Safety and Efficacy of Ophthalmic Phentolamine Mesylate to Reverse Pharmacologically Induced Mydriasis

• Sponsor: Ocuphire Pharma, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04024891
• Collaborator: (none)
• Enrollment: 32
• Locations: 4
• Arms: 2
• Actual Duration (Months): 1.1
• Patients Per Site: 8
• Patients Per Site Per Month: 7

Study Details

Study Description

Brief Summary

The objectives of this study are:

• To evaluate the efficacy of Nyxol (phentolamine mesylate ophthalmic solution 1%) to expedite the reversal of pharmacologic mydriasis

• To evaluate the safety of Nyxol

• To evaluate the effect of Lumify® to suppress conjunctival hyperemia (redness) potentially associated with administration of Nyxol

Condition or Disease	Intervention/Treatment	Phase
Mydriasis; Dilation	Drug: Phentolamine Mesylate Ophthalmic Solution 1%; Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)	Phase 2

Detailed Description

Randomized, 2-arm cross-over, double-masked Phase 2b study in approximately 32 healthy subjects, evaluating safety and efficacy of Nyxol in subjects with pharmacologically induced mydriasis.

At the first visit subjects will be screened for study eligibility.

After screening, eligible subjects will be randomized 1:1 to one of the two treatment sequences:

Treatment sequence 1: Placebo (Visit 1), Nyxol (Visit 2).

Treatment sequence 2: Nyxol (Visit 1), Placebo (Visit 2).

Randomization will be stratified by mydriatic agent (2.5% phenylephrine or 1% tropicamide). Approximately one half of the randomized subjects will receive 2.5% phenylephrine and one half will receive 1% tropicamide. Subjects will receive their mydriatic agent 1 hour before treatment. Each subject will receive the same mydriatic agent throughout the study.

At each visit, pupil diameter (PD), accommodation, near and distance visual acuity (VA) and redness in each eye will be measured before (-1 hour/baseline) and 1 hour after (maximum/0 minutes) the mydriatic agent instillation in each eye (i.e., right before the study treatment is administered), and at 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after treatment dosing.

As needed, two hours post treatment, subjects may request the administration of Lumify® in the non-study eye.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Parallel AssignmentParallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Cross-Over, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution to Reverse Pharmacologically Induced Mydriasis in Normal Healthy Subjects
• Actual Study Start Date: Aug 13, 2019
• Actual Primary Completion Date: Sep 17, 2019
• Actual Study Completion Date: Sep 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phentolamine Mesylate Ophthalmic Solution 1% 1 drop in each eye, 1 hour post medically-induced mydriasis	Drug: Phentolamine Mesylate Ophthalmic Solution 1%; 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol® Nyxol
Placebo Comparator: Phentolamine Mesylate Ophthalmic Solution Vehicle 1 drop in each eye, 1 hour post medically-induced mydriasis	Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo); Topical Sterile Ophthalmic Solution

Outcome Measures

Primary Outcome Measures

1. Pupil Diameter (Change From Max) [2 hours]

   Change in pharmacologically-induced mydriatic (maximum) pupil diameter at 2 hours post-treatment in the study eye.

Secondary Outcome Measures

1. Pupil Diameter (Change From Max) [30 min, 1 hours, 4 hours, 6 hours]

   Change in pharmacologically-induced mydriatic (maximum) pupil diameter at remaining timepoints (30 min, 1 hours, 4 hours, 6 hours)

2. Pupil Diameter Return to Baseline [0 min, 1 hour, 2 hours, 4 hours, 6 hours]

   Percent of Subjects Achieving Pupil Diameter No More Than 0.5 mm Above Baseline by Time Point with either phenylephrine or tropicamide

3. Accommodation Measured by the Near Point Rule (Diopters) (Change From Baseline), Percent With Unchanged Accommodation [0 min, 2 hours, 4 hours]

   Change from baseline (-1 hour) in accommodation at each time point (0 min, 2 hours, 4 hours) with Tropicamide and Phenylephrine Worsening of accommodation is defined as an amplitude decrease of greater than 1 diopter compared to baseline

