Study of SHP639 Eye Drops in Adults With High Eye Pressure or Primary Open-angle Glaucoma
Condition: Primary Open-angle Glaucoma (POAG); Ocular Hypertension
MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension
Intervention: SHP639 (n=60); Placebo Comparator (n=24)
Intervention description: Drug SHP639 is a 9-amino acid, synthetic, C-type natriuretic peptide (CNP) analog.; Drug: Vehicle Ophthalmic placebo solution of the same composition as the test product.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      Safety and tolerability of three different concentrations (0.1%, 03%, 0.6%) of the
      investigational SHP639 eye drops will be evaluated in participants with high eye pressure or
      primary open-angle glaucoma.
    

Eligibility criteria:

        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.