MydriasisPhase 3NCT04620213
Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis
A Phase 3 study testing Phentolamine Ophthalmic Solution 0.75% in people with Mydriasis and Dilation, run by Opus Genetics, Inc at 12 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- What is being tested?
- Phentolamine Ophthalmic Solution 0.75%
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 185 participants
- Where
- 12 sitesUnited States
- Study dates
- 18 Nov 2020to 15 Mar 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Males or females ≥ 12 years of age
- Otherwise healthy and well controlled subjects
Who cannot join
- Ophthalmic (in either eye):
- Clinically significant ocular disease as deemed by the Investigator that might interfere with the study
- Unwilling or unable to discontinue use of contact lenses at screening until study completion
- Unwilling or unable to suspend use of topical medication at screening until study completion
- Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening
- Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening
Show all 20Show fewer
- Recent or current evidence of ocular infection or inflammation in either eye
- History of diabetic retinopathy or diabetic macular edema
- Closed or very narrow angles that in the Investigator's opinion are potentially occludable if the subject's pupil is dilated
- History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris
- Known allergy or contraindication to any component of the mydriatic agents or the vehicle formulation
- History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
- Systemic:
- Known hypersensitivity or contraindication to α- and/or β adrenoceptor antagonists.
- Clinically significant systemic disease that might interfere with the study
- 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
- Participation in any investigational study within 30 days prior to screening
- Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
- Resting HR outside the normal range (50-110 beats per minute)
- Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Clinical Site 5
Athens, Ohio, 45701
Clinical Site 12
Cincinnati, Ohio, 45242
Clinical Site 1
Cleveland, Ohio, 44195
Clinical Site 9
Longwood, Florida, 32779
Clinical Site 4
Memphis, Tennessee, 38119
Clinical Site 11
Newport Beach, California, 92663
Clinical Site 6
Orlando, Florida, 32751
Clinical Site 7
Pittsburg, Kansas, 66762
Clinical Site 2
Roswell, Georgia, 30075
Clinical Site 10
San Diego, California, 92123
Clinical Site 3
Shawnee Mission, Kansas, 66203
Clinical Site 8
Warwick, Rhode Island, 02888
About this study
Official title: Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects
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.
- Being tested
- Phentolamine Ophthalmic Solution 0.75%, Phentolamine Ophthalmic Solution Vehicle (Placebo)
- Keywords
- Nyxol, Pharmacologically Induced Mydriasis, Dilation
- Medical subject headings
- Mydriasis, Dilatation, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phentolamine Ophthalmic Solution 0.75%Drug
Also called Nyxol, Nyxol®
0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
Phentolamine Ophthalmic Solution Vehicle (Placebo)Other
Topical sterile ophthalmic solution
| Study group | Role | What they receive |
|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Experimental | 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis Receives: Drug: Phentolamine Ophthalmic Solution 0.75% |
| Phentolamine Ophthalmic Solution Vehicle | Placebo comparator | 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis Receives: Other: Phentolamine Ophthalmic Solution Vehicle (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 90 minutes
Secondary outcomes (3)
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
Measured: up to 24 hours
Pupil Diameter (Change From Max)
Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)
Measured: up to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline
Percentage of subjects with unchanged accommodation from baseline (-1 hour)
Measured: up to 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start18 Nov 2020
- Primary completion23 Dec 2020
- Study completion15 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MydriasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- Opus Genetics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04620213
- Sponsor's protocol ID
- OPI-NYXRM-301 (MIRA-2)
- Status last verified
- Aug 2023
- First submitted
- 2 Nov 2020
- Last updated
- 30 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04620213
- Acronym / sponsor ID
- OPI-NYXRM-301 (MIRA-2)
- Keywords
- Nyxol, Pharmacologically Induced Mydriasis, Dilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- Opus Genetics, IncIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- 23 Dec 2020 (actual)
- Study completion
- 15 Mar 2021 (actual)
- First posted
- 6 Nov 2020 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Experimental | Drug: Phentolamine Ophthalmic Solution 0.75%2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis |
| Phentolamine Ophthalmic Solution Vehicle | Placebo comparator | Other: Phentolamine Ophthalmic Solution Vehicle (Placebo)2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Males or females ≥ 12 years of age
- Otherwise healthy and well controlled subjects
Key exclusion criteria (20 listed)
- Clinically significant ocular disease as deemed by the Investigator that might interfere with the study
- Unwilling or unable to discontinue use of contact lenses at screening until study completion
- Unwilling or unable to suspend use of topical medication at screening until study completion
- Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening
- Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phentolamine Ophthalmic Solution 0.75%Also: Nyxol, Nyxol®0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist | Drug | Phentolamine Ophthalmic Solution 0.75% |
| Phentolamine Ophthalmic Solution Vehicle (Placebo)Topical sterile ophthalmic solution | Other | Phentolamine Ophthalmic Solution Vehicle |
Primary outcome
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
Time frame: 90 minutes
Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter
3 secondary outcomes
Percent of Subjects' Study Eyes Pupil Diameter Returning to Baseline
Time frame: up to 24 hours
Pupil Diameter (Change From Max)
Time frame: up to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline
Time frame: up to 6 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41743463Pepose 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Phentolamine Ophthalmic Solution 0.75% in people with Mydriasis and Dilation, run by Opus Genetics, Inc at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline (time frame: 90 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04620213, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.