| Eligibility |
Inclusion Criteria:
1. Participants must provide written, signed and dated informed consent to participate in
the study in accordance with the International Council for Harmonisation (ICH) Good
Clinical Practice (GCP) Guideline E6(R1) and applicable regulations, before completing
any study-related procedures.
2. Participants must be aged from 18 through 90 at the time of consent. This inclusion
criterion will only be assessed at the screening visit.
3. Participants must have ocular hypertension (OHT) or stable early primary open-angle
glaucoma (POAG) in both eyes with acceptable Humphrey visual fields (HVF). Early POAG
for this protocol is defined as healthy appearing anterior chamber angles (Shaffer
classification system grade 3 or 4) and focal and/or generalized thinning of the optic
disc rim characteristic of glaucomatous disease. An acceptable HVF must have been
performed within approximately one year of screening, have a false-positive rate of 25
percent (%) maximum, false-negative rate of 25% maximum, and fixation loss rate of 33%
maximum, and mean deviation of no worse than -6.00 decibels (dB).
4. On Day -1, participants must have a mean IOP of greater than or equal to (>=) 24
millimeter of mercury (mmHg) at 8:00 AM and a mean IOP of >= 22 mmHg at 10:00 AM in at
least 1 eye, with an IOP difference of less than (<) 4 mmHg between eyes at both of
these time points. If only 1 eye meets this criterion, then it will be the designated
study eye for pharmacodynamic analysis; this eye will also be used for dosing in
Cohort A single-dose treatment period (SDTP).
5. Participants must have a best-corrected visual acuity (BCVA) in both eyes of 65
letters on the Early Treatment Diabetic Retinopathy Study chart (Snellen equivalent
approximately [~] 20/60) or better at the screening and baseline assessments.
6. Participants must be males or females who are non-pregnant and non-lactating at
screening (negative serum beta-human chorionic gonadotropin [beta-hCG]); if sexually
active during the study, they must agree to comply with the applicable contraceptive
requirements throughout the study period and for 60 days following the last dose of
investigational product.
7. Participants must have a satisfactory medical assessment with no clinically
significant or relevant abnormalities as determined by medical history, physical
examination, and clinical and laboratory evaluation (hematology, biochemistry,
urinalysis) as assessed by the investigator.
8. Participants must understand and be able, willing, and likely to fully comply with
study procedures and restrictions.
9. Participants must be non-smokers or have had stable use of tobacco or
nicotine-containing products for a 3-month period before signing the informed consent
form (ICF).
10. Participants who drink alcohol must have had stable use of alcohol for a 3-month
period before signing the ICF.
Exclusion Criteria:
1. Participant has an anatomically narrow angle, synechiae or evidence of prior
inflammation, angle closure glaucoma, normal tension glaucoma, pseudoexfoliation
syndrome or pigmentary dispersion syndrome with or without glaucoma, or secondary
glaucoma.
2. Participant has corneal endothelial cell counts of less than 2000 cells per
millimeter^2 (measured by noncontact specular microscopy) at the screening or baseline
assessments.
3. Participant has central corneal thickness less than 500 micrometer (mcm) or greater
than 620 mcm at the screening or baseline assessments.
4. Participant has IOP greater than 32 mmHg in either eye before randomization.
5. Participant has used topical ocular hypotensive medications as follows: prostaglandin
analogs, beta-adrenoceptor antagonists, alpha-adrenergic agonists, or
epinephrine-related medications within 4 weeks before the first dose of
investigational product; or pilocarpine or carbonic anhydrase inhibitors within 7 days
before the first dose of investigational product.
6. Participant has a history of angle closure, ocular surgery, microinvasive glaucoma
surgery device insertion, or laser surgery, except for the following procedures, which
are allowed: uncomplicated cataract surgery, laser peripheral iridotomy with resultant
angle of Shaffer grade 3 or 4, and postcataract neodymium-doped
yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy. Cataract surgery and
other procedures must have occurred a minimum of 3 months before randomization.
7. Participant has a history of significant ocular trauma or ocular disease including but
not limited to moderate to severe dry eye disease that requires chronic treatment or
punctal plugs.
8. Participant has evidence of ocular infection, inflammation, degeneration, or dystrophy
at the screening or baseline assessments, including but not limited to moderate to
severe blepharitis (mild blepharitis is allowed), conjunctivitis (allergic or
infectious), corneal dystrophy (epithelial, stromal, or endothelial), corneal haze of
grade 1 or greater based on the Hwang Grading Scale of Corneal Haze, corneal
opacities, keratitis, uveitis, or vitritis.
9. Participant has retinal disease including but not limited to: moderate or severe
non-proliferative diabetic retinopathy (NPDR) (early NPDR is allowed), proliferative
diabetic retinopathy, intermediate or advanced dry age-related macular degeneration
(AMD) (early dry AMD is allowed), all geographic atrophy, or all wet AMD.
10. Participant has any non-glaucomatous optic neuropathy or other significant
non-glaucomatous ocular disease that is likely to affect visual function.
11. Participant has any corneal or ocular surface pathology in either eye that prevents
proper IOP measurement, pachymetry, or other study data collection procedures.
12. Participant has had changes to their existing prescription medication regimen for
chronic disease, including those medicines that affect IOP, within 14 days or 5
half-lives before screening, whichever is longer.
13. Participant has started any new prescription drug medication for chronic disease,
including those medicines that affect IOP, within 14 days or 5 half-lives before
screening, whichever is longer.
14. Participant has a history of corticosteroid use within 3 months before randomization,
except for non-periocular dermatologic use, which is allowed.
15. Participant has used belladonna alkaloids (scopolamine, hyoscamine, atropine) within 7
days prior to randomization, cannabinoids or opioids within 28 days before
randomization, or B-type natriuretic peptides within the past year before
randomization; or a participant has an anticipated need for any of the aforementioned
drugs/drug categories during the study.
16. Participant has used amantadine within 28 days before randomization.
17. Participant is unable to discontinue contact lens use during and for 60 minutes
following instillation of study medication, during ophthalmologic examinations, and
during study visits.
18. Participant has a current or relevant history of any physical, medical, mental, or
psychiatric illness, disorder, or condition that may require treatment during the
study and/or that may interfere with the participant complying with the study rules
and procedures or completing the study.
19. Participant has any condition that presents undue risk from use of the investigational
product, assessment tools, or procedures.
20. Participant is a woman who is pregnant (positive serum beta-hCG pregnancy test at the
time of screening), lactating, or less than 90 days post-partum at randomization.
21. Participant has donated blood within 60 days before first dose of investigational
product.
22. Participant has donated plasma within 28 days before first dose of investigational
product.
23. Participant has used another investigational product within 30 days before the first
dose of investigational product or is actively enrolled in a drug or vaccine clinical
study.
24. Participant has a positive human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C virus (HCV) antibodies screen.
25. Participant has a positive drugs of abuse screen or alcohol breathalyzer test.
26. Participant has been previously enrolled in this study.
27. Participant has known hypersensitivity or allergy to any of the ingredients of the
investigational product.
28. Participant consumes more than 21 units of alcohol per week or is unable to refrain
from alcohol consumption within 48 hours before a scheduled visit. (1 alcohol unit=1
beer or 1 wine [5 ounce per 150 milliliter] or 1 liquor [1.5 ounce per 40 milliliter]
or 0.75 ounce alcohol.)
29. Participant is unable to refrain from tobacco or any products containing nicotine
within 8 hours before a scheduled visit.
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