A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease

Figures & data

Figure 1 Schematic representation of the study design.

Figure 2 Subject disposition throughout the study.

Table 1 Subject demographic characteristics (ITT population)

Parameter	OTX-101 0.09%	OTX-101 0.05%	Vehicle	Overall
	N=152	N=151	N=152	N=455
Age
Mean (SD)	59.2 (14.55)	61.9 (13.27)	59.3 (13.75)	60.1 (13.90)
Min, Max	23, 85	23, 91	22, 89	22, 91
Sex, n (%)
Female	122 (80.3)	119 (78.8)	120 (78.9)	361 (79.3)
Male	30 (19.7)	32 (21.2)	32 (21.1)	94 (20.7)
Race, n (%)
White	126 (82.9)	128 (84.8)	120 (78.9)	374 (82.2)
Black	13 (8.6)	11 (7.3)	20 (13.2)	44 (9.7)
Asian	7 (4.6)	8 (5.3)	3 (2.0)	18 (4.0)
Other	6 (3.9)	4 (2.6)	9 (5.9)	19 (4.2)
Ethnicity, n (%)
Not Hispanic/Latino	123 (80.9)	131 (86.8)	122 (80.3)	376 (82.6)
Hispanic/Latino	29 (19.1)	20 (13.2)	30 (19.7)	79 (17.4)

Abbreviations: ITT, intent-to-treat; Min, minimum; Max, maximum.

Figure 3 The mean CFB in total conjunctival lissamine green staining scores by study visit is presented for the vehicle group (open squares), OTX-101 0.05% group (light blue diamonds), and OTX-101 0.09% group (dark blue circles).

Note: Statistically significant reductions in the mean CFB relative to vehicle were observed for OTX-101 0.09% at Day 42 (P=0.048), Day 56 (P=0.029), and Day 84 (P=0.0076) and at Day 84 for the OTX-101 0.05% group (P=0.006).
Abbreviations: CFB, change from baseline; SE, standard error.

Figure 4 The mean CFB in total corneal fluorescein staining scores by study visit is presented for the vehicle group (unshaded bars), OTX-101 0.05% group (light blue shading), and OTX-101 0.09% group (dark blue shading).

Note: Statistically significant reductions in the mean CFB relative to vehicle were observed for OTX-101 0.05% at Day 28 (P=0.0025), Day 42 (P=0.0015), and Day 84 (P=0.024), as well as at Day 28 (P=0.015) and Day 84 (P=0.0003) for the OTX-101 0.09% group.
Abbreviations: CFB, change from baseline; SE, standard error.

Figure 5 Schirmer’s tear test responders.

Notes: The proportion of subjects with a ≥10 mm improvement in Schirmer’s tear test scores at Day 84, as compared to baseline, is presented for the vehicle group (unshaded bars), OTX-101 0.05% group (light blue shading), and OTX-101 0.09% group (dark blue shading). A statistically higher proportion of subjects with a ≥10 mm improvement in Schirmer’s test scores was observed in the OTX-101 0.09% group (P=0.007) relative to vehicle.

Table 2 Safety summary of common ocular and non-ocular treatment-emergent adverse events (safety population)

System organ class	Preferred term	OTX-101 0.09%	OTX-101 0.05%	Vehicle
		N=152	N=151	N=152
Eye disorders, n (%)	Eye irritation	3 (2.0)	2 (1.3)	1 (0.7)
	Lacrimation increased	3 (2.0)	2 (1.3)	1 (0.7)
	Meibomian gland dysfunction	2 (1.3)	0	1 (0.7)
	Conjunctival hemorrhage	1 (0.7)	2 (1.3)	2 (1.3)
	Eye discharge	1 (0.7)	2 (1.3)	0
	Eye pruritus	1 (0.7)	3 (2.0)	4 (2.6)
	Vitreous floaters	1 (0.7)	1 (0.7)	2 (1.3)
	Eye pain	0	0	2 (1.3)
	Eyelid pain	0	2 (1.3)	0
	Vision blurred	0	1 (0.7)	4 (2.6)
	Vitreous detachment	0	3 (2.0)	0
General disorders and administration site conditions, n (%)	Instillation site pain	23 (15.1)	20 (13.2)	5 (3.3)
	Instillation site reaction	0	2 (1.3)	1 (0.7)
Infections and infestations, n (%)	Conjunctivitis viral	0	0	2 (1.3)
Injury, poisoning, and procedural complications, n (%)	Corneal abrasion	0	0	2 (1.3)
Non-ocular events, n (%)	Nasopharyngitis	1 (0.7)	2 (1.3)	4 (2.6)
	Upper respiratory tract infections	3 (2.0)	1 (0.7)	2 (1.3)
	Bronchitis	2 (1.3)	3 (2.0)	2 (1.3)
	Sinusitis	0	3 (2.0)	0

Table 3 Subject’s assessment of the comfort/tolerability of the study medication (safety population)

Time point	Findinga	OTX-101 0.09%	OTX-101 0.05%	Vehicle
		N=152	N=151	N=152
Baseline (Day 0)
3 minutes postinstillation, n (%)	No or mild discomfort	136 (89.5)	134 (88.7)	141 (92.8)
	Worse than mild discomfort	16 (10.5)	17 (11.3)	11 (7.2)
10 minutes postinstillation, n (%)	No or mild discomfort	139 (92.1)b	143 (94.7)	149 (98.0)
	Worse than mild discomfort	12 (7.9)	8 (5.3)	3 (2.0)
Visit 7 (Day 84)
3 minutes postinstillation, n (%)	No or mild discomfort	115 (85.2)	122 (88.4)	128 (92.1)
	Worse than mild discomfort	20 (14.8)	16 (11.6)	11 (7.9)
10 minutes postinstillation, n (%)	No or mild discomfort	125 (92.6)	125 (90.6)	129 (92.8)
	Worse than mild discomfort	10 (7.4)	13 (9.4)	10 (7.2)

Notes:

a Subjects were asked to grade the study medication comfort/tolerability on a 0–3 scale (0= no discomfort; 1= mild discomfort; 2= moderate discomfort; 3= severe discomfort). Responses categorized as “no or mild discomfort” correspond to responses of 0–1, while responses categorized as “worse than mild discomfort” correspond to responses of 2–3.

b P-value calculated between the OTX-101 0.09% and vehicle groups; P=0.0181.