Trial Outcomes & Findings for Safety and Efficacy of Nyxol With Pilocarpine Eye Drops in Subjects With Presbyopia (NCT NCT04675151)

Last Updated: 2025-10-10

Results Overview

The primary efficacy endpoint was the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA on Visit 2 at 1 hour with POS + LDP compared to placebo alone. The improvement in binocular DCNVA for each subject was relative to the subject's own baseline value (Visit 1).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

150 participants

Primary outcome timeframe

Visit 2 at 1 hour

Results posted on

2025-10-10

Participant Flow

Participant milestones

Participant milestones
Measure	POS 0.75% First, Then LDP 0.4% Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Overall Study STARTED	44	30	31	45
Overall Study COMPLETED	43	30	31	44
Overall Study NOT COMPLETED	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	POS 0.75% First, Then LDP 0.4% Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Overall Study Protocol Violation	1	0	0	1

Baseline Characteristics

Safety and Efficacy of Nyxol With Pilocarpine Eye Drops in Subjects With Presbyopia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	POS 0.75% First, Then LDP 0.4% n=43 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=44 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	Total n=148 Participants Total of all reporting groups
Age, Continuous	53.4 years STANDARD_DEVIATION 5.63 • n=5 Participants	52.8 years STANDARD_DEVIATION 5.11 • n=7 Participants	52.7 years STANDARD_DEVIATION 5.21 • n=5 Participants	53.2 years STANDARD_DEVIATION 4.55 • n=4 Participants	53.1 years STANDARD_DEVIATION 5.09 • n=21 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	23 Participants n=7 Participants	18 Participants n=5 Participants	29 Participants n=4 Participants	108 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants	15 Participants n=4 Participants	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	10 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	27 Participants n=7 Participants	29 Participants n=5 Participants	40 Participants n=4 Participants	138 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants	38 Participants n=4 Participants	132 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Study eye, n (%) OD	29 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants	35 Participants n=4 Participants	110 Participants n=21 Participants
Study eye, n (%) OS	14 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	38 Participants n=21 Participants
Iris color, n (%) Light blue	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	20 Participants n=21 Participants
Iris color, n (%) Dark blue	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants
Iris color, n (%) Blue with peripupillary brown	14 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	35 Participants n=21 Participants
Iris color, n (%) Uniform green	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants
Iris color, n (%) Green with brown iris ring	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	17 Participants n=21 Participants
Iris color, n (%) Central brown and peripheral green	8 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	15 Participants n=21 Participants
Iris color, n (%) Brown with some peripheral green	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	14 Participants n=21 Participants
Iris color, n (%) Brown	7 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants	31 Participants n=21 Participants
Irides type, n (%) Light	25 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	26 Participants n=4 Participants	88 Participants n=21 Participants
Irides type, n (%) Dark	18 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	18 Participants n=4 Participants	60 Participants n=21 Participants
