OMS302 (phenylephrine and ketorolac injection) 1%/0.3% to maintain intraoperative pupil size and to prevent postoperative ocular pain in cataract surgery with intraocular lens replacement

Figures & data

Table 1. Demographic and subject characteristics.

	Phase II study		Phase III study #1		Phase III study #2
	Vehicle (n = 57)	OMS302 (n = 56)	Vehicle (n = 201)	OMS302 (n = 201)	Vehicle (n = 204)	OMS302 (n = 202)
Age (year)
n	57	56	201	201	204	202
Mean (std)	69 (9.6)	66 (11.2)	69 (9.9)	68 (9.6)	68 (10.6)	69 (9.2)
Median	69.0	68.0	69.0	69.0	69.0	70.0
Min, Max	44, 89	23, 86	39, 89	31, 88	26, 90	39, 87
Gender, n (%)
Male	24 (42.1%)	19 (33.9%)	90 (44.8%)	82 (40.8%)	78 (38.2%)	85 (42.1%)
Female	33 (57.19)	37 (65.1%)	111 (55.2%)	119 (59.2%)	126 (61.8%)	117 (57.9%)
Ethnicity, n (%)
Hispanic or Latino	6 (10.5%)	3 (5.4%)	18 (9.0%)	30 (14.9%)	21 (10.3%)	30 (14.9%)
Not Hispanic or Latino	51 (89.5%)	53 (94.6%)	183 (91.0%)	171 (85.1%)	183 (89.7%)	172 (85.1%)
Race, n (%)
American Indian or Alaska Native	0	0	1 (0.5%)	1 (0.5%)	0	1 (0.5%)
Asian	6 (10.5%)	5 (8.9%)	19 (9.5%)	12 (6.0%)	18 (8.8%)	16 (7.9%)
Black or African American	4 (7.0%)	6 (10.7%)	26 (12.9%)	22 (10.9%)	28 (13.7%)	18 (8.9%)
Native Hawaiian or other Pacific Islander	1 (1.8%)	0	0	0	0	1 (0.5%)
White	46 (80.7%)	45 (80.4%)	155 (77.1%)	165 (82.1%)	158 (77.5%)	165 (81.7%)
Other	0	0	0	1 (0.5%)	0	1 (0.5%)
LOCS II Grade, n (%)
Low (N0, N1)	42 (73.7%)	43 (76.8%)	160 (79.6%)	155 (77.1%)	171 (83.8%)	169 (83.7%)
High (N2, N3)	15 (26.3%)	13 (23.2%)	41 (20.4%)	46 (22.9%)	33 (16.2%)	33 (16.3%)
Iris color, n (%)
Black	0	1 (1.8%)	0	0	1 (0.5%)	0
Blue	13 (23.2%)	23 (41.8%)	50 (24.9%)	59 (29.4%)	58 (28.4%)	63 (31.2%)
Brown	31 (55.4%)	23 (41.8%)	105 (52.2%)	108 (53.7%)	107 (52.5%)	106 (52.5%)
Green	1 (1.8%)	0	2 (1.0%)	1 (0.5%)	4 (2.0%)	2 (1.0%)
Grey	2 (3.6%)	2 (3.6%)	20 (10.0%)	13 (6.5%)	12 (5.9%)	13 (6.4%)
Other	9 (16.1%)	6 (10.9%)	24 (11.9%)	20 (10.0%)	21 (10.3%)	18 (8.9%)
Hazel	0	0	0	0	1 (0.5%)	0
Other eye disease, n (%)
Other eye disease, n (%)	24 (42.9%)	24 (43.6%)	110 (54.7%)	110 (54.7%)	122 (59.8%)	129 (63.9%)
Baseline BCVA (log scale)
n	54	53	198	197	197	199
Mean (Std)	0.44 (0.291)	0.37 (0.290)	0.33 (0.276)	0.29 (0.225)	0.33 (0.220)	0.35 (0.217)
Median	0.40	0.30	0.30	0.30	0.30	0.30
Min, Max	−0.10, 1.50	0.00, 1.30	−0.10, 1.60	−0.20, 1.00	−0.10, 1.60	−0.10, 1.60
Surgery received, n (%)
Refractive lens exchange	0	0	4 (2.0%)	1 (0.5%)	1 (0.5%)	1 (0.5%)
Cataract extraction and lens replacement	56 (100%)	55 (100%)	197 (98.0%)	200 (99.5%)	203 (99.5%)	201 (99.5%)

