Safety of Once-Daily Oxymetazoline HCl Ophthalmic Solution, 0.1% in Patients with Acquired Blepharoptosis: Results from Four Randomized, Double-Masked Clinical Trials

Figures & data

Table 1 Participant Disposition, Demographics, Treatment Exposure, and Compliance, by Treatment Group

	Oxymetazoline 0.1% (n=375)	Vehicle (n=193)
Participants completing all study visits, n (%)	356 (94.9)	188 (97.4)
Compliance with treatment, mean (SD)^a
Phase 3 studies (n=358 once-daily oxymetazoline 0.1%; n=178 once-daily vehicle)	98.5 (11.81)	97.1 (9.11)
Phase 1/2a study (n=15 once-daily oxymetazoline 0.1%; n=15 vehicle)	97.3 (5.55)	97.1 (6.77)
Treatment exposure, mean days (SD)	56.4 (24.01)	56.4 (24.02)
Age (years)
Mean (SD)	63.9 (13.78)	62.9 (14.45)
Median	67.0	65.0
Min, Max	13, 92	14, 90
Age group, n (%)
9–17 years	2 (0.5%)	2 (1.0%)
18–50 years	54 (14.4%)	32 (16.6%)
51–64 years	103 (27.5%)	60 (31.1%)
65–75 years	147 (39.2%)	69 (35.8%)
>75 years	69 (18.4%)	30 (15.5%)
Sex, n (%)
Female	290 (77.3%)	135 (69.9%)
Male	85 (22.7%)	58 (30.1%)
Race, n (%)
White	329 (87.7%)	170 (88.1%)
Black	30 (8.0%)	16 (8.3%)
Asian	12 (3.2%)	7 (3.6%)
American Indian	2 (0.5%)	0
Pacific Islander	2 (0.5%)	0
Ethnicity, n (%)
Not Hispanic/Latino	317 (84.5%)	162 (83.9%)
Hispanic/Latino	58 (15.5%)	31 (16.1%)

Notes: Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days, and randomized to self-administer oxymetazoline 0.1% once daily or vehicle. Includes participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020.⁴¹ In the 2-week phase 1/2a study (RVL-1201-001), participants self-administered a single drop of oxymetazoline 0.1% once daily, oxymetazoline 0.1% twice daily, or vehicle twice daily, to both eyes, and study visits occurred at screening and treatment days 1, 7, and 14. In the phase 3 trials, oxymetazoline 0.1% or vehicle was self-administered as a single drop once daily, in both eyes, for the duration of the study. As previously described, in the 6-week phase 3 efficacy studies (RVL-1201-201 and RVL-1201-202), study visits occurred at screening and days 1, 14, and 42.⁴¹ In the phase 3 safety study (RVL-1201-203), study visits occurred at screening and days 1, 14, 42, and 84. ^aCompliance corresponds to the percentage of opened vials returned relative to the number of vials that should have been used during the treatment period.

Abbreviations: Max, maximum; Min, minimum; SD, standard deviation.

Figure 1 Mean ± standard deviation (A) intraocular pressure (IOP), (B) pupil diameter, and (C) Snellen visual acuity (VA) at selected time points. Results shown are for OD. Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days, except IOP, which presents data from N=538 participants enrolled in three phase 3 trials ranging in duration from 42 to 84 days. Includes data from participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020.⁴¹ In the phase 1/2a study, pupil diameter and Snellen VA were evaluated at screening and on treatment days 1 and 14, and IOP was evaluated at screening and on treatment days 7 and 14. As previously reported, in the phase 3 efficacy trials, pupil diameter and Snellen VA were evaluated at all study visits, and IOP was evaluated at screening and on treatment day 42. In the phase 3 safety trial, pupil diameter and Snellen VA were evaluated at all study visits, and IOP was evaluated at baseline/screening and on treatment days 42 and 84.

Table 2 Summary of Treatment-Emergent Adverse Events (TEAEs)

