MydriasisPhase 3MIRA-3NCT05134974
Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis (MIRA-3)
A Phase 3 study testing Phentolamine Ophthalmic Solution 0.75% in people with Mydriasis and Dilation, run by Opus Genetics, Inc at 15 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
- 368 participants
- Where
- 15 sitesUnited States
- Study dates
- 18 Nov 2021to 29 Mar 2022
- 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
- Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits
Who cannot join
- Clinically significant ocular disease as deemed by the Investigator (eg, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) 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, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
- Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, or keratitis). Subjects must be symptom-free for at least 7 days prior to screening
Show all 13Show fewer
- Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject's pupil is dilated
- Prior participation in a study involving the use of Nyxol for the reversal of mydriasis
- Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
- Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study
- Participation in any investigational study within 30 days prior to screening
- Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit.
- Hypertension with resting diastolic blood pressure (BP)>105 mmHg or systolic BP > 160 mmHg at the Screening Visit.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Clinical Site 4
Athens, Ohio, 45701
Clinical Site 2
Bloomington, Minnesota, 55420
Clinical Site 9
Delray Beach, Florida, 33484
Clinical Site 15
Garner, North Carolina, 27529
Clinical Site 13
Lake Villa, Illinois, 60046
Clinical Site 8
Longwood, Florida, 32779
Clinical Site 3
Memphis, Tennessee, 38119
Clinical Site 6
Morrow, Georgia, 30260
Clinical Site 10
Newport Beach, California, 92663
Clinical Site 5
Pittsburg, Kansas, 66762
Clinical Site 1
Roswell, Georgia, 30009
Clinical Site 14
Shrewsbury, Pennsylvania, 17349
Clinical Site 11
Sioux Falls, South Dakota, 57101
Clinical Site 7
Warwick, Rhode Island, 02888
Clinical Site 12
Westminster, California, 92655
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
- To evaluate the systemic exposure of Nyxol on pharmacokinetic (PK) sampling
Read the detailed description
A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 330 randomized subjects, 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 2:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark rides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd).
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.
Blood sampling for Nyxol PK measurements will be conducted in a subset of approximately 30 adult subjects at approximately two select study sites.
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
- 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 VehicleDrug
Phentolamine Ophthalmic Solution Vehicle
| Study group | Role | What they receive |
|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Active comparator | 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: Drug: Phentolamine Ophthalmic Solution Vehicle |
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 (4)
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: 30 minutes to 24 hours
Pupil Diameter (Change From Max)
Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)
Measured: 30 minutes to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline
Percentage of subjects with unchanged accommodation from baseline (-1 hour)
Measured: 90 minutes to 6 Hours
Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions
Change from Baseline in best-corrected distance visual acuity (BCDVA) under normal photopic lighting without glare conditions
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study start18 Nov 2021
- Primary completion18 Mar 2022
- Study completion29 Mar 2022
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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 368 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
- NCT05134974
- Sponsor's protocol ID
- OPI-NYXRM-302 (MIRA-3)
- Acronym
- MIRA-3
- Status last verified
- Aug 2023
- First submitted
- 16 Nov 2021
- Last updated
- 30 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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
- NCT05134974
- Acronym / sponsor ID
- MIRA-3 / OPI-NYXRM-302 (MIRA-3)
- Keywords
- Nyxol, Pharmacologically Induced Mydriasis, Dilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 368 participants (actual)
- Lead sponsor
- Opus Genetics, IncIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2021 (actual)
- Primary completion
- 18 Mar 2022 (actual)
- Study completion
- 29 Mar 2022 (actual)
- First posted
- 26 Nov 2021 (actual)
- Results
- Posted 1 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
- To evaluate the systemic exposure of Nyxol on pharmacokinetic (PK) sampling
Detailed description
A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 330 randomized subjects, 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 2:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark rides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd).
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.
Blood sampling for Nyxol PK measurements will be conducted in a subset of approximately 30 adult subjects at approximately two select study sites.
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
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Active comparator | 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 | Drug: Phentolamine Ophthalmic Solution Vehicle2 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
- Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits
Key exclusion criteria (13 listed)
- Clinically significant ocular disease as deemed by the Investigator (eg, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) 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, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
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®, Nyxol0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist | Drug | Phentolamine Ophthalmic Solution 0.75% |
| Phentolamine Ophthalmic Solution VehiclePhentolamine Ophthalmic Solution Vehicle | Drug | 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
4 secondary outcomes
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
Time frame: 30 minutes to 24 hours
Pupil Diameter (Change From Max)
Time frame: 30 minutes to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline
Time frame: 90 minutes to 6 Hours
Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions
Time frame: 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.
15 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 15 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 13 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 15 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 1 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 NCT05134974, 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.