4. Conjunctival Hyperemia (Eye Redness) Assessed Visually With the Brien Holden Vision Institute (Formerly Corneal and Contact Lens Research Unit, or CCLRU) Bulbar Redness Scale (0-3) [0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours]

   Conjunctival hyperemia at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours), for study eye; in all subjects. Scale 0-3 (None, Mild, Moderate, Severe)

5. Best Corrected Distance Visual Acuity (BCDVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Light Box Chart (Letters) at 4 Meters (Change From Baseline) [0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours]

   Change from baseline (-1 hour) in Best Corrected Distance Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye

6. Distance-Corrected Near Visual Acuity (DCNVA) Measured by Standard Reading Card (Original Series Sloan Letter ETDRS Card at 16 Inches, LogMAR Units) (Change From Baseline) [0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours]

   Change from baseline (-1 hour) in Distance Corrected Near Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Males or females ≥ 18 and ≤ 45 years of age with brown irides (irises) only

2. Otherwise healthy and well controlled subjects

3. Able to comply with all protocol mandated procedures and to attend all scheduled office visits

4. Willing to give written informed consent to participate in this study

Exclusion Criteria

1. Clinically significant ocular disease as deemed by the Investigator (e.g., cataract, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) that might interfere with the study

2. Unwilling or unable to discontinue use of contact lenses during treatment visits

3. Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening

4. Ocular medication of any kind within 30 days of screening, with the exception of a) lid scrubs (which may have been used prior to, but not after screening) or b) lubricating drops for dry eye (preservative-free artificial tears), which may be used in between the study treatment days

5. Recent or current evidence of ocular infection or inflammation. Current evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes simplex or herpes zoster keratitis at screening

6. History of diabetic retinopathy

7. Closed or very narrow angles that in the Investigator's opinion are potentially occludable if the subject's pupil is dilated

8. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris (e.g., irregularly shaped pupil, neurogenic pupil disorder, iris atrophy, iridotomy)

9. Known allergy or contraindication to any component of the mydriatic agents or the vehicle formulation

10. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists (e.g., chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure (BP) or heart rate (HR); second- or third-degree heart blockage or Congestive Heart Failure (CHF); severe diabetes)

11. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine or cardiovascular disorders) that might interfere with the study

12. Initiation of treatment with or any changes to the current dosage, drug or regimen of any topical or systemic adrenergic or cholinergic drugs up to 7 days prior to screening, or during the study

13. Participation in any investigational study within 30 days prior to screening

14. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Acceptable methods include the use of at least one of the following: intrauterine device (IUD), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. An adult woman is considered to be of childbearing potential unless she is 1 year postmenopausal or 3 months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at Visit 1/Screening and Visit 2 examinations and must intend to not become pregnant during the study

15. Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit. HR may be repeated only once if outside the normal range following at least a 5-minute rest period in the sitting position

16. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg at the Screening Visit. BP may be repeated only once if outside the specified range following at least a 5-minute rest period in the sitting position

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kannar Eye Care	Pittsburg	Kansas	United States	66762
2	Kentucky Eye Institute	Lexington	Kentucky	United States	40517
3	Athens Eye Care	Athens	Ohio	United States	45701
4	West Bay Eye Associates	Warwick	Rhode Island	United States	02888

Sponsors and Collaborators

• Ocuphire Pharma, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 24, 2019
• Statistical Analysis Plan - Oct 10, 2019

More Information

Publications

None provided.

• Responsible Party: Ocuphire Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04024891
• Other Study ID Numbers: OPI-NYXRM-201 (MIRA-1)
• First Posted: Jul 18, 2019
• Last Update Posted: Aug 15, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ocuphire Pharma, Inc.: Nyxol; Pharmacologically Induced Mydriasis; Dilation
• Additional relevant MeSH terms: Mydriasis; Dilatation, Pathologic; Phentolamine; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Pre-assignment Detail	This is a crossover design study, so all 32 enrolled subjects were included in both treatment groups.