Baseline photopic BCDVA study eye, letters read	57.8 letters read at 4 m distance STANDARD_DEVIATION 3.46 • n=5 Participants	57.9 letters read at 4 m distance STANDARD_DEVIATION 2.84 • n=7 Participants	58.1 letters read at 4 m distance STANDARD_DEVIATION 3.00 • n=5 Participants	59.2 letters read at 4 m distance STANDARD_DEVIATION 3.58 • n=4 Participants	58.3 letters read at 4 m distance STANDARD_DEVIATION 3.31 • n=21 Participants
Baseline photopic BCDVA fellow eye	58.5 letters read at 4 m distance STANDARD_DEVIATION 3.12 • n=5 Participants	58.9 letters read at 4 m distance STANDARD_DEVIATION 3.39 • n=7 Participants	57.7 letters read at 4 m distance STANDARD_DEVIATION 3.29 • n=5 Participants	59.3 letters read at 4 m distance STANDARD_DEVIATION 3.69 • n=4 Participants	58.7 letters read at 4 m distance STANDARD_DEVIATION 3.40 • n=21 Participants
Baseline photopic BCDVA binocular	61.0 letters read at 4 m distance STANDARD_DEVIATION 2.97 • n=5 Participants	61.2 letters read at 4 m distance STANDARD_DEVIATION 3.53 • n=7 Participants	60.0 letters read at 4 m distance STANDARD_DEVIATION 3.77 • n=5 Participants	61.4 letters read at 4 m distance STANDARD_DEVIATION 3.560 • n=4 Participants	60.9 letters read at 4 m distance STANDARD_DEVIATION 3.45 • n=21 Participants
Baseline mesopic BCDVA study eye	51.0 letters read at 4 m distance STANDARD_DEVIATION 3.95 • n=5 Participants	49.5 letters read at 4 m distance STANDARD_DEVIATION 6.44 • n=7 Participants	50.6 letters read at 4 m distance STANDARD_DEVIATION 5.83 • n=5 Participants	52.2 letters read at 4 m distance STANDARD_DEVIATION 5.31 • n=4 Participants	51.0 letters read at 4 m distance STANDARD_DEVIATION 5.36 • n=21 Participants
Baseline mesopic BCDVA fellow eye	51.3 letters read at 4 m distance STANDARD_DEVIATION 4.11 • n=5 Participants	50.6 letters read at 4 m distance STANDARD_DEVIATION 6.53 • n=7 Participants	50.2 letters read at 4 m distance STANDARD_DEVIATION 6.14 • n=5 Participants	52.2 letters read at 4 m distance STANDARD_DEVIATION 5.06 • n=4 Participants	51.2 letters read at 4 m distance STANDARD_DEVIATION 5.38 • n=21 Participants
Baseline mesopic BCDVA binocular	54.1 letters read at 4 m distance STANDARD_DEVIATION 3.31 • n=5 Participants	54.2 letters read at 4 m distance STANDARD_DEVIATION 4.93 • n=7 Participants	52.6 letters read at 4 m distance STANDARD_DEVIATION 5.44 • n=5 Participants	54.8 letters read at 4 m distance STANDARD_DEVIATION 4.98 • n=4 Participants	54.0 letters read at 4 m distance STANDARD_DEVIATION 4.68 • n=21 Participants
Baseline photopic DCNVA study eye	41.8 letters read at 4 m distance STANDARD_DEVIATION 5.39 • n=5 Participants	37.9 letters read at 4 m distance STANDARD_DEVIATION 7.23 • n=7 Participants	42.8 letters read at 4 m distance STANDARD_DEVIATION 5.34 • n=5 Participants	42.0 letters read at 4 m distance STANDARD_DEVIATION 5.00 • n=4 Participants	41.3 letters read at 4 m distance STANDARD_DEVIATION 5.90 • n=21 Participants
Baseline photopic DCNVA fellow eye	44.5 letters read at 4 m distance STANDARD_DEVIATION 4.48 • n=5 Participants	42.8 letters read at 4 m distance STANDARD_DEVIATION 6.28 • n=7 Participants	44.7 letters read at 4 m distance STANDARD_DEVIATION 4.61 • n=5 Participants	44.9 letters read at 4 m distance STANDARD_DEVIATION 4.56 • n=4 Participants	44.3 letters read at 4 m distance STANDARD_DEVIATION 4.95 • n=21 Participants
Baseline photopic DCNVA binocular	46.3 letters read at 4 m distance STANDARD_DEVIATION 3.85 • n=5 Participants	45.3 letters read at 4 m distance STANDARD_DEVIATION 5.32 • n=7 Participants	47.6 letters read at 4 m distance STANDARD_DEVIATION 3.49 • n=5 Participants	46.1 letters read at 4 m distance STANDARD_DEVIATION 3.83 • n=4 Participants	46.3 letters read at 4 m distance STANDARD_DEVIATION 4.15 • n=21 Participants
