Transcript Slide 1

Ocular Comfort Assessment of Bepotastine Besilate Ophthalmic
Solution 1.5% in Multicenter Conjunctival Allergen Challenge
Clinical Trial
JA Gow1, TT Macejko2, EJ Meier2, JI Williams1, TR McNamara1 for the Bepotastine
Besilate Ophthalmic Solutions Clinical Study Group
1ISTA
Pharmaceuticals®, Inc., Irvine, CA; 2Eye Care Associates of Greater Cincinnati, Inc., Fairfield, OH;
3Eye Care Associates of Greater Cincinnati, Inc., Mason, OH
Financial support: ISTA Pharmaceuticals®, Inc., Irvine, CA, USA
Financial disclosures: JA Gow, ISTA Pharmaceuticals®, Inc., employee; TT Macejko, ISTA Pharmaceuticals®,
Inc., principal investigator; EJ Meier, ISTA Pharmaceuticals®, Inc., principal investigator; JI Williams, ISTA
Pharmaceuticals®, Inc., employee;. TR McNamara, ISTA Pharmaceuticals®, Inc., employee.
ABSTRACT
 Purpose: To quantitatively establish the ocular comfort of bepotastine
besilate ophthalmic solution 1.5%, a dual acting histamine H1 receptor
antagonist approved by the FDA, compared to placebo using the
Conjunctival Allergen Challenge (CAC) clinical model of allergic
conjunctivitis
ABSTRACT
 Methods: This was a multi-center (5 sites), double-masked,
randomized, placebo-controlled clinical trial using the CAC model.
Eligible subjects were assigned according to a computer-generated
randomization list to either bepotastine besilate ophthalmic solution
1.5% (n=44) or placebo (n=43). Ocular comfort examination of test
agent was subject-assessed during the 3 separate study visits,
immediately upon instillation into the conjunctival sac and at 5
minutes post-instillation using a 0-3 grading scale (0=comfortable or
discomfort absent; 3=severely uncomfortable or intolerable). A
difference in mean comfort grades ≥1.0 unit was considered
clinically significant. Comfort results were compared to the adverse
event profiles of test agents.
ABSTRACT
 Results: There were no clinically or statistically significant
differences in ocular comfort or tolerability between bepotastine
besilate ophthalmic solution 1.5% compared to placebo at any study
visit during the enrollment period. The mean comfort scores (all
eyes) for the bepotastine groups ranged from 0.05 to 0.14 units,
while the mean comfort score for the placebo group ranged from
0.03 to 0.14 units, a difference (active – placebo) not above the
clinical or statistical significance thresholds. Neither treatmentemergent serious adverse events nor severe adverse events were
reported for bepotastine besilate ophthalmic solution 1.5%, and
follow-up visits were not needed for any enrolled subjects.
ABSTRACT
 Conclusion: Based upon the ocular comfort scale results, bepotastine
besilate ophthalmic solution 1.5% is comfortable after ophthalmic
dosing when assessed during a CAC efficacy clinical trial. The multicenter clinical results, combined with minimal adverse events,
demonstrate a favorable safety profile for bepotastine besilate
ophthalmic solution 1.5%.
CAC TRIAL PROCEDURES
•
Visit 1 and Visit 2:: Allergen Titration; Screening and Confirmation CAC Tests
Screening and confirmation CAC tests performed with allergen titration to induce bilateral ocular itching and
conjunctival redness grades ≥2 using a standardized 0-4 scale
•
•
BID Duration of Action CAC Test Visit: 16 Hours Post-Instillation
of Investigational Product
One drop of bepotastine besilate ophthalmic solution 1.5% or placebo OU
CAC OU of the challenge allergen subsequently was performed on each subject 15 minutes after test article
instillation,
and efficacy parameters as well as ocular comfort were quantitatively graded
•
•
BID Duration of Action CAC Test Visit: 8 Hours Post-Instillation
of Investigational Product
One drop of bepotastine besilate ophthalmic solution 1.5% or placebo OU
CAC OU of the challenge allergen subsequently was performed on each subject 15 minutes after test article
instillation,
and efficacy parameters as well as ocular comfort were quantitatively graded
•
•
Onset of Action CAC Test Visit: 15 Minutes Post-Instillation
of Investigational Product
One drop of bepotastine besilate ophthalmic solution 1.5% or placebo OU
CAC OU of the challenge allergen subsequently was performed on each subject 15 minutes after test article
instillation,
and efficacy parameters as well as ocular comfort were quantitatively graded
Figure 1. Algorithm of the CAC clinical trial procedures.
Ocular Comfort Grading Scale
0 Comfortable; discomfort absent
●
1 Generally comfortable; mild discomfort
Some
discomfort,
2
moderate comfort
but
tolerable;
3 Severely uncomfortable or intolerable
EFFICACY RESULTS
0.5
3
0.45
= Maximum Discomfort
Mean Comfort Grade
0.4
Mean Comfort Grade
2.5
2
0.35
0.3
0.25
[Enlargement of Graph]
0.2
0.15
0.1
0.05
1.5
0
1
Clinically Significant
Evidence of Discomfort
0.5
0
Onset of Action 8 Hr Duration
CAC
of Action CAC
16 Hr Duration
of Action CAC
Placebo Treatment Group
Onset of Action 8 Hr Duration
CAC
of Action CAC
16 Hr Duration
of Action CAC
Bepotastine Besilate Ophthalmic
Solution 1.5% Treatment Group
Figure 2. Comfort immediately upon instillation of test article
= Left Eye
= Right Eye
EFFICACY RESULTS
0.5
0.45
3
Mean Comfort Grade
0.4
Mean Comfort Grade
2.5
2
0.35
0.3
[Enlargement of Graph]
0.25
0.2
0.15
0.1
0.05
1.5
0
Clinically Significant
Evidence of Discomfort
1
0.5
0
Onset of Action 8 Hr Duration
CAC
of Action CAC
16 Hr Duration
of Action CAC
Placebo Treatment Group
Onset of Action 8 Hr Duration
CAC
of Action CAC
16 Hr Duration
of Action CAC
Bepotastine Besilate Ophthalmic
Solution 1.5% Treatment Group
= Left Eye
= Right Eye
Figure 3. Comfort 5 minutes after instillation of test article
ADVERSE EVENTS
Table 1. Number of Subjects Reporting Adverse Events Considered Possibly, Probably, or Definitely Related to
Treatment, by Category
Number of Subjects Reporting Adverse Event
Related to Treatment
Adverse Event
(All Mild or Moderate)
Placebo Treatment Group
Bepotastine Besilate 1.5%
Treatment Group
Eye Irritation
1
2
Eye Pain
1
0
Taste Related Issue
0
2
• There were no serious or severe adverse events in this study
• No subjects were discontinued from the study due to an adverse event
• All adverse events were rated as mild or moderate
• No follow-up visits were needed for any enrolled subject
CONCLUSIONS
 The mean comfort scores assessed by enrolled subjects were
very similar in both treatment groups
 The comfort of bepotastine besilate ophthalmic solution 1.5%
eyedrops was not different from placebo eye drops as judged by
clinical or statistical significance (P > 0.05 in all comparisons)
 There was neither immediate nor delayed discomfort noted with
instillation of either placebo eye drops or bepotastine besilate
ophthalmic solution 1.5% eye drops
 There was a generally high correlation in mean comfort scores for
both eyes of all subjects
 BEPREVE™ (bepotastine besilate ophthalmic solution) 1.5% was
approved by the FDA in September 2009 for the treatment of
ocular itching associated with the signs and symptoms of allergic
conjunctivitis
Reference: Gow, JA, Macejko TT, Meier EJ, Williams JI, McNamara TR for the Bepotastine Besilate Ophthalmic Solutions Clinical Study
Group. Ocular comfort assessment of bepotastine besilate ophthalmic solution 1.5% in multicenter conjunctival allergen challenge clinical trial.
Poster presented at: 36th Symposium on Cataract, IOL, and Refractive Surgery of the American Society of Cataract and Refractive Surgery;
April 9-14, 2010; Boston, MA. Abstract 737924.