Low‐dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials

Figures & data

Table 1. Summary of studies of brimonidine tartrate ophthalmic solution 0.025 per cent included in this integrated analysis

Study number	Study design	Subjects^†	n^‡	Treatment duration	Analysis
Study 1	Single‐centre, randomised, double‐masked, vehicle‐controlled	Adult and geriatric subjects with ocular redness	Brimonidine: 38	28-days	Efficacy
NCT01675609			Vehicle: 19	QID	Safety
Phase 2/3
Study 2	Single‐centre, randomised, double‐masked, vehicle‐controlled	Adult and geriatric subjects with ocular redness	Brimonidine: 40	28-days	Efficacy
			Vehicle: 20	QID	Safety
NCT01959230
Phase 3
Study 3	Multi‐centre, randomised, double‐masked, vehicle‐controlled	Healthy paediatric, adult, and geriatric subjects	Brimonidine: 335	28-days	Safety
				QID
NCT01959243
			Vehicle: 170
Phase 3
Study 4	Single‐centre, open‐label	Healthy adult subjects	Brimonidine: 13	Single dose, then QID for five-days	Safety
NCT02039765			Vehicle: 0
Pharmacokinetic

QID: four times daily.

† Paediatric: aged at least five-years and no older than 17-years; adult: aged between 18 and 64-years; geriatric: aged more than or equal to 65-years.

‡ Number of randomised subjects who received at least one dose of study medication.

Table 2. Subject demographic characteristics

Characteristic	Efficacy population		Safety population
	Brimonidine 0.025% (n = 78)	Vehicle (n = 39)	Brimonidine 0.025% (n = 426)	Vehicle (n = 209)
Age, years, mean (SD)	52.1 (13.6)	50.7 (12.9)	42.2 (17.0)	42.8 (17.3)
Age group, n (%)
5 to 17-years	0 (0.0)	0 (0.0)	33 (7.7)	17 (8.1)
18 to 64-years	63 (80.8)	32 (82.1)	350 (82.2)	166 (79.4)
At least 65-years	15 (19.2)	7 (17.9)	43 (10.1)	26 (12.4)
Female sex, n (%)	52 (66.7)	30 (76.9)	259 (60.8)	130 (62.2)
Race, n (%)
White	62 (79.5)	26 (66.7)	373 (87.6)	181 (86.6)
Black	14 (17.9)	0 (0.0)	37 (8.7)	20 (9.6)
Asian	1 (1.3)	13 (33.3)	7 (1.6)	3 (1.4)
Other	1 (1.3)	0 (0.0)	9 (2.1)	5 (2.4)
Hispanic ethnicity, n (%)	5 (6.4)	0 (0.0)	42 (9.9)	19 (9.1)
Iris colour
Brown	36 (46.2)	20 (51.3)	204 (47.9)	96 (45.9)
Blue	29 (37.2)	9 (23.1)	113 (26.5)	57 (27.3)
Green	8 (10.3)	4 (10.3)	39 (9.2)	16 (7.7)
Hazel	5 (6.4)	5 (12.8)	69 (16.2)	36 (17.2)
Black	0 (0.0)	1 (2.6)	1 (0.2)	3 (1.4)
Heterochromia	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.5)

SD: standard deviation.

short-legendFigure 1.

short-legendFigure 2.

short-legendFigure 3.

Table 3. Average daily ocular redness scores based on subject diary data (efficacy population)

Ocular redness score^†	Brimonidine 0.025% (n = 78)	Vehicle (n = 39)
Treatment Days 1 to 15
Daily pre‐dose score, mean (SD)	1.3 (0.9)	1.7 (1.0)
Daily post‐dose score, LS mean (SE)	0.8 (0.1)	1.7 (0.1)
LS mean difference (95% CI)^‡	−0.9 (−1.3, −0.6)^*
Treatment Days 15 to 29
Daily pre‐dose score, mean (SD)	1.2 (0.8)	1.6 (1.0)
Daily post‐dose score, LS mean (SE)	0.7 (0.1)	1.5 (0.1)
LS mean difference (95% CI)^‡	−0.9 (−1.2, −0.6)^*

CI: confidence interval, LS: least‐squares (mean), SD: standard deviation, SE: standard error.

* p < 0.0001 versus vehicle.

† Ocular redness was assessed on a scale from 0 to 4; a lower score is indicative of less redness. Mean scores from both eyes were used to calculate the daily average score for each subject. The last observation was carried forward for post‐dose scores. p‐values for active treatment versus vehicle were calculated using a repeated‐measures generalised linear mixed model with treatment and day in the model.

‡ Difference between brimonidine and vehicle.

short-legendFigure 4.

Table 4. Incidence of ocular adverse events occurring in more than one subject in any treatment group (safety population)

	Brimonidine 0.025% (n = 426)	Vehicle (n = 209)
Any ocular adverse event, n (%)	60 (14.1)	28 (13.4)
Eye disorders
Visual acuity reduced	17 (4.0)	9 (4.3)
Conjunctival hyperaemia	11 (2.6)	6 (2.9)
Ocular hyperaemia	5 (1.2)^†	2 (1.0)
Dry eye	5 (1.2)^‡	0 (0.0)
Foreign body sensation	3 (0.7)^§	0 (0.0)
Conjunctival oedema	2 (0.5)	0 (0.0)
Erythema of eyelid	2 (0.5)	0 (0.0)
Eye irritation	2 (0.5)^†	1 (0.5)
Lacrimation increased	1 (0.2)	2 (1.0)^†
Vision blurred	0 (0.0)	2 (1.0)^†
General disorders and administration site conditions
Instillation site pain	7 (1.6)^†	4 (1.9)^†

Medical Dictionary for Regulatory Activities (MedDRA; version 16.1) was used for coding adverse events. Ocular hyperaemia and conjunctival hyperaemia are distinct MedDRA terms, with the latter sometimes chosen in association with slitlamp findings.

† All reports considered treatment‐related.

‡ Three reports considered treatment‐related.

§ One report considered treatment‐related.