		Oxymetazoline 0.1% (n=375)	Vehicle (n=193)
Participants reporting any TEAE, n (%)	Overall	117 (31.2%)	59 (30.6%)
	Age group, n (%)
	9–17 Years (n=2/2)^a	1 (50.0%)	2 (100.0%)
	18–50 Years (n=54/32)	16 (29.6%)	5 (15.6%)
	51–64 Years (n=103/60)	35 (34.0%)	14 (23.3%)
	65–75 Years (n=147/69)	44 (29.9%)	24 (34.8%)
	>75 Years (n=69/30)	21 (30.4%)	14 (46.7%)
	Race, n (%)
	White (n=329/170)	100 (30.4%)	55 (32.4%)
	Non-white (n=46/23)	17 (37.0%)	4 (17.4%)
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	105 (33.1%)	51 (31.5%)
	Hispanic/Latino (n=58/31)	12 (20.7%)	8 (25.8%)
Participants reporting any TEAE leading to discontinuation from study, n (%)	Overall	9 (2.4%)	2 (1.0%)
	Age group, n (%)
	9–17 Years (n=2/2)	0	0
	18–50 Years (n=54/32)	2 (3.7%)	1 (3.1%)
	51–64 Years (n=103/60)	2 (1.9%)	0
	65–75 Years (n=147/69)	4 (2.7%)	0
	>75 Years (n=69/30)	1 (1.4%)	1 (3.3%)
	Race, n (%)
	White (n=329/170)	8 (2.4%)	2 (1.2%)
	Non-white (n=46/23)	1 (2.2%)	0
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	9 (2.8%)	0
	Hispanic/Latino (n=58/31)	0	2 (6.5%)
Participants reporting any serious TEAE, n (%)	Overall	4 (1.1%)	1 (0.5%)
	Age group, n (%)
	9–17 Years (n=2/2)	0	0
	18–50 Years (n=54/32)	0	0
	51–64 Years (n=103/60)	2 (1.9%)	0
	65–75 Years (n=147/69)	1 (0.7%)	0
	>75 Years (n=69/30)	1 (1.4%)	1 (3.3%)
	Race, n (%)
	White (n=329/170)	4 (1.2%)	1 (0.6%)
	Non-white (n=46/23)	0	0
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	4 (1.3%)	0
	Hispanic/Latino (n=58/31)	0	1 (3.2%)

Notes: Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days. Includes participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020.⁴¹ aFor each participant subgroup, (n=x/y) represents the number participants receiving oxymetazoline 0.1% and vehicle, respectively.

Abbreviation: TEAE, treatment-emergent adverse event.

Table 3 Summary of Serious Treatment-Emergent Adverse Events (TEAEs)

Serious TEAE (MedDRA Preferred Term)	Treatment Group	Details
Arthralgia	Oxymetazoline 0.1%	● 62-year-old white female with a history of hip replacement who developed arthralgia in the same hip ● Severe, not suspected of being treatment-related and resolved following revision surgery; completed study
Cerebrovascular accident^a	Oxymetazoline 0.1%	● 86-year-old white male with a history of hypertension ● Vital signs at predefined study visits:  ● Treatment day 1 (baseline): HR: 80 bpm, SBP: 138 mmHg, DBP: 80 mmHg  ● Treatment day 1 (8 hours post-dose): HR: 74 bpm; SBP: 140 mmHg; DBP: 90 mmHg  ● Treatment day 14 (pre-dose): HR: 78 bpm; SBP: 144 mmHg; DBP: 80 mmHg  ● Treatment day 14 (8 hours post-dose): HR: 78 bpm; SBP: 160 mmHg; DBP: 88 mmHg  ● End of study: HR: 74 bpm; SBP: 148 mmHg; DBP: 80 mmHg ● Mild, not suspected of being treatment-related, and was resolved; completed study
Hyperparathyroidism^a	Oxymetazoline 0.1%	● 73-year-old white female hospitalized for elective parathyroidectomy due to a history of hyperparathyroidism ● Severe, not suspected of being treatment-related, and resolved after surgery; completed study
Nephrolithiasis	Oxymetazoline 0.1%	● 63-year-old white female ● Severe, not suspected of being treatment-related, and considered resolved with sequelae following hospitalization and right-sided ureteroscopic laser lithotripsy and stone removal, and right-sided retrograde pyelogram and stent placement; completed study
Lower gastrointestinal hemorrhage^a	Vehicle	● Occurred in an 83-year-old white female ● Moderate, not suspected of being treatment-related, and resolved after hospitalization and treatment; withdrawn from study

Notes: Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days. Includes participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020. ^aSerious TEAE in a participant enrolled in 6-week phase 3 efficacy trial and previously noted in Slonim et al 2020.⁴¹.

Abbreviations: DBP, diastolic blood pressure; HR, heart rate; MedDRA, Medical Dictionary for Regulatory Activities; SBP, systolic blood pressure; TEAE, treatment-emergent adverse event.

Table 4 Most Common Treatment-Emergent Adverse Events (TEAEs; Occurring in >1% of Patients in Either Treatment Arm)

TEAE, by SOC and MedDRA Preferred Term, n (%)	Oxymetazoline 0.1% (n=375)	Vehicle (n=193)
Eye disorders	74 (19.7%)	26 (13.5%)
Punctate keratitis	13 (3.5%)	4 (2.1%)
Conjunctival hyperemia	11 (2.9%)	1 (0.5%)
Dry eye	9 (2.4%)	1 (0.5%)
Vision blurred	8 (2.1%)	0
Eye irritation	4 (1.1%)	0
Eye pruritus	1 (0.3%)	3 (1.6%)
General disorders and administration site conditions	13 (3.5%)	4 (2.1%)
Instillation site pain	8 (2.1%)	0
Instillation site complication	1 (0.3%)	3 (1.6%)
Infections and infestations	16 (4.3%)	13 (6.7%)
Nasopharyngitis	3 (0.8%)	3 (1.6%)
Upper respiratory tract infection	3 (0.8%)	3 (1.6%)
Investigations	9 (2.4%)	6 (3.1%)
Vital dye staining cornea present	8 (2.1%)	4 (2.1%)
Nervous system disorders	11 (2.9%)	4 (2.1%)
Headache	8 (2.1%)	2 (1.0%)

Notes: TEAEs were coded by SOC and Preferred Term in accordance with the Medical Dictionary for Regulatory Activities (MedDRA). Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days. Includes participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020.⁴¹

Abbreviations: MedDRA, Medical Dictionary for Regulatory Activities; SOC, System Organ Class; TEAE, treatment-emergent adverse event.