Baseline mesopic DCNVA study eye	36.2 letters read at 4 m distance STANDARD_DEVIATION 7.05 • n=5 Participants	34.6 letters read at 4 m distance STANDARD_DEVIATION 6.81 • n=7 Participants	37.3 letters read at 4 m distance STANDARD_DEVIATION 6.54 • n=5 Participants	36.4 letters read at 4 m distance STANDARD_DEVIATION 6.45 • n=4 Participants	36.2 letters read at 4 m distance STANDARD_DEVIATION 6.71 • n=21 Participants
Baseline mesopic DCNVA fellow eye	38.2 letters read at 4 m distance STANDARD_DEVIATION 6.59 • n=5 Participants	37.3 letters read at 4 m distance STANDARD_DEVIATION 6.92 • n=7 Participants	38.1 letters read at 4 m distance STANDARD_DEVIATION 6.35 • n=5 Participants	37.3 letters read at 4 m distance STANDARD_DEVIATION 6.70 • n=4 Participants	37.7 letters read at 4 m distance STANDARD_DEVIATION 6.59 • n=21 Participants
Baseline mesopic DCNVA binocular	41.4 letters read at 4 m distance STANDARD_DEVIATION 5.99 • n=5 Participants	40.4 letters read at 4 m distance STANDARD_DEVIATION 6.36 • n=7 Participants	40.1 letters read at 4 m distance STANDARD_DEVIATION 6.41 • n=5 Participants	40.3 letters read at 4 m distance STANDARD_DEVIATION 6.05 • n=4 Participants	40.6 letters read at 4 m distance STANDARD_DEVIATION 6.13 • n=21 Participants
Baseline photopic DCIVA study eye	47.4 letters read STANDARD_DEVIATION 6.87 • n=5 Participants	45.3 letters read STANDARD_DEVIATION 8.04 • n=7 Participants	46.9 letters read STANDARD_DEVIATION 6.34 • n=5 Participants	46.0 letters read STANDARD_DEVIATION 6.39 • n=4 Participants	46.5 letters read STANDARD_DEVIATION 6.86 • n=21 Participants
Baseline photopic DCIVA fellow eye	48.7 letters read STANDARD_DEVIATION 6.68 • n=5 Participants	49.1 letters read STANDARD_DEVIATION 7.01 • n=7 Participants	48.4 letters read STANDARD_DEVIATION 5.10 • n=5 Participants	48.3 letters read STANDARD_DEVIATION 6.19 • n=4 Participants	48.6 letters read STANDARD_DEVIATION 6.25 • n=21 Participants
Baseline photopic DCIVA binocular	51.3 letters read STANDARD_DEVIATION 6.42 • n=5 Participants	52.6 letters read STANDARD_DEVIATION 7.45 • n=7 Participants	50.9 letters read STANDARD_DEVIATION 4.87 • n=5 Participants	51.5 letters read STANDARD_DEVIATION 6.14 • n=4 Participants	51.5 letters read STANDARD_DEVIATION 6.24 • n=21 Participants
Baseline photopic PD study eye	4.297 mm STANDARD_DEVIATION 0.8347 • n=5 Participants	4.494 mm STANDARD_DEVIATION 0.8190 • n=7 Participants	4.342 mm STANDARD_DEVIATION 0.9966 • n=5 Participants	4.265 mm STANDARD_DEVIATION 0.8782 • n=4 Participants	4.337 mm STANDARD_DEVIATION 0.8756 • n=21 Participants
Baseline photopic PD fellow eye	4.267 mm STANDARD_DEVIATION 0.8277 • n=5 Participants	4.608 mm STANDARD_DEVIATION 0.9048 • n=7 Participants	4.391 mm STANDARD_DEVIATION 0.9617 • n=5 Participants	4.340 mm STANDARD_DEVIATION 0.8299 • n=4 Participants	4.384 mm STANDARD_DEVIATION 0.8731 • n=21 Participants
Baseline mesopic PD study eye	5.059 mm STANDARD_DEVIATION 0.8747 • n=5 Participants	5.049 mm STANDARD_DEVIATION 0.7324 • n=7 Participants	4.992 mm STANDARD_DEVIATION 1.1530 • n=5 Participants	5.113 mm STANDARD_DEVIATION 0.8310 • n=4 Participants	5.059 mm STANDARD_DEVIATION 0.8942 • n=21 Participants
Baseline mesopic PD fellow eye	5.136 mm STANDARD_DEVIATION 0.8759 • n=5 Participants	5.100 mm STANDARD_DEVIATION 0.6839 • n=7 Participants	4.996 mm STANDARD_DEVIATION 1.1266 • n=5 Participants	5.197 mm STANDARD_DEVIATION 0.8201 • n=4 Participants	5.117 mm STANDARD_DEVIATION 0.8789 • n=21 Participants
Baseline IOP study eye	14.4 mmHg STANDARD_DEVIATION 3.40 • n=5 Participants	14.8 mmHg STANDARD_DEVIATION 3.14 • n=7 Participants	13.9 mmHg STANDARD_DEVIATION 2.54 • n=5 Participants	13.6 mmHg STANDARD_DEVIATION 2.88 • n=4 Participants	14.1 mmHg STANDARD_DEVIATION 3.03 • n=21 Participants
Baseline IOP fellow eye	14.3 mmHg STANDARD_DEVIATION 2.99 • n=5 Participants	14.9 mmHg STANDARD_DEVIATION 2.94 • n=7 Participants	14.1 mmHg STANDARD_DEVIATION 2.41 • n=5 Participants	13.8 mmHg STANDARD_DEVIATION 2.85 • n=4 Participants	14.3 mmHg STANDARD_DEVIATION 2.83 • n=21 Participants

