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CompletedNCT04620213Updated Oct 30, 2026Results posted

Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis

A Phase 3 interventional study of Phentolamine Ophthalmic Solution 0.75% and Phentolamine Ophthalmic Solution Vehicle (Placebo) in Mydriasis and Dilation, sponsored by Opus Genetics, Inc. Completed at 12 sites in United States. Open to participants aged 12 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-30.

Sponsored by Opus Genetics, Inc · Phase 3, Interventional, and Treatment

Updated Oct 30, 2026Sponsor changedGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
185
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study summary

The objectives of this study are:

  • To evaluate the efficacy of Nyxol to expedite the reversal of pharmacologically-induced mydriasis across multiple mydriatic agents with an emphasis on phenylephrine
  • To evaluate the efficacy of Nyxol to return subjects to baseline accommodation after worsening (with cycloplegic agents tropicamide and Paremyd)
  • To evaluate the safety of Nyxol
  • To evaluate any additional benefits of the reversal of pharmacologically-induced mydriasis
Read the detailed description

A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 168 randomized subjects (160 completed), evaluating the safety and efficacy of Nyxol in subjects with pharmacologically-induced mydriasis.

Following the successful completion of screening, each subject will be stratified by eye color and then simultaneously be randomized to mydriatic agent (unmasked) and treatment (masked).

Treatment randomization will be 1:1, Nyxol or placebo (vehicle).

Stratification by iris color will be 1:1, light or dark irides.

The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd). That is, approximately 60% of the randomized subjects will receive one drop of 2.5% phenylephrine 1 hour before treatment (96 completed subjects), approximately 20% will receive one drop of 1% tropicamide 1 hour before treatment (32 completed subjects), and approximately 20% will receive Paremyd 1 hour before treatment (32 completed subjects).

At the treatment visit, subjects who have been randomized and stratified by iris color (1:1 [light/dark]) will receive one of three approved mydriatic agents approximately 1 hour prior to receiving study treatment. Measurements will be measured before (-1 hour /baseline) and 60 minutes after (maximum/0 minutes) the mydriatic agent instillation in each eye (i.e. right before the study treatment is administered), and at 30 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, and 6 hours after treatment dosing. Measurements will include pupil diameter (PD), distance and near visual acuity (VA), accommodation, and redness in each eye.

At the Follow-Up Visit, which is 1 day after Visit 1, measurements will again be recorded 24 hours after treatment dosing.

02

Conditions studied

  • Mydriasis
  • Dilation

Keywords

  • Nyxol
  • Pharmacologically Induced Mydriasis
  • Dilation
03

In context

Mydriasis

37 studies on the registry are indexed under Mydriasis; 4 are open to participants now.

This study's enrollment of 185 is above the median of 61 across 35 interventional studies indexed under Mydriasis.

Browse Mydriasis studies →

Lead sponsor

Opus Genetics, Inc is the lead sponsor of 17 studies on the registry; 4 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Males or females ≥ 12 years of age
  2. Otherwise healthy and well controlled subjects

Exclusion criteria

Exclusion Criteria:

Ophthalmic (in either eye):

  1. ocular disease as deemed by the Investigator that might interfere with the study
  2. Unwilling or unable to discontinue use of contact lenses at screening until study completion
  3. Unwilling or unable to suspend use of topical medication at screening until study completion
  4. Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening
  5. Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening
  6. Recent or current evidence of ocular infection or inflammation in either eye
  7. History of diabetic retinopathy or diabetic macular edema
  8. Closed or very narrow angles that in the Investigator's opinion are potentially occludable if the subject's pupil is dilated
  9. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris
  10. Known allergy or to any component of the mydriatic agents or the vehicle formulation
  11. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal

Systemic:

  1. Known or contraindication to α- and/or β adrenoceptor antagonists.
  2. Clinically significant systemic disease that might interfere with the study
  3. Initiation of treatment with or any changes to the current dosage, drug or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to screening, or during the study
  4. Participation in any study within 30 days prior to screening
  5. Females of who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of
  6. Resting HR outside the normal range (50-110 beats per minute)
  7. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
185 participants (actual)