Table 2. Mean area under the curve analysis of change-from-baseline in pupil diameter (mm) during surgery.

	Phase II Study		Phase III Study #1		Phase III Study #2
	Vehicle (n = 56)	OMS302 (n = 55)	Placebo (n = 201)	OMS302 (n = 201)	Placebo (n = 204)	OMS302 (n = 202)
Mean AUC^†
n	53	49	180	184	200	195
Mean (std)	−0.57 (0.672)	0.12 (0.441)	−0.51 (0.581)	0.07 (0.414)	−0.49 (0.571)	0.09 (0.430)
Median	−0.37	0.12	−0.45	0.08	−0.48	0.08
Min, max	−3.3, 0.6	−1.1, 1.4	−2.9, 2.1	−2.7, 1.3	−2.3, 1.5	−2.2, 2.3
Difference in mean AUC
CMH weighted mean difference (SE)^‡	0.69 (0.11)		0.58 (0.05)		0.59 (0.05)
95% CI	0.47, 0.91		0.47, 0.68		0.49, 0.69
p-value^§	<0.0001		<0.0001		<0.0001

^†AUC is calculated by the trapezoidal rule from the baseline to the last post-base value. Mean AUC is calculated by dividing the AUC by duration from the baseline to the last post-baseline value.

^‡CMH-weighted mean difference (OMS302 – Placebo/Vehicle) is adjusted for the randomization strata.

^§p-value is based on the generalized CMH test stratified by the randomization strata.

Table 3. Intraoperative six millimeter pupil diameter and mean cortical clean up pupil diameter.

	Phase II study		Phase III study #1		Phase III study #2
	Vehicle (n = 56) n (%)	OMS302 (n = 55) n (%)	Placebo (n = 201) n (%)	OMS302 (n = 201) n (%)	Placebo (n = 204) n (%)	OMS302 (n = 202) n (%)
Subjects with <6 mm at cortical cleanup/subjects with video data			41/180 (22.8%)	7/184 (3.8%)	46/200 (23.0%)	8/195 (4.1%)
p-value^†	–	–		<0.0001		<0.0001
Subjects with <6 mm at any time during surgery/subjects with video data	25/53 (47.2%)	3/49 (6.1%)	85/180 (47.2%)	19/184 (10.3%)	76/200 (38.0%)	18/195 (9.2%)
p-value^†		<0.0001		<0.0001		<0.0001
Subjects with degree of pupillary constriction ≥2.5 mm^‡	12/53 (22.6%)	2/49 (4.1%)	50/180 (27.8%)	6/201 (3.3%)	53/200 (26.5%)	2/195 (1.0%)
p-value		<0.0008^§		<0.0001^¶		<0.0001^#
Pupil diameter (mm) at cortical cleanup
n	–	–	180	184	200	195
Mean (SD)	–	–	7.1 (2.0)	8.0 (1.8)	7.5 (2.5)	8.6 (2.4)
Median	–	–	7	8	7	8
Min, max	–	–	3.8, 18.0	2.7, 17.8	3.3, 18.7	4.8, 19.2
p-value^§	–	–		<0.0001		<0.0001

^†Chi-Square test.

^‡Maximum decrease in pupil diameter during surgery.

^§t-test.

^¶Fisher’s exact test.

Table 4. Mean area under the curve analysis of ocular pain visual analog scale score during 12 h postoperatively.