PRIMARY outcome

Timeframe: Visit 2 at 1 hour

Outcome measures

Outcome measures
Measure	POS 0.75% First, Then LDP 0.4% n=43 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=44 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA	60.5 percentage of subjects with ≥ 15 letters	30.0 percentage of subjects with ≥ 15 letters	45.2 percentage of subjects with ≥ 15 letters	27.3 percentage of subjects with ≥ 15 letters

SECONDARY outcome

Timeframe: Visit 2 at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours

The percentage of subjects with improvement of ≥ 5, ≥ 10, and ≥ 15 letters in DCNVA (photopic) from Baseline at 0.5 hours, at 2 hours, at 3 hours, at 4 hours, and at 6 hours

Outcome measures

SECONDARY outcome

Timeframe: Visit 2 at 1 hour

The percentage of subjects with improvement of ≥ 15 letters in DCNVA (photopic) at 1 hour and with \< 5 letters of loss in photopic binocular BCDVA from Baseline

Outcome measures

Outcome measures
Measure	POS 0.75% First, Then LDP 0.4% n=43 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=44 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Percentage of Subjects With Improvement of ≥ 15 Letters in DCNVA (Photopic) at 1 Hour and With < 5 Letters of Loss in Photopic Binocular BCDVA From Baseline	60.5 % of subjects with improvement	30.0 % of subjects with improvement	41.9 % of subjects with improvement	27.93 % of subjects with improvement

SECONDARY outcome

Timeframe: Visit 2 at 1 hour, at 3 hours, and at 6 hours

The percentage of subjects with improvement in DCIVA (photopic) from Baseline of ≥ 5, ≥ 10, and ≥ 15 letters

Outcome measures

Outcome measures
Measure	POS 0.75% First, Then LDP 0.4% n=43 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=44 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 6 hours	72.1 percentage with improvement	56.7 percentage with improvement	38.7 percentage with improvement	47.7 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 1 hour	86.0 percentage with improvement	46.7 percentage with improvement	71.0 percentage with improvement	56.8 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 1 hour	48.8 percentage with improvement	23.3 percentage with improvement	45.2 percentage with improvement	25.0 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 1 hour	14.0 percentage with improvement	10.0 percentage with improvement	22.6 percentage with improvement	4.5 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 3 hours	69.8 percentage with improvement	43.3 percentage with improvement	67.7 percentage with improvement	50.0 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 3 hours	41.9 percentage with improvement	30.0 percentage with improvement	41.9 percentage with improvement	25.0 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 3 hours	18.6 percentage with improvement	10.0 percentage with improvement	22.6 percentage with improvement	4.5 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 6 hours	30.2 percentage with improvement	16.7 percentage with improvement	29.0 percentage with improvement	18.2 percentage with improvement
Percentage of Subjects With Improvement in DCIVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 6 hours	14.0 percentage with improvement	10.0 percentage with improvement	12.9 percentage with improvement	4.5 percentage with improvement

Adverse Events

POS 0.75% First, Then LDP 0.4%

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

POS 0.75% First, Then LDP Vehicle

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

POS Vehicle First, Then LDP 0.4%

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

POS Vehicle First, Then LDP Vehicle

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Drey Coleman

Ocuphire Pharma, Inc.