Study arms

  • Experimental
    Phentolamine Ophthalmic Solution 0.75%

    2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis

    Drug: Phentolamine Ophthalmic Solution 0.75%

  • Placebo comparator
    Phentolamine Ophthalmic Solution Vehicle

    2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis

    Other: Phentolamine Ophthalmic Solution Vehicle (Placebo)

Interventions

  • DrugPhentolamine Ophthalmic Solution 0.75%

    0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist

    Also known as: Nyxol, Nyxol®

  • OtherPhentolamine Ophthalmic Solution Vehicle (Placebo)

    Topical sterile ophthalmic solution

06

What researchers measure

Primary outcomes

  1. Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline

    Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter

    Time frame: 90 minutes

Secondary outcomes

  1. Percent of Subjects' Study Eyes Pupil Diameter Returning to Baseline

    Percentage of subjects' study eyesreturning to less than or equal to 0.2 mm from baseline pupil diameter

    Time frame: up to 24 hours

  2. Pupil Diameter (Change From Max)

    Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)

    Time frame: up to 24 hours

  3. Percent of Subjects With Unchanged Accommodation From Baseline

    Percentage of subjects with unchanged accommodation from baseline (-1 hour)

    Time frame: up to 6 hours

07

Results

Posted Aug 14, 2023

Participant flow

Participant flow — Overall Study
MilestonePhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
Started9491
Completed9491
Not completed00

Outcome measures

PrimaryPercent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline

Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter

Time frame:
90 minutes
Reported as:
Count of participants · Participants
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
ParticipantsPhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline466
SecondaryPercent of Subjects' Study Eyes Pupil Diameter Returning to Baseline

Percentage of subjects' study eyesreturning to less than or equal to 0.2 mm from baseline pupil diameter

Time frame:
up to 24 hours
Reported as:
Count of participants · Participants
Percent of Subjects' Study Eyes Pupil Diameter Returning to Baseline
ParticipantsPhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
30 minutes13
60 minutes262
90 minutes466
2 hours5510
3 hours7516
4 hours7727
6 Hours8541
24 Hours8660
SecondaryPupil Diameter (Change From Max)

Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)

Time frame:
up to 24 hours
Reported as:
Mean · millimeters
Pupil Diameter (Change From Max)
millimetersPhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
Baseline (-1 Hour)5.085 ± 0.92955.177 ± 0.9678
0 minutes7.207 ± 1.0247.197 ± 1.1717
30 minutes0.025 ± 0.47800.075 ± 0.4266
60 minutes-1.308 ± 0.8705-0.122 ± 0.4055
90 minutes-2.192 ± 1.0117-0.329 ± 0.4653
2 hours-2.429 ± 0.9837-0.518 ± 0.5930
3 hours-2.828 ± 0.9817-0.806 ± 0.6253
4 hours-2.991 ± 1.0793-1.159 ± 0.8223
6 hours-3.338 ± 1.0797-1.634 ± 1.0595
24 Hours-3.375 ± 1.2302-2.173 ± 1.3868
SecondaryPercent of Subjects With Unchanged Accommodation From Baseline

Percentage of subjects with unchanged accommodation from baseline (-1 hour)