	Phase II study		Phase III study #1		Phase III study #2
	Vehicle (n = 56)	OMS302 (n = 55)	Placebo (n = 201)	OMS302 (n = 201)	Placebo (n = 204)	OMS302 (n = 202)
Mean AUC^†
n	56	55	201	201	202	202
Mean (std)	9.58 (14.100)	4.44 (9.595)	9.22 (12.928)	4.07 (8.072)	8.91 (15.192)	4.25 (8.747)
Median	2.70	0.96	3.00	1.11	2.51	1.00
Min, max	0.0, 55.2	0.0, 56.7	0.0, 65.3	0.0, 66.9	0.0, 85.8	0.0, 58.4
Difference in mean AUC
CMH-weighted mean difference (SE)^‡	−5.13 (2.31)		−5.20 (1.08)		−4.58 (1.19)
95% CI	−9.66, −0.61		−7.31, −3.09		−6.92, −2.24
p-value^§	0.029		<0.001		<0.001

^†AUC is calculated by the trapezoidal rule from the baseline to the last post-base value. Mean AUC is calculated by dividing the AUC by duration from the baseline to the last post-baseline value.

^‡CMH-weighted mean difference (OMS302 - Placebo/Vehicle) is adjusted for the randomization strata.

^§p-value is based on the generalized CMH test stratified by the randomization strata.

AUC: Area-under-the-curve.

Table 5. Subjects reporting no ocular pain and moderate-to-severe ocular pain during 12 h postoperatively.

	Phase II study		Phase III study #1		Phase III study #2
	Vehicle (n = 56) n (%)	OMS302 (n = 55) n (%)	Placebo (n = 201) n (%)	OMS302 (n = 201) n (%)	Placebo (n = 204) n (%)	OMS302 (n = 202) n (%)
Subjects who were pain-free (VAS = 0) at all time points^†
p-value^‡	10/56 (17.9%)	15/55 (27.3%)	28/201 (13.9%)	48/201 (23.9%)	41/202 (20.3%)	56/202 (27.7%)
		0.2351		0.0108		0.0806
Subjects with moderate-to-severe pain (VAS ≥ 40) at any time point
p-value^‡	9/56 (16.1%)	4/55 (7.3%)	30/201 (14.9%)	13/201 (6.5%)	27/202 (13.4%)	16/202 (7.9%)
		0.1495		0.0061		0.0760

^†Subjects with missing VAS during the 12 h postoperatively are considered as not being pain-free.

^‡Chi-square test.

Table 6. Common treatment-emergent adverse events with subject incidence of ≥1% in OMS302 arm in pooled placebo-controlled trial database (Safety Population).

Preferred term	Pooled placebo (n = 462) n (%)	Pooled OMS302 (n = 459) n (%)
Any event	314 (68.0%)	288 (62.7%)
Eye pain	178 (38.5%)	139 (30.3%)
Eye inflammation	67 (14.5%)	74 (16.1%)
Anterior chamber inflammation	35 (7.6%)	37 (8.1%)
Headache	43 (9.3%)	30 (6.5%)
Intraocular pressure increased	15 (3.2%)	20 (4.4%)
Posterior capsule opacification	16 (3.5%)	18 (3.9%)
Photophobia	21 (4.5%)	16 (3.5%)
Ocular discomfort	26 (5.6%)	13 (2.8%)
Conjunctival hyperemia	13 (2.8%)	11 (2.4%)
Corneal edema	13 (2.8%)	11 (2.4%)
Inflammation	13 (2.8%)	11 (2.4%)
Pain	14 (3.0%)	10 (2.2%)
Eye irritation	6 (1.3%)	9 (2.0%)
Conjunctivitis	4 (0.9%)	8 (1.7%)
Foreign body sensation in eyes	11 (2.4%)	8 (1.7%)
Nausea	1 (0.2%)	8 (1.7%)
Back pain	3 (0.6%)	6 (1.3%)
Iritis	3 (0.6%)	5 (1.1%)
Vision blurred	17 (3.7%)	5 (1.1%)