Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies

Figures & data

Figure 1 Participant flow.

Notes: ^aBased on the intent-to-treat population. Reasons for discontinuations are primary reasons for withdrawal from the intent-to-treat population.

Abbreviation: LE, loteprednol etabonate; TID, three times daily.

Table 1 Subject demographics for the integrated dataset

Parameter	ITT population
	LE gel 0.38% TID (n=371)	Vehicle (n=371)	Overall (N=742)
Age (years)
Mean (SD)	69.1 (8.88)	68.7 (8.75)	68.9 (8.81)
Median	70.0	69.0	70.0
Range	36, 92	38, 88	36, 92
Sex, n (%)
Male	152 (41.0)	155 (41.8)	307 (41.4)
Female	219 (59.0)	216 (58.2)	435 (58.6)
Race, n (%)
White	288 (77.6)	288 (77.6)	576 (77.6)
Black/African American	45 (12.1)	38 (10.2)	83 (11.2)
Asian	27 (7.3)	30 (8.1)	57 (7.7)
Native Hawaiian/Pacific Islander	1 (0.3)	2 (0.5)	3 (0.4)
American Indian/Alaskan Native	2 (0.5)	0	2 (0.3)
Other	6 (1.6)	12 (3.2)	18 (2.4)
Multiple races	2 (0.5)	1 (0.3)	3 (0.4)

Abbreviations: ITT, intent-to-treat; LE, loteprednol etabonate; TID, three times daily.

Figure 2 Percentage of subjects with complete resolution of AC cells and grade 0 pain at day 8 (visit 5) in the ITT population.

Note: ^aPearson Chi-squared test P<0.0001 vs vehicle.

Abbreviations: AC, anterior chamber; ITT, intent-to-treat; LE, loteprednol etabonate; TID, three times daily.

Table 2 Proportion of subjects with complete resolution of AC cells, flare, AC cells and flare combined, and grade 0 (no) pain 3–18 days postoperatively (ITT population, missing values, and post-rescue values imputed as treatment failures)

Study day/endpoint	LE gel 0.38% TID (n=371) n (%)	Vehicle (n=371) n (%)	Diff vs vehicle, % (95% CI)	P-value^b
Day 3
Complete resolution of AC cells	16 (4.3)	21 (5.7)	-1.3 (-4.5–1.8)	0.3391
Grade 0 (no) pain	266 (71.7)	187 (50.4)	21.3 (14.4–28.1)	<0.0001
Complete resolution of AC flare	197 (53.1)	156 (42.0)	11.1 (3.9–18.2)	0.0026
Complete resolution AC cells and flare	16 (4.3)	19 (5.1)	-0.8 (−3.9–2.2)	0.6034
Day 8
Complete resolution of AC cells^a	110 (29.6)	56 (15.1)	14.6 (8.7–20.5)	<0.0001
Grade 0 (no) pain^a	276 (74.4)	181 (48.8)	25.6 (18.9–32.4)	<0.0001
Complete resolution of AC flare	253 (68.2)	147 (39.6)	28.6 (21.7–35.4)	<0.0001
Complete resolution AC cells and flare	101 (27.2)	51 (13.7)	13.5 (7.8–19.2)	<0.0001
Day 15
Complete resolution of AC cells	176 (47.4)	92 (24.8)	22.6 (15.9–29.4)	<0.0001
Grade 0 (no) pain	295 (79.5)	186 (50.1)	29.4 (22.8–35.9)	<0.0001
Complete resolution of AC flare	277 (74.7)	168 (45.3)	29.4 (22.7–36.1)	<0.0001
Complete resolution AC cells and flare	174 (46.9)	90 (24.3)	22.6 (15.9–29.3)	<0.0001
Day 18
Complete resolution of AC cells	186 (50.1)	113 (30.5)	19.7 (12.8–26.6)	<0.0001
Grade 0 (no) pain	267 (72.0)	180 (48.5)	23.5 (16.6–30.3)	<0.0001
Complete resolution of AC flare	266 (71.7)	176 (47.4)	24.3 (17.4–31.1)	<0.0001
Complete resolution AC cells and flare	181 (48.8)	113 (30.5)	18.3 (11.4–25.2)	<0.0001

Notes: ^aPrimary endpoints, ^bP-value from Pearson χ² tests, with missing data and subjects placed on rescue medication imputed as treatment failures.

Abbreviations: AC, anterior chamber; ITT, intent-to-treat; LE, loteprednol etabonate; TID, three times daily.

Figure 3 (A) Mean (SD) change from baseline in anterior chamber cells (ITT population). (B) Mean (SD) change from baseline in anterior chamber flare (ITT population). (C) Mean (SD) change from baseline in anterior chamber cells and flare combined (ITT population).

Notes: ^aP<0.01 vs vehicle; ^bP<0.0001 vs vehicle. Negative values denote improvement. Missing values and post-rescue values were imputed using LOCF, and data were analyzed using a Cochran-Mantel-Haenszel mean score test.

Abbreviations: LE, loteprednol etabonate; ITT, intent-to-treat; LOCF, last observation carried forward; TID, three times daily.

Table 3 Treatment-related ocular AEs (safety population)

	LE gel 0.38% TID (n=369) n (%)	Vehicle (n=370) n (%)
Subjects with ≥1 ocular AE considered treatment related	3 (0.8)	10 (2.7)
Eye disorders
Conjunctival hyperemia	0	2 (0.5)
Corneal edema	0	3 (0.8)
Eye pain	0	2 (0.5)
Photophobia	1 (0.3)	0
Cystoid macular edema	1 (0.3)	0
Eyelid edema	1 (0.3)	0
Ocular discomfort	0	1 (0.3)
General disorders and administration site conditions
Pain	0	1 (0.3)
Instillation site pain	1 (0.3)	0
Foreign body sensation	0	1 (0.3)^a

Notes: ^aThe preferred term for one of these reports was “Instillation site foreign body sensation”. Subjects who reported more than 1 AE were counted only once.

Abbreviations: AE, adverse event; LE, loteprednol etabonate; TID, three times daily.