Time frame:
up to 6 hours
Reported as:
Count of participants · Participants
Percent of Subjects With Unchanged Accommodation From Baseline
ParticipantsPhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
Phenylephrine, 0 minutes — Unchanged from Baseline3037
Phenylephrine, 0 minutes — Changed from Baseline2618
Phenylephrine, 60 minutes — Unchanged from Baseline2939
Phenylephrine, 60 minutes — Changed from Baseline2716
Phenylephrine, 90 minutes — Unchanged from Baseline3840
Phenylephrine, 90 minutes — Changed from Baseline1815
Phenylephrine, 2 hours — Unchanged from Baseline4042
Phenylephrine, 2 hours — Changed from Baseline1613
Phenylephrine, 3 hours — Unchanged from Baseline3845
Phenylephrine, 3 hours — Changed from Baseline1810
Phenylephrine, 4 hours — Unchanged from Baseline3942
Phenylephrine, 4 hours — Changed from Baseline1713
Phenylephrine, 6 hours — Unchanged from Baseline4348
Phenylephrine, 6 hours — Changed from Baseline137
Tropicamide, 0 Minutes — Unchanged from Baseline22
Tropicamide, 0 Minutes — Changed from Baseline1716
Tropicamide, 60 Minutes — Unchanged from Baseline65
Tropicamide, 60 Minutes — Changed from Baseline1313
Tropicamide, 90 Minutes — Unchanged from Baseline105
Tropicamide, 90 Minutes — Changed from Baseline913
Tropicamide, 2 Hours — Unchanged from Baseline126
Tropicamide, 2 Hours — Changed from Baseline712
Tropicamide, 3 Hours — Unchanged from Baseline138
Tropicamide, 3 Hours — Changed from Baseline610
Tropicamide, 4 Hours — Unchanged from Baseline1410
Tropicamide, 4 Hours — Changed from Baseline58
Tropicamide, 6 Hours — Unchanged from Baseline1412
Tropicamide, 6 Hours — Changed from Baseline56
Paremyd, 0 Minutes — Unchanged from Baseline23
Paremyd, 0 Minutes — Changed from Baseline1715
Paremyd, 60 Minutes — Unchanged from Baseline66
Paremyd, 60 Minutes — Changed from Baseline1312
Paremyd, 90 Minutes — Unchanged from Baseline77
Paremyd, 90 Minutes — Changed from Baseline1211
Paremyd, 2 Hours — Unchanged from Baseline97
Paremyd, 2 Hours — Changed from Baseline1011
Paremyd, 3 Hours — Unchanged from Baseline1110
Paremyd, 3 Hours — Changed from Baseline88
Paremyd, 4 Hours — Unchanged from Baseline1411
Paremyd, 4 Hours — Changed from Baseline57
Paremyd, 6 Hours — Unchanged from Baseline1411
Paremyd, 6 Hours — Changed from Baseline57
Tropicamide or Paremyd, 0 Minutes — Unchanged from Baseline45
Tropicamide or Paremyd, 0 Minutes — Changed from Baseline3431
Tropicamide or Paremyd, 60 Minutes — Unchanged from Baseline1211
Tropicamide or Paremyd, 60 Minutes — Changed from Baseline2625
Tropicamide or Paremyd, 90 Minutes — Unchanged from Baseline1712
Tropicamide or Paremyd, 90 Minutes — Changed from Baseline2124
Tropicamide or Paremyd, 2 Hours — Unchanged from Baseline2113
Tropicamide or Paremyd, 2 Hours — Changed from Baseline1723
Tropicamide or Paremyd, 3 Hours — Unchanged from Baseline2418
Tropicamide or Paremyd, 3 Hours — Changed from Baseline1418
Tropicamide or Paremyd, 4 Hours — Unchanged from Baseline2821
Tropicamide or Paremyd, 4 Hours — Changed from Baseline1015
Tropicamide or Paremyd, 6 Hours — Unchanged from Baseline2823
Tropicamide or Paremyd, 6 Hours — Changed from Baseline1013

Adverse events

Collected over 2 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Phentolamine Ophthalmic Solution 0.75%0/94 (0%)0/94 (0%)48/94 (51.1%)
Phentolamine Ophthalmic Solution Vehicle0/91 (0%)0/91 (0%)8/91 (8.8%)
Most frequent other events
Most frequent other events
EventPhentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution Vehicle
Instillation site discomfortGeneral disorders36/948/91
Conjunctival HyperaemiaEye disorders12/940/91

