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

A Phase I, Multi-Center, Randomized, Adaptive, Investigator/Patient Masked, Multiple-Ascending Dose, Placebo and Active Comparator-Controlled Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7058584 Following 7 Days of Topical Instillation of Eye Drops in Patients With Primary Open Angle Glaucoma or Ocular Hypertension

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).

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Glaucoma, Open-angle
• Intervention / Treatment: Drug: 0.01% RO7058584; Drug: Matching Placebo; Drug: 0.1% RO7058584; Drug: 1% RO7058584; Drug: Latanoprost 0.005%

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Arizona Eye Center
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
    • Inglewood, California, United States, 90301
      • United Med Res Inst
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mountain Lions Eye Inst
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Eye Care Centers Management, Inc. (Clayton Eye Center)
    • Roswell, Georgia, United States, 30076
      • Coastal Research Associates
  • Texas
    • Austin, Texas, United States, 78731
      • Texan Eye/Keystone Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 0.01% RO7058584 or Matching Placebo	Drug: 0.01% RO7058584; Once daily morning administration for 7 days; Drug: Matching Placebo; Once daily morning administration for 7 days
EXPERIMENTAL: 0.1% RO7058584 or Matching Placebo	Drug: Matching Placebo; Once daily morning administration for 7 days; Drug: 0.1% RO7058584; Once daily morning administration for 7 days
EXPERIMENTAL: 1% RO7058584 or Matching Placebo	Drug: Matching Placebo; Once daily morning administration for 7 days; Drug: 1% RO7058584; Once daily morning administration for 7 days
EXPERIMENTAL: RO7058584 and Latanoprost 0.005%	Drug: 0.01% RO7058584; Once daily morning administration for 7 days; Drug: 0.1% RO7058584; Once daily morning administration for 7 days; Drug: 1% RO7058584; Once daily morning administration for 7 days; Drug: Latanoprost 0.005%; Once daily morning or evening dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, Severity, and Causal Relationship of Ocular and Systemic Adverse Events (AEs)	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.	Up to 12 weeks
Incidence of Abnormal Laboratory Findings		Up to 12 weeks
Incidence of Blood Pressure Abnormalities		Up to 12 weeks
Incidence of Pulse Rate Abnormalities		Up to 12 weeks
Incidence of Electrocardiogram (ECG) Findings		Up to 12 weeks
Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration	IOP will be assessed by Goldman Applanation tonometry.	7 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 10, 2017
• Primary Completion (ACTUAL): December 15, 2017
• Study Completion (ACTUAL): December 21, 2017

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (ACTUAL): September 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Pharmaceutical Solutions; Ophthalmic Solutions; Latanoprost
• Other Study ID Numbers: BP39863

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No