Table 5 Relationship to Treatment and Severity of Treatment-Emergent Adverse Events (TEAEs)

		Oxymetazoline 0.1% (n=375)	Vehicle (n=193)
Participants reporting maximum TEAE severity of MILD, n (%)^a	Overall	88 (23.5%)	41 (21.2%)
	Age group, n (%)
	9–17 Years (n=2/2)^b	0	2 (100.0%)
	18–50 Years (n=54/32)	12 (22.2%)	3 (9.4%)
	51–64 Years (n=103/60)	25 (24.3%)	11 (18.3%)
	65–75 Years (n=147/69)	34 (23.1%)	17 (24.6%)
	>75 Years (n=69/30)	17 (24.6%)	8 (26.7%)
	Race, n (%)
	White (n=329/170)	77 (23.4%)	37 (21.8%)
	Non-white (n=46/23)	11 (23.9%)	4 (17.4%)
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	76 (24.0%)	36 (22.2%)
	Hispanic/Latino (n=58/31)	12 (20.7%)	5 (16.1%)
Participants reporting maximum TEAE severity of MODERATE, n (%)	Overall	24 (6.4%)	18 (9.3%)
	Age group, n (%)
	9–17 Years (n=2/2)	1 (50.0%)	0
	18–50 Years (n=54/32)	4 (7.4%)	2 (6.3%)
	51–64 Years (n=103/60)	6 (5.8%)	3 (5.0%)
	65–75 Years (n=147/69)	9 (6.1%)	7 (10.1%)
	>75 Years (n=69/30)	4 (5.8%)	6 (20.0%)
	Race, n (%)
	White (n=329/170)	18 (5.5%)	18 (10.6%)
	Non-white (n=46/23)	6 (13.0%)	0
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	24 (7.6%)	15 (9.3%)
	Hispanic/Latino (n=58/31)	0	3 (9.7%)
Participants reporting maximum TEAE severity of SEVERE, n (%)^c	Overall	5 (1.3%)	0
	Age group, n (%)
	9–17 Years (n=2/2)	0	0
	18–50 Years (n=54/32)	0	0
	51–64 Years (n=103/60)	4 (3.9%)	0
	65–75 Years (n=147/69)	1 (0.7%)	0
	>75 Years (n=69/30)	0	0
	Race, n (%)
	White (n=329/170)	5 (1.5%)	0
	Non-white (n=46/23)	0	0
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	5 (1.6%)	0
	Hispanic/Latino (n=58/31)	0	0
Participants reporting ≥1 TEAE suspected of being treatment-related, n (%)	Overall	47 (12.5%)	15 (7.8%)
	Age group, n (%)
	9–17 Years (n=2/2)	0	0
	18–50 Years (n=54/32)	9 (16.7%)	0
	51–64 Years (n=103/60)	14 (13.6%)	5 (8.3%)
	65–75 Years (n=147/69)	17 (11.6%)	6 (8.7%)
	>75 Years (n=69/30)	7 (10.1%)	4 (13.3%)
	Race, n (%)
	White (n=329/170)	39 (11.9%)	14 (8.2%)
	Non-white (n=46/23)	8 (17.4%)	1 (4.3%)
	Ethnicity, n (%)
	Not Hispanic/Latino (n=317/162)	45 (14.2%)	15 (9.3%)
	Hispanic/Latino (n=58/31)	2 (3.4%)	0

Notes: Data from N=568 participants enrolled in four oxymetazoline 0.1% clinical trials ranging in duration from 14 to 84 days. Includes participants from two phase 3 efficacy studies 42 days in duration with data previously reported by Slonim et al 2020.⁴¹ aMild TEAE = discomfort but no disruption of normal daily activity; Moderate TEAE = discomfort sufficient to cause interference with normal daily activity; Severe TEAE = discomfort that is incapacitating, resulting in inability to perform normal activities. ^bFor each participant subgroup, (n=x/y) represents the number participants receiving oxymetazoline, 0.1% and vehicle, respectively. ^cAll TEAEs assessed as severe were non-ocular and all were judged to be non-treatment related by site investigators.

Abbreviation: TEAE, treatment-emergent adverse event.

Slonim CB, Foster S, Jaros M, et al. Association of oxymetazoline hydrochloride, 0.1%, solution administration with visual field in acquired ptosis: a pooled analysis of 2 randomized clinical trials. JAMA Ophthalmol. 2020;138:1168–1175. doi:10.1001/jamaophthalmol.2020.3812

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