Baseline characteristics

Age, Continuous
Age, Continuous(years)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Mean33.9 ± 14.0432.8 ± 13.5533.4 ± 13.77
Sex: Female, Male
Sex: Female, Male(Participants)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Female5855113
Male363672
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
White7074144
American Indian or Alaska Native112
Native Hawaiian or Other Pacific Islander101
Black or African American171633
Asian639
Irides Type: Light, Dark
Irides Type: Light, Dark(Participants)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Light454590
Dark494695
Mydriatic Agent
Mydriatic Agent(Participants)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Phenylephrine5655111
Tropicamide191837
Paremyd191837
Baseline Pupil Diameter (Study Eye)
Baseline Pupil Diameter (Study Eye)(mm)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Mean5.085 ± 0.92955.177 ± 0.96785.130 ± 0.9471
Baseline Accomodation (Study Eye)
Baseline Accomodation (Study Eye)(D)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Mean10.47 ± 20.3738.25 ± 5.2309.38 ± 14.980
Baseline BCDVA (Study Eye)
Baseline BCDVA (Study Eye)(Letters)Phentolamine Ophthalmic Solution 0.75%Phentolamine Ophthalmic Solution VehicleTotal
Mean57.0 ± 4.1058.6 ± 4.4957.8 ± 4.36

2 further baseline measures are reported on the registry.

08

Study locations

12 sites
  • Clinical Site 11
    Newport Beach, California 92663, United States
  • Clinical Site 10
    San Diego, California 92123, United States
  • Clinical Site 9
    Longwood, Florida 32779, United States
  • Clinical Site 6
    Orlando, Florida 32751, United States
  • Clinical Site 2
    Roswell, Georgia 30075, United States
  • Clinical Site 7
    Pittsburg, Kansas 66762, United States
  • Clinical Site 3
    Shawnee Mission, Kansas 66203, United States
  • Clinical Site 5
    Athens, Ohio 45701, United States
  • Clinical Site 12
    Cincinnati, Ohio 45242, United States
  • Clinical Site 1
    Cleveland, Ohio 44195, United States
  • Clinical Site 8
    Warwick, Rhode Island 02888, United States
  • Clinical Site 4
    Memphis, Tennessee 38119, United States
09

References and documents

Publications

  • Pepose JS, Foster S, Pearson C, Brigell M, Charizanis K. Reversal of Pharmacologic Mydriasis in Pediatric Subjects with Ryzumvi (0.75% Phentolamine Ophthalmic Solution): A Post-Hoc Pooled Analysis from Three Randomized, Placebo-Controlled Phase 3 Trials. Clin Ophthalmol. 2026 Feb 20;20:563499. doi: 10.2147/OPTH.S563499. eCollection 2026. PubMed 41743463 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Nov 2020 to primary completion in Dec 2020, 1 month.

Results were first posted in Aug 2023, 2 years 7 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 2, 2020
First posted
Nov 6, 2020
StartActual
Nov 18, 2020
Primary completionActual
Dec 23, 2020
CompletionActual
Mar 15, 2021
Results first posted
Aug 14, 2023
Last update
Oct 30, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Publications
1 publication citing this study linked from PubMed, e.g. PubMed 41743463 ↗
Oct 30, 2026
Sponsor
Ocuphire Pharma, Inc.→Opus Genetics, Inc
Oct 30, 2026
Show all 1 update
  1. Oct 30, 2026
    Publications 1 publication citing this study linked from PubMed, e.g. PubMed 41743463 ↗
    Sponsor Ocuphire Pharma, Inc.→Opus Genetics, Inc
    + 3 other changes: identifiers, site details and index terms

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT04620213
Lead sponsor
Opus Genetics, Inc
Responsible party
Sponsor
First posted
Nov 6, 2020
Start date
Nov 18, 2020
Primary completion
Dec 23, 2020
Completion
Mar 15, 2021
Results posted
Aug 14, 2023
Last update
Oct 30, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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