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

Ocular Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03293992
• Other study ID #: BP39863
• Status: Completed
• Phase: Phase 1
• Start date: October 10, 2017
• Est. completion date: December 21, 2017

Study information

• Verified date: March 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 21, 2017
• Est. primary completion date: December 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

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

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Open-Angle
• Hypertension
• Ocular Hypertension

Intervention

Drug:
• 0.01% RO7058584
Once daily morning administration for 7 days
• 0.1% RO7058584
Once daily morning administration for 7 days
• 1% RO7058584
Once daily morning administration for 7 days
• Matching Placebo
Once daily morning administration for 7 days
• Latanoprost 0.005%
Once daily morning or evening dosing

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of Abnormal Laboratory Findings		Up to 12 weeks
Primary	Incidence of Blood Pressure Abnormalities		Up to 12 weeks
Primary	Incidence of Pulse Rate Abnormalities		Up to 12 weeks
Primary	Incidence of Electrocardiogram (ECG) Findings		Up to 12 weeks
Primary	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	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
Secondary	Cmax of RO7058584	Cmax is the maximum observed plasma concentration.	Up to Day 8
Secondary	Tmax of RO7058584	Tmax is the time to maximum observed plasma concentration.	Up to Day 8
Secondary	Ctrough of RO7058584	Ctrough is the concentration at the end of a dosing interval before the next dose administration.	Up to Day 8
Secondary	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