Glaucoma
Conditions
Brief summary
The purpose of the study is to assess the safety, tolerability, and IOP effects of RO5093151 following 7 days of topical ocular treatment in patients with primary open angle glaucoma or ocular hypertension.
Interventions
DRUGLatanoprost
Latanoprost is a ophthalmic solution, available in dose strength as 0.005%.
DRUGPlacebo
Matching placebo formulation will be administered in Part A.
DRUGRO5093151
RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ocular hypertension (OHT) or primary open angle glaucoma (POAG) in at least one eye (qualifying eye) as determined by the Investigator at screening or based on a reliable and documented assessment done within the last 6 months prior to screening provided that no progression of visual field damage is expected * At baseline visit, intraocular pressure (IOP) \>= 24 mmHg in the morning and \>= 21 mmHg in the afternoon measurement in at least one eye (qualifying eye = study eye) and =\< 34 mmHg at all time points in both eyes * Best corrected logMAR visual acuity score of 0.7 (20/100 Snellen) or better in each eye as measured by ETDRS visual acuity test at screening * Central corneal pachymetry measurement 420 to 620 micrometer in qualifying eye at screening * Cup-to-disk ratio =\< 0.8 (both eyes) at screening * Anterior chamber angle is open and non-occludable as confirmed by the Investigator by gonioscopy examination at screening
Exclusion criteria
* History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease (multiple allergies, seasonal allergy is acceptable), metabolic disorder, cancer or cirrhosis * Uncontrolled hypertension (SBP \>= 160 mmHg and/or DBP \>= 100 mmHg) despite treatment at the time of screening confirmed by the average of \>= 3 blood pressure measurements, properly measured with well-maintained equipment * Clinically significant abnormalities in laboratory test results at screening * Hypersensitivity to RO5093151 or any of the components of its formulation, or hypersensitivity to latanoprost