AZARGA®

Find Comfort
in Strength
Presented by: Reham Fathy
Pharma Product Manager
 AZARGA ®
eye drops, suspension
• Fixed combination of Brinzolamide1%/Timolol
0.5%.
Therapeutic Indications:
• Decrease intraocular pressure (IOP) in
adult patients with open-angle glaucoma or
ocular hypertension for whom mono-therapy
provides insufficient IOP reduction.
 AZARGA ®
eye drops, suspension
Method of Administration:
• Use in adults, including the Elderly
– The dose is one drop of AZARGA® in the conjunctival
sac of the affected eye(s) twice daily.
• Pediatric Patients
– AZARGA® eye drops, suspension is not recommended for
use in children below 18 years due to a lack of data
on safety and efficacy
 AZARGA ®
eye drops, suspension
Summary of the Safety Profile:
• In two clinical trials of 6 and 12 months
duration involving 394 patients treated
with AZARGA® eye drops, suspension, the
most frequently reported adverse reaction
was transient blurred vision upon
instillation (3.6%), lasting from a few
seconds to a few minutes.
 AZARGA ®
eye drops, suspension
Contraindications:
• Hypersensitivity to the active substances, or to any
of the excepients.
• Bronchial asthma, a history of bronchial asthma, or
severe chronic obstructive pulmonary disease.
• Sinus bradycardia, second or third degree
atrioventricular block, overt cardiac failure, or
cardiogenic shock.
• Severe allergic rhinitis and bronchial hyper-
reactivity;
• Hyperchloraemic acidosis
• Patients with severe renal impairment.
AZARGA® Suspension Efficacy
Studies
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination
OBJECTIVE:
12-Month Study
To compare the efficacy and safety of brinzolamide 1%/timolol 0.5% vs. dorzolamide
2%/timolol 0.5%
DESIGN: Randomized, double-masked, parallel group, multi-center
STUDY POPULATION:Patients with open-angle glaucoma or ocular hypertension
BASELINE : IOP 8AM ≥ 24 mmHg, 10AM & 4PM ≥ 21 mmHg
TREATMENT ARMS

• AZARGA® Suspension BID (n=220)

• dorzolamide/timolol fixed combination* BID (n=217)
VISITS: Screening, Week 2, Month 3, 6, 9 and 12
IOP Measurements at: 8AM, 10AM, 4PM†
* Trademark is the property of its owner.
† An additional IOP measurement was obtained at month 6 and month 12 visits
Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle
glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination
12-Month Study

* Trademark is the property of its owner.

Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-
angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination
12-Month Study

Dorzolamide/timolol (n=201)

Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-
angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination
12-Month Study

Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-
angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination
12-Month Study Summary
• AZARGA® Suspension lowered IOP from 7.2 to 9.1 mmHg (28% to
35% reduction from baseline), clinically equivalent to
drozolamide/timolol fixed combination.
• The most common adverse event within this 12-month study for
AZARGA® Suspension was blurring (3.6%), while drozolamide/timolol
fixed combination. had eye irritation (10.6%) and pain (6.5%).
Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-
angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
AZARGA® Suspension
Comfort/Patient Preference
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study
OBJECTIVE:To evaluate the ocular discomfort, based on burning and stinging, of
brinzolamide 1%/timolol 0.5% compared to dorzolamide 2%/timolol 0.5%
DESIGN: Prospective, double-masked, parallel-group, randomized, multi-center
TREATMENT ARMS:

• AZARGA® Suspension BID (n=48 patients)

• dorzolamide/tiomol fixed combination BID (n=48 patients)
VISITS: Screening, Week 1
DISCOMFORT SCALE:Discomfort Score: Week 1 visit in 7±1 days at 8AM (±60 minutes)
0=None, 1=Mild, 2=Moderate, 3=Severe and 4=Very Severe
Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study
Dorzolamide/timolol (n=48)

Randomized to
either AZARGA
or for BID
dosing for 7
days
Dorzolamide/ti
molol

* Trademark is the property of its owner.

Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study

Dorzolamide/timolol
(n=47)

Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study

Dorzolamide/t
imolol (n=7)

Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study

Dorzolamide/timolol
Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Comfort Study
Summary
• AZARGA Suspension is significantly
® more comfortable than
dorzolamide/ timolol fixed combination*.
• A significantly higher percentage of patients (49%) using AZARGA®
Suspension experienced no ocular burning or stinging compared to
patients on dorzolamide/ timolol fixed combination* (15%) (p=0.0004).

* Trademark is the property of its owner.

Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to
BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Preference Study
OBJECTIVE: To determine patient preference of brinzolamide 1%/timolol 0.5% compared to
dorzolamide 2%/timolol 0.5%
DESIGN: Prospective, double-masked, randomized, multi-center crossover study
TREATMENT ARMS :
1- AZARGA® Suspension, then dorzolamide/timolol fixed combination * (n=63 patients)
2- dorzolamide/timolol fixed combination then AZARGA® Suspension (n=66 patients)

Mundorf TK, Rauchman SH, Williams RD, et al. A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs Cosopt (dorzolamide/timolol fixed
combination) in patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2008;2:623-628.