Arm/Group Title	PMOS 1% First, Then PMOS Vehicle	PMOS Vehicle First, Then PMOS 1%
Arm/Group Description	Participant received Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist at Visit 1. Then, after one week, they received Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 2. 1 drop in each eye, 1 hour post medically-induced mydriasis at both visits.	Participants received Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution at Visit 1. Then, after one week, they received Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist at Visit 2. 1 drop in each eye, 1 hour post medically-induced mydriasis for both visits.
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	15
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	PMOS 1% First, Then PMOS Vehicle	PMOS Vehicle First, Then PMOS 1%	Total
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution	Total of all reporting groups
Overall Participants	15	16	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (8.54)	27.6 (8.18)	28.0 (8.23)
Sex: Female, Male (Count of Participants)
Female	10 66.7%	9 56.3%	19 61.3%
Male	5 33.3%	7 43.8%	12 38.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Iris Color (Count of Participants)
Brown	15 100%	16 100%	31 100%
Non-Brown	0 0%	0 0%	0 0%
Mydriatic Agent Recieved (Count of Participants)
Phenylephrine	7 46.7%	8 50%	15 48.4%
Tropicamide	8 53.3%	8 50%	16 51.6%
Baseline Pupil Diameter (Study Eye) (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	4.5 (0.79)	4.5 (0.80)	4.5 (0.78)
Maximum Dilated Pupil Diameter (Study Eye) (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	7.2 (1.04)	7.3 (1.04)	7.3 (1.02)

Outcome Measures

1. Primary Outcome

Title	Pupil Diameter (Change From Max)
Description	Change in pharmacologically-induced mydriatic (maximum) pupil diameter at 2 hours post-treatment in the study eye.
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

Crossover design study

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
Least Squares Mean (Standard Error) [mm]	-1.69 (0.117)	-0.69 (0.117)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phentolamine Mesylate Ophthalmic Solution 1%, Phentolamine Mesylate Ophthalmic Solution Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.3 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Pupil Diameter (Change From Max)
Description	Change in pharmacologically-induced mydriatic (maximum) pupil diameter at remaining timepoints (30 min, 1 hours, 4 hours, 6 hours)
Time Frame	30 min, 1 hours, 4 hours, 6 hours

Outcome Measure Data

Analysis Population Description

Crossover design trial

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
30 minutes	-0.06 (0.039)	-0.13 (0.0034)
1 hour	-0.77 (0.072)	-0.29 (0.072)
4 hours	-2.83 (0.145)	-1.69 (0.146)
6 hours	-3.24 (0.132)	-2.54 (0.133)

3. Secondary Outcome

Title	Pupil Diameter Return to Baseline
Description	Percent of Subjects Achieving Pupil Diameter No More Than 0.5 mm Above Baseline by Time Point with either phenylephrine or tropicamide
Time Frame	0 min, 1 hour, 2 hours, 4 hours, 6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
0 min	3 20%	2 12.5%
1 hour	3 20%	6 37.5%
2 hour	6 40%	11 68.8%
4 hour	12 80%	24 150%
6 hour	28 186.7%	31 193.8%

4. Secondary Outcome

Title	Accommodation Measured by the Near Point Rule (Diopters) (Change From Baseline), Percent With Unchanged Accommodation
Description	Change from baseline (-1 hour) in accommodation at each time point (0 min, 2 hours, 4 hours) with Tropicamide and Phenylephrine Worsening of accommodation is defined as an amplitude decrease of greater than 1 diopter compared to baseline
Time Frame	0 min, 2 hours, 4 hours

Outcome Measure Data

Analysis Population Description

Crossover Design Trial

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
Unchanged Accommodation	3 20%	2 12.5%
Changed Accommodation (≥1 D)	13 86.7%	14 87.5%
Unchanged Accommodation	7 46.7%	3 18.8%
Changed Accommodation (≥1 D)	9 60%	13 81.3%
Unchanged Accommodation	11 73.3%	7 43.8%
Changed Accommodation (≥1 D)	5 33.3%	9 56.3%
Unchanged Accommodation	10 66.7%	11 68.8%
Changed Accommodation (≥1 D)	5 33.3%	4 25%
Unchanged Accommodation	11 73.3%	13 81.3%
Changed Accommodation (≥1 D)	4 26.7%	2 12.5%
Unchanged Accommodation	12 80%	13 81.3%
Changed Accommodation (≥1 D)	3 20%	2 12.5%

