstrating a positive reaction to the CAC at Visit 1 (screening) and Visit 2 (confirmatory) were randomized to treatment at Visit 3 (Day 0). The test article was instilled at Visit 3, with treatment efficacy CAC performed at 24 hours duration of action. The test article was instilled again at Visit 4 (Day 14), with treatment efficacy CAC performed at 16 hours duration of action. The test article was instilled a final time at Visit 5 (Day 21), with treatment efficacy performed at onset of action.

Interventions

DRUGAL-4943A ophthalmic solution

DRUGAL-4943A vehicle

Inactive ingredients used as placebo

DRUGOlopatadine hydrochloride ophthalmic solution, 0.2%

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Able to be dosed in both eyes, able and willing to make the required study visits and to follow instructions. * Diagnostic skin test indicative of allergy for cat hair, cat dander, grasses, ragweed, dust mite, dog dander, cockroach and/or trees within 24 months of Visit 1. * History of seasonal or perennial allergic conjunctivitis for at least 1 year prior to Visit 1. * Positive bilateral CAC response at Visit 1 and Visit 2. * Willing to discontinue contact lens wear for at least 72 hours prior to Visit 1 and throughout the study. * Other protocol-defined inclusion criteria may apply.

Exclusion criteria

* Known history or presence of persistent dry eye syndrome, or currently requiring frequent use (\> 4 days per week) of artificial tears, gels or lubricants, presence of punctal plugs, use of Restasis®, or topical ocular corticosteroids for dryness of eyes. * Presence of active blepharitis, active meibomian gland dysfunction, active rosacea affecting the ocular adnexa, follicular conjunctivitis, iritis, preauricular lymphadenopathy, ocular irritation not due to ocular allergy, or any other clinically significant ophthalmic abnormality that may affect the study outcomes. * Presumed or actual ocular infection (bacterial, viral or fungal) or history of ocular herpes in either eye as determined by patient history and/or examination within 30 days of Visit 1. * Presence of any chronic ocular degenerative condition or active intra-ocular inflammation in either eye that in the opinion of the Investigator is likely to advance/worsen during the time course of the study. * Any contraindications or hypersensitivities to the use of the study medication or their components. * Other protocol-defined

Design outcomes

Primary

Measure	Time frame	Description
Mean Ocular Itching at Onset of Action	3, 5, and 7 minute timepoints, post-CAC on Day 21 of receiving treatment	A treatment efficacy CAC was performed 27 minutes after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed.
Mean Ocular Itching at 16 Hours Duration of Action	3, 5, and 7 minute timepoints, post-CAC on Day 14 of receiving treatment	A treatment efficacy CAC was performed 16 hours after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed.

Secondary

Measure	Time frame	Description
Mean Total Redness at 24 Hours Duration of Action	7, 15, and 20 minute timepoints, post-CAC on Day 1 of receiving treatment	A treatment efficacy CAC was performed 24 hours after drop instillation. Total redness (0-12) is defined as the sum of ciliary redness (0-4 scale, from 0=none to 4=extremely severe), conjunctival redness (0-4 scale, from 0=none to 4=extremely severe), and episcleral redness (0-4 scale, from 0=none to 4=extremely severe). Average of total redness score over both eyes was analyzed.
Mean Conjunctival Redness at Onset of Action	7, 15, and 20 minute timepoints, post-CAC on Day 21 of receiving treatment	A treatment efficacy CAC was performed 27 minutes after drop instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed.
Mean Conjunctival Redness at 24 Hours Duration of Action	7, 15, and 20 minute timepoints, post-CAC on Day 1 of receiving treatment	A treatment efficacy CAC was performed 24 hours after drop instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed.
Mean Ocular Itching at 24 Hours Duration of Action	3, 5, and 7 minute timepoints, post-CAC on Day 1 of receiving treatment	A treatment efficacy CAC was performed 24 hours after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed.
Mean Conjunctival Redness at 16 Hours Duration of Action	7, 15, and 20 minute timepoints, post-CAC on Day 14 of receiving treatment	A treatment efficacy CAC was performed 16 hours after drop instillation. Conjunctival redness was assessed by the investigator on a 0-4 scale (0=none to 4=extremely severe). Average of conjunctival redness score over both eyes was analyzed.

Participant flow

Recruitment details

Patients were recruited from three US study centers.

Pre-assignment details

Of the 397 enrolled, 195 subjects did not qualify for treatment and were exited without exposure to product. Participant flow and baseline characteristics are presented for the 202 subjects qualifying for treatment and randomized 1:1:1 to receive AL-4943A, Vehicle, or Pataday.

Participants by arm

Arm	Count
AL-4943A AL-4943A ophthalmic solution, 1 drop to each eye, 3 nonconsecutive days	66
Vehicle AL-4943A vehicle, 1 drop to each eye, 3 nonconsecutive days	68
Pataday Olopatadine hydrochloride ophthalmic solution, 0.2%, 1 drop to each eye, 3 nonconsecutive days	68
Total	202

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	2	1	0
Overall Study	Decision Unrelated to Adverse Event	0	1	0
Overall Study	Lost to Follow-up	1	2	0
Overall Study	Other	0	4	5

Baseline characteristics

Characteristic	AL-4943A	Vehicle	Pataday	Total
Age, Customized 18 to 64 years	64 participants	66 participants	66 participants	196 participants
Age, Customized >=65 years	2 participants	2 participants	2 participants	6 participants
Region of Enrollment United States	66 participants	68 participants	68 participants	202 participants
Sex: Female, Male Female	43 Participants	39 Participants	42 Participants	124 Participants
Sex: Female, Male Male	23 Participants	29 Participants	26 Participants	78 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	0 / 66	0 / 68	0 / 68
serious Total, serious adverse events	0 / 66	0 / 68	0 / 68

Outcome results

Primary

Mean Ocular Itching at 16 Hours Duration of Action

A treatment efficacy CAC was performed 16 hours after drop instillation. Ocular itching was assessed by the patient on a 0-4 scale (0=none to 4=incapacitating itch). Average of ocular itching score over both eyes was analyzed.

Time frame: 3, 5, and 7 minute timepoints, post-CAC on Day 14 of receiving treatment