A Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7058584 Following 7 Days of Instillation of Eye Drops in Patients With Primary Open Angle Glaucoma or Ocular Hypertension

Phase 1

Completed

Interventions: Drug: 0.01% RO7058584
Drug: 1% RO7058584
Drug: Matching Placebo
Drug: 0.1% RO7058584
Drug: Latanoprost 0.005%

Brief Summary: This is a Phase I, multi-center, randomized, adaptive, investigator/patient-masked, placebo-controlled, parallel multiple-ascending dose study (Part A) with an extension including up to two selected doses from Part A and latanoprost 0.005% as active comparator (Part B).

Recruitment & Eligibility

Inclusion Criteria

18 to 90 years of age inclusive, at the time of signing the informed consent form
Confirmed diagnosis of ocular hypertension (OHT) or primary open-angle glaucoma (POAG) in both eyes as determined by the investigator at screening
Treatment-naïve participants or participants who are able to safely stop their Intraocular pressure (IOP)-lowering medication(s) prior to randomization according to the required minimum washout periods
At baseline visit, IOP ≥ 24 millimeters of mercury (mmHg) in the morning (8:00 AM ± 1h) and ≥ 22 mmHg in the afternoon (2:00 PM ± 1h) measurement in the same eye and ≤ 34 mmHg at all timepoints in both eyes
Best corrected logarithm of the minimum angle of resolution (logMAR) visual acuity score of 0.7 or better in each eye as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity test at screening
Central corneal thickness (pachymetry) measurement 450 to 620 micrometers (μm) in both eyes at screening
Cup-to-disc ratio ≤ 0.8 (both eyes) at screening
Anterior chamber angle is open and non-occludable (both eyes) as confirmed by the investigator by gonioscopy examination at screening

Exclusion Criteria

Advanced visual field defects
Other forms of glaucoma than POAG or OHT
Any abnormality preventing reliable applanation tonometry
Any clinically significant corneal scarring, haze or opacity
Uncooperativeness of the participant that restricts adequate examination of IOP, ocular fundus or anterior chamber
Any presence or history of uveitis or other history of any ocular inflammatory disease.
History or signs of penetrating ocular trauma
Risk of visual field or visual acuity worsening in either eye as a consequence of glaucoma progression or consequence of participation in the trial or any other ocular disease, according to the investigator's best judgment
History of any glaucoma surgery
History of refractive surgery
Any other intra-ocular surgery within six months of screening
Any active ocular disease requiring treatment.
Use of any listed prohibited medications
Current enrollment or past participation within the last 30 days before the screening visit in any other clinical study involving an investigational study treatment or any other type of medical research
Any participant who is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff thereof, directly involved in the conduct of the protocol

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Incidence, Severity, and Causal Relationship of Ocular and Systemic Adverse Events (AEs)	Up to 12 weeks	An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Incidence of Blood Pressure Abnormalities	Up to 12 weeks
Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration	7 days	IOP will be assessed by Goldman Applanation tonometry.
Incidence of Electrocardiogram (ECG) Findings	Up to 12 weeks
Incidence of Pulse Rate Abnormalities	Up to 12 weeks
Incidence of Abnormal Laboratory Findings	Up to 12 weeks

Secondary Outcome Measures

Name	Time	Method
Cmax of RO7058584	Up to Day 8	Cmax is the maximum observed plasma concentration.
Ctrough of RO7058584	Up to Day 8	Ctrough is the concentration at the end of a dosing interval before the next dose administration.
AUC0-24h of RO7058584	Up to Day 8	AUC0-24h is the area under the plasma concentration versus time curve (AUC) from Time 0 to 24 h post-dose.
Change From Baseline in Mean Intraocular pressure (IOP) at Matched Clock-Times After 7 Days of Study Drug Administration	7 days	IOP will be assessed by Goldmann Applanation tonometry
Tmax of RO7058584	Up to Day 8	Tmax is the time to maximum observed plasma concentration.

Locations (8): Arizona Eye Center
🇺🇸
Chandler, Arizona, United States
Eye Care Centers Management, Inc. (Clayton Eye Center)
🇺🇸
Morrow, Georgia, United States
Rocky Mountain Lions Eye Inst
🇺🇸
Aurora, Colorado, United States
Sall Research Medical Center
🇺🇸
Artesia, California, United States
United Med Res Inst
🇺🇸
Inglewood, California, United States
Eye research foundation
🇺🇸
Newport Beach, California, United States
Coastal Research Associates
🇺🇸
Roswell, Georgia, United States
Texan Eye/Keystone Research
🇺🇸
Austin, Texas, United States