5. Secondary Outcome

Title	Conjunctival Hyperemia (Eye Redness) Assessed Visually With the Brien Holden Vision Institute (Formerly Corneal and Contact Lens Research Unit, or CCLRU) Bulbar Redness Scale (0-3)
Description	Conjunctival hyperemia at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours), for study eye; in all subjects. Scale 0-3 (None, Mild, Moderate, Severe)
Time Frame	0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours

Outcome Measure Data

Analysis Population Description

All randomized participants who recieved the medication.

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	32
Baseline (-1 hr)	0.45 (0.568)	0.35 (0.486)
0 min	0.23 (0.497)	0.29 (0.461)
30 min	1.52 (0.677)	0.42 (0.502)
1 hr	1.55 (0.675)	0.45 (0.568)
2 hr	1.42 (0.620)	0.45 (0.568)
4 hr	1.10 (0.539)	0.42 (0.564)
6 hr	0.81 (0.654)	0.35 (0.486)

6. Secondary Outcome

Title	Best Corrected Distance Visual Acuity (BCDVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Light Box Chart (Letters) at 4 Meters (Change From Baseline)
Description	Change from baseline (-1 hour) in Best Corrected Distance Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye
Time Frame	0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
0 mins	-0.45 (2.142)	-0.81 (2.182)
30 mins	-0.55 (2.188)	-0.55 (1.690)
1 hour	0.29 (1.774)	-0.10 (2.797)
2 hours	0.65 (2.727)	0.16 (2.162)
4 hours	1.06 (2.205)	0.10 (2.119)
6 hours	0.45 (3.982)	0.90 (2.399)

7. Secondary Outcome

Title	Distance-Corrected Near Visual Acuity (DCNVA) Measured by Standard Reading Card (Original Series Sloan Letter ETDRS Card at 16 Inches, LogMAR Units) (Change From Baseline)
Description	Change from baseline (-1 hour) in Distance Corrected Near Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye
Time Frame	0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%	Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
Measure Participants	31	31
0 mins	0.14 (0.194)	0.13 (0.216)
30 mins	0.09 (0.156)	0.09 (0.217)
1 hour	0.05 (0.146)	0.07 (0.142)
2 hours	0.03 (0.113)	0.00 (0.087)
4 hours	0.00 (0.075)	0.01 (0.079)
6 hours	-0.02 (0.083)	0.00 (0.055)

Adverse Events

Time Frame	2 weeks.
Adverse Event Reporting Description	All AEs/adverse reactions occurring during the study (ie, once the subject had signed the informed consent) were documented on the CRF, regardless of the assumption of causal relationship. All TEAEs/adverse reactions were documented from the time the subject received the first dose of study medication until the subject's participation in the study had completed.
Arm/Group Title	Phentolamine Mesylate Ophthalmic Solution 1%		Phentolamine Mesylate Ophthalmic Solution Vehicle
Arm/Group Description	1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution 1%: 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist		1 drop in each eye, 1 hour post medically-induced mydriasis Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution
All Cause Mortality
	Phentolamine Mesylate Ophthalmic Solution 1%		Phentolamine Mesylate Ophthalmic Solution Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Serious Adverse Events
	Phentolamine Mesylate Ophthalmic Solution 1%		Phentolamine Mesylate Ophthalmic Solution Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Phentolamine Mesylate Ophthalmic Solution 1%		Phentolamine Mesylate Ophthalmic Solution Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/31 (35.5%)		1/32 (3.1%)
Eye disorders
Conjunctival Hyperemia	11/31 (35.5%)		0/32 (0%)
Gastrointestinal disorders
Abdominal Pain, Upper	0/31 (0%)		1/32 (3.1%)
Nausea	0/31 (0%)		1/32 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.