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
Primary Purpose
Glaucoma, Open-angle, Ocular Hypertension
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
0.01% RO7058584
0.1% RO7058584
1% RO7058584
Matching Placebo
Latanoprost 0.005%
Sponsored by
About this trial
This is an interventional treatment trial for Glaucoma, Open-angle
Eligibility Criteria
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
Sites / Locations
- Arizona Eye Center
- Sall Research Medical Center
- United Med Res Inst
- Eye research foundation
- Rocky Mountain Lions Eye Inst
- Eye Care Centers Management, Inc. (Clayton Eye Center)
- Coastal Research Associates
- Texan Eye/Keystone Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
0.01% RO7058584 or Matching Placebo
0.1% RO7058584 or Matching Placebo
1% RO7058584 or Matching Placebo
RO7058584 and Latanoprost 0.005%
Arm Description
Outcomes
Primary Outcome Measures
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.
Incidence of Abnormal Laboratory Findings
Incidence of Blood Pressure Abnormalities
Incidence of Pulse Rate Abnormalities
Incidence of Electrocardiogram (ECG) Findings
Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration
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
IOP will be assessed by Goldmann Applanation tonometry
Cmax of RO7058584
Cmax is the maximum observed plasma concentration.
Tmax of RO7058584
Tmax is the time to maximum observed plasma concentration.
Ctrough of RO7058584
Ctrough is the concentration at the end of a dosing interval before the next dose administration.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03293992
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
October 10, 2017 (Actual)
Primary Completion Date
December 15, 2017 (Actual)
Study Completion Date
December 21, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma, Open-angle, Ocular Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
0.01% RO7058584 or Matching Placebo
Arm Type
Experimental
Arm Title
0.1% RO7058584 or Matching Placebo
Arm Type
Experimental
Arm Title
1% RO7058584 or Matching Placebo
Arm Type
Experimental
Arm Title
RO7058584 and Latanoprost 0.005%
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
0.01% RO7058584
Intervention Description
Once daily morning administration for 7 days
Intervention Type
Drug
Intervention Name(s)
0.1% RO7058584
Intervention Description
Once daily morning administration for 7 days
Intervention Type
Drug
Intervention Name(s)
1% RO7058584
Intervention Description
Once daily morning administration for 7 days
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Once daily morning administration for 7 days
Intervention Type
Drug
Intervention Name(s)
Latanoprost 0.005%
Intervention Description
Once daily morning or evening dosing
Primary Outcome Measure Information:
Title
Incidence, Severity, and Causal Relationship of Ocular and Systemic Adverse Events (AEs)
Description
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.
Time Frame
Up to 12 weeks
Title
Incidence of Abnormal Laboratory Findings
Time Frame
Up to 12 weeks
Title
Incidence of Blood Pressure Abnormalities
Time Frame
Up to 12 weeks
Title
Incidence of Pulse Rate Abnormalities
Time Frame
Up to 12 weeks
Title
Incidence of Electrocardiogram (ECG) Findings
Time Frame
Up to 12 weeks
Title
Change From Baseline in Mean Intraocular pressure (IOP) After 7 Days of Study Drug Administration
Description
IOP will be assessed by Goldman Applanation tonometry.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Intraocular pressure (IOP) at Matched Clock-Times After 7 Days of Study Drug Administration
Description
IOP will be assessed by Goldmann Applanation tonometry
Time Frame
7 days
Title
Cmax of RO7058584
Description
Cmax is the maximum observed plasma concentration.
Time Frame
Up to Day 8
Title
Tmax of RO7058584
Description
Tmax is the time to maximum observed plasma concentration.
Time Frame
Up to Day 8
Title
Ctrough of RO7058584
Description
Ctrough is the concentration at the end of a dosing interval before the next dose administration.
Time Frame
Up to Day 8
Title
AUC0-24h of RO7058584
Description
AUC0-24h is the area under the plasma concentration versus time curve (AUC) from Time 0 to 24 h post-dose.
Time Frame
Up to Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Eye Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85225
Country
United States
Facility Name
Sall Research Medical Center
City
Artesia
State/Province
California
ZIP/Postal Code
90701
Country
United States
Facility Name
United Med Res Inst
City
Inglewood
State/Province
California
ZIP/Postal Code
90301
Country
United States
Facility Name
Eye research foundation
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Rocky Mountain Lions Eye Inst
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Eye Care Centers Management, Inc. (Clayton Eye Center)
City
Morrow
State/Province
Georgia
ZIP/Postal Code
30260
Country
United States
Facility Name
Coastal Research Associates
City
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
Texan Eye/Keystone Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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