Maximum Medical Therapy: Brinzolamide/Brimonidine And Travoprost/Timolol Fixed-Dose Combinations In Glaucoma And Ocular Hypertension

Figures & data

Figure 1 Study design. *One drop instilled at 09:00±30 min and 21:00±30 min. ^#One drop instilled at 09:00±30 min or 21:00±30 min. For the evening dose, patients waited for 15 min after instillation of TTFC, and then instilled the masked drug. **Study TTFC was administered at 21:00±30 min if the patient was dosed with TTFC in the evenings prior to Screening, or at 09:00±30 min on the following day if the patient was dosed with TTFC in the mornings prior to Screening.

Abbreviations: BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; BID, twice daily, E1, eligibility visit 1, E2, eligibility visit 2; QD, once daily; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination.

Table 1 Demographics And Baseline Characteristics (Full Analysis Set)

Characteristics	BBFC+TTFC N=67	Vehicle+TTFC N=67
Age, years (mean [SD])	65.7 (13.47)	65.7 (11.77)
Gender, female, n (%)	32 (47.8)	41 (61.2)
Race, n (%)
Caucasian	50 (74.6)	57 (85.1)
Black or African American	2 (3.0)	0 (0.0)
Asian	6 (9.0)	7 (10.4)
Others	9 (13.4)	3 (4.5)
Ethnicity, n (%)
Hispanic or Latino	29 (43.3)	26 (38.8)
Not Hispanic or Latino	38 (56.7)	41 (61.2)
Region, n (%)
EMEA	35 (52.2)	39 (58.2)
Asia	6 (9.0)	8 (11.9)
LACAR	26 (38.8)	20 (29.9)
BL IOP (mean [SD], mmHg)	21.6 (1.78)	21.8 (1.90)
BL IOP category, n (%)
<19 mmHg	0 (0.0)	2 (3.0)
19–24 mmHg	64 (95.5)	60 (89.6)
24–28 mmHg	3 (4.5)	5 (7.5)
Corneal thickness (mean [SD], μm)	538.0 (34.14)	540.0 (35.22)
Diagnosis, n (%)
OHT	12 (17.9)	12 (17.9)
Primary OAG	54 (80.6)	47 (70.1)
Pseudoexfoliation OAG	0 (0.0)	7 (10.4)
Pigment Dispersion OAG	1 (1.5)	1 (1.5)

Note: BL IOP defined as the average of 09:00 and 11:00 values.

Abbreviations: BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; BL, baseline; Countries included from EMEA region: Belgium, Germany, Greece, Italy, Poland, Spain, UK; Countries included from Asia: S. Korea, Malaysia, Taiwan, Australia; FAS, full analysis set; IOP, intraocular pressure; LACAR: Argentina, Chile, Colombia; N, total number of patients; n, number of patients; OAG, open-angle glaucoma; OHT, ocular hypertension; SD, standard deviation; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination.

Figure 2 Patient disposition.

Abbreviations: AE, adverse event; BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; N, total number of patients; n, number of patients; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination.

Figure 3 Mean change in diurnal intraocular pressure from baseline at Week 6 (Full analysis set). *BL IOP expressed as mean (SD) and defined as the average of 09:00 and 11:00 values.

Abbreviations: BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; BL, baseline; CI, confidence interval; FAS, full analysis set; IOP, intraocular pressure; LS, least square; n, number of patients; SE, standard error; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination.

Figure 4 Mean diurnal intraocular pressure at week 6 (Full analysis set). *BL IOP expressed as mean (SD) and defined as the average of 09:00 and 11:00 values.

Abbreviations: BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; CI, confidence interval; FAS, full analysis set; IOP, intraocular pressure; LS, least squares; n, number of patients; SD, standard deviation; SE, standard error; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination.

Table 2 Adverse Events (Safety Set)

Preferred Term	BBFC+TTFC N=67	Vehicle+TTFC N=67
Any event, n (%)	16 (23.9)	10 (14.9)
Treatment-related AE, n (%)	10 (14.9)	1 (1.5)
Serious AE (Dysuria)	0 (0.0)	1 (1.5)
Ocular AEs (any event)	8 (11.9)	5 (7.5)
Punctate keratitis	2 (3.0)	0 (0.0)
Eye irritation	0 (0.0)	2 (3.0)
Conjunctivitis allergic	1 (1.5)	1 (1.5)
Ocular hyperemia	1 (1.5)	1 (1.5)
Visual acuity reduced	1 (1.5)	1 (1.5)
Ciliary hyperemia	1 (1.5)	0 (0.0)
Drug hypersensitivity	1 (1.5)	0 (0.0)
Eye discharge	1 (1.5)	0 (0.0)
Eye pain	1 (1.5)	0 (0.0)
Eye pruritus	1 (1.5)	0 (0.0)
Foreign body sensation in eyes	1 (1.5)	0 (0.0)
Vision blurred	1 (1.5)	0 (0.0)
Visual field defect	0 (0.0)	1 (1.5)
Non ocular AEs (any event)	12 (17.9)	6 (9.0)
Non ocular AEs (>2%)
Asthenia	2 (3.0)	0 (0.0)
Blood pressure increased	1 (1.5)	2 (3.0)
Nasopharyngitis	1 (1.5)	2 (3.0)

Notes: The higher frequency of AEs observed in the BBFC+TTFC group is likely because these patients received 4 medications compared with 2 medications in the vehicle+TTFC group. A patient with multiple occurrences of an AE under one treatment is counted only once in this AE category for that treatment. A patient with multiple AEs within a primary system organ class is counted only once in that row.

Abbreviations: AE, adverse event; BBFC, brinzolamide 1%/brimonidine 0.2% fixed-dose combination; N, total number of patients; n, number of patients; TTFC, travoprost 0.004%/timolol 0.5% fixed-dose combination