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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT03293992

Collaborator

(none)

Enrollment

Locations

Arms

2.4

Actual Duration (Months)

3.4

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Open-angle Ocular Hypertension	Drug: 0.01% RO7058584 Drug: 0.1% RO7058584 Drug: 1% RO7058584 Drug: Matching Placebo Drug: Latanoprost 0.005%	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 10, 2017

Actual Primary Completion Date :

Dec 15, 2017

Actual Study Completion Date :

Dec 21, 2017

Arms and Interventions

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: 0.1% RO7058584 Once daily morning administration for 7 days Drug: Matching Placebo Once daily morning administration for 7 days
Experimental: 1% RO7058584 or Matching Placebo	Drug: 1% RO7058584 Once daily morning administration for 7 days Drug: Matching Placebo 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

Outcome Measures

Primary Outcome Measures

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 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 [7 days]
IOP will be assessed by Goldman Applanation tonometry.

Secondary Outcome Measures

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
Cmax of RO7058584 [Up to Day 8]
Cmax is the maximum observed plasma concentration.
Tmax of RO7058584 [Up to Day 8]
Tmax is the time to 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Eye Center	Chandler	Arizona	United States	85225
2	Sall Research Medical Center	Artesia	California	United States	90701
3	United Med Res Inst	Inglewood	California	United States	90301
4	Eye research foundation	Newport Beach	California	United States	92663
5	Rocky Mountain Lions Eye Inst	Aurora	Colorado	United States	80045
6	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia	United States	30260
7	Coastal Research Associates	Roswell	Georgia	United States	30076
8	Texan Eye/Keystone Research	Austin	Texas	United States	78731

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT03293992

Other Study ID Numbers:

BP39863

First Posted:

Sep 26, 2017

Last Update Posted:

Mar 31, 2020

Last Verified:

Mar 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 31, 2020