Phone: 8134041993

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	POS 0.75% First, Then LDP 0.4% n=43 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 Participants Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=44 Participants Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 0.5 hours	88.4 percentage of subjects with improvement	86.7 percentage of subjects with improvement	74.2 percentage of subjects with improvement	70.5 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 0.5 hours	76.7 percentage of subjects with improvement	50.0 percentage of subjects with improvement	54.8 percentage of subjects with improvement	52.3 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 0.5 hours	60.5 percentage of subjects with improvement	33.3 percentage of subjects with improvement	25.8 percentage of subjects with improvement	15.9 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 2 hours	88.4 percentage of subjects with improvement	93.3 percentage of subjects with improvement	83.9 percentage of subjects with improvement	70.5 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 2 hours	81.4 percentage of subjects with improvement	60.0 percentage of subjects with improvement	71.0 percentage of subjects with improvement	45.5 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 2 hours	62.8 percentage of subjects with improvement	26.7 percentage of subjects with improvement	41.9 percentage of subjects with improvement	18.2 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 3 hours	95.3 percentage of subjects with improvement	83.3 percentage of subjects with improvement	83.9 percentage of subjects with improvement	72.7 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 3 hours	67.4 percentage of subjects with improvement	60.0 percentage of subjects with improvement	64.5 percentage of subjects with improvement	43.2 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 3 hours	46.5 percentage of subjects with improvement	26.7 percentage of subjects with improvement	48.4 percentage of subjects with improvement	20.5 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 4 hours	95.3 percentage of subjects with improvement	83.3 percentage of subjects with improvement	83.9 percentage of subjects with improvement	75.0 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 4 hours	67.4 percentage of subjects with improvement	60.0 percentage of subjects with improvement	51.6 percentage of subjects with improvement	50.0 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 4 hours	46.5 percentage of subjects with improvement	30.0 percentage of subjects with improvement	32.3 percentage of subjects with improvement	20.5 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 5 letters from baseline at 6 hours	88.4 percentage of subjects with improvement	86.7 percentage of subjects with improvement	71.0 percentage of subjects with improvement	72.7 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 10 letters from baseline at 6 hours	67.4 percentage of subjects with improvement	60.0 percentage of subjects with improvement	54.8 percentage of subjects with improvement	50.0 percentage of subjects with improvement
Percentage of Subjects With Improvement of ≥ 5, ≥ 10, and ≥ 15 Letters in DCNVA (Photopic) From Baseline % of subjects with improvement of ≥ 15 letters from baseline at 6 hours	37.2 percentage of subjects with improvement	36.7 percentage of subjects with improvement	22.6 percentage of subjects with improvement	18.2 percentage of subjects with improvement

Measure	POS 0.75% First, Then LDP 0.4% n=44 participants at risk Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS 0.75% First, Then LDP Vehicle n=30 participants at risk Participants received Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of 0.75% POS, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (0.75% POS) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP 0.4% n=31 participants at risk Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine: 0.4% Pilocarpine ophthalmic solution, a direct-acting cholinergic agonist at Visit 2. Treatment 1 (Nyxol or placebo) was administered in both eyes (OU)by the subject. Treatment 2 was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (0.4% LDP) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.	POS Vehicle First, Then LDP Vehicle n=45 participants at risk Participants received Phentolamine Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution, starting on the night of Visit 1 and subsequently taken daily for 3 to 4 consecutive days immediately prior to Visit 2. Then, after 3-4 days of initial administration of POS Vehicle, participants received Low-Dose Pilocarpine Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. Treatment 1 (POS Vehicle) was administered in both eyes (OU) by the subject. Treatment 2 (LDP Vehicle) was administered OU by a designated, unmasked site staff member, distinct from the site staff member recording assessments.
General disorders Instillation site erythema	13.6% 6/44 • Number of events 6 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	10.0% 3/30 • Number of events 3 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	6.5% 2/31 • Number of events 2 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
General disorders Installation site pain	9.1% 4/44 • Number of events 4 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	10.0% 3/30 • Number of events 3 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	2.2% 1/45 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
General disorders Installation site pruritus	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Conjunctival hyperaemia	4.5% 2/44 • Number of events 2 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	6.7% 2/30 • Number of events 2 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Corneal dystrophy	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Eye irritation	6.8% 3/44 • Number of events 3 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Eye pain	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.2% 1/31 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Eye pruritus	0.00% 0/44 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.2% 1/31 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Foreign body sensation in eyes	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Lacrimation increased	4.5% 2/44 • Number of events 2 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Eye disorders Visual acuity reduced	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.3% 1/30 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	6.5% 2/31 • Number of events 2 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	2.2% 1/45 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Gastrointestinal disorders Dysgeusia	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.3% 1/30 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Investigations Intraocular pressure increased	0.00% 0/44 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.2% 1/31 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Nervous system disorders Headache	0.00% 0/44 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	3.2% 1/31 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Respiratory, thoracic and mediastinal disorders Throat irritation	2.3% 1/44 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/45 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.
Vascular disorders Hypertension	0.00% 0/44 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/30 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	0.00% 0/31 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.	2.2% 1/45 • Number of events 1 • 9 days. Data is not provided for each intervention separately as analyses by specific intervention were not conducted.