* Trademark is the property of its owner.

 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Preference Study
VISITS: Screening, Day 1, Day 2

Discomfort Score collected on Day 1, Day 2

DISCOMFORT SCALE 0=No discomfort to 9=Substantial discomfort

Preference Question collected on Day 2

POSSIBLE RESPONSES: Prefer 1st medication, No preference, Prefer 2nd medication

 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Preference Study

Dorzolamide/timolol (n=22)

Mundorf TK, Rauchman SH, Williams RD, et al. A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs (dorzolamide/timolol fixed combination) in
patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2008;2:623-628.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Preference Study

Dorzolamide/timolol (n=22)
* Trademark is the property of its owner. Discomfort scale 0-9

Mundorf TK, Rauchman SH, Williams RD, et al. A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs (dorzolamide/timolol fixed combination) in
patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2008;2:623-628.
 AZARGA® Suspension vs.
dorzolamide/timolol fixed
combination Preference Study
Summary
• , AZARGA Suspension was preferred by 79% of patients.
®

• Mean discomfort scores for dorzolamide/timolol fixed combination *

were more than double those for AZARGA® Suspension.
• AZARGA® Suspension was significantly more comfortable than
dorzolamide/timolol fixed combination *.

* Trademark is the property of its owner.

Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to BID-dosed
dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
Relevance of Comfort
 Why is AZARGA® Suspension
More Comfortable?

Dorzolamide/timolol

• The pH of AZARGA® Suspension is 7.2 which is similar to

that of human tears 2-4

• The pH of dorzolamide/timolol fixed combination is 5.65 5

1. Garcia-Valldecabres M, Lopez-Alemany A, Refojo MF. pH Stability of ophthalmic solutions. Optometry 2004;75:161-8.
2. AZARGA® Suspension Summary of Product Characteristics.
3. Yamada M, Mochizuki H, Kawai M, et al. Fluorophotometric measurement of pH of human tears in vivo. Curr Eye Res. 1997;16:482-486.
4. Maurice D. The Charles Prentice Award lecture 1989: the physiology of tears. Optom Vis Sci. 1990;67:391-399.
5. Dorzolamide/timolol fixed combination drug description. Electronic Medicines Compendium Website. http://emc.medicines.org.uk/. Accessed May 22, 2008.
 Why is Comfort Important?

Greater comfort can have

a positive effect on patient adherence to IOP-lowering
medication regimens.1,2

1. Chan K, Testa M, McCluskey P. Ocular comfort of combination glaucoma therapies: brimonidine 0.2%/timolol 0.5% compared to dorzolamide 2%/timolol 0.5%.
J Ocul Pharmacol Ther. 2007;23:372-376.
2. Tsai JC, McClure CA, Ramos SE, et al. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393-8.
AZARGA® Suspension Clinical Study
Summary
• AZARGA® Suspension lowered IOP by as much as 9.1 mmHg
(35% reduction from baseline)
• AZARGA® Suspension produced clinically meaningful IOP reductions
from baseline which were similar to dorzolamide/timolol fixed combination
• AZARGA® Suspension is significantly more comfortable than dorzolamide/timolol fixed
combination
• Greater comfort can have a positive effect on patient adherence to
IOP-lowering medications
 AZARGA® Suspension Clinical
Study Summary – Comfort
• A significantly higher percentage (49%), on AZARGA® Suspension experienced no
burning or stinging compared to patients on dorzolamide/timolol fixed combination
(15%) (p=0.0004)1.
• Of those patients (n=106) expressing a preference, AZARGA® Suspension was
preferred by 79% of patients, while only 21% of patients preferred
dorzolamide/timolol fixed combination.
• In a 12-month study, 10.6% of dorzolamide/timolol fixed combination patients
experienced eye irritation versus 2.7% of AZARGA® patients (p=0.0009)3.
• Greater comfort can have a positive effect on patient adherence to
IOP-lowering medications

1. Vold SD, Evans RM, Stewart RH, et al. A one-week comfort study of BID-dosed brinzolamide 1%/timolol 0.5% ophthalmic suspension fixed combination compared to BID-
dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008;24:601-605.
2. Mundorf TK, Rauchman SH, Williams RD, et al. A patient preference comparison of Azarga (brinzolamide/timolol fixed combination) vs Cosopt (dorzolamide/timolol fixed
combination) in patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2008;2:623-628.
3. Manni G, Denis P, Chew P, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-
angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293-300.
4. Chan K, Testa M, McCluskey P. Ocular comfort of combination glaucoma therapies: brimonidine 0.2%/timolol 0.5% compared to dorzolamide 2%/timolol 0.5%.
J Ocul Pharmacol Ther. 2007;23:372-376.
5. Tsai JC, McClure CA, Ramos SE, et al. Compliance barriers in glaucoma: a systematic classification. J Glaucoma. 2003;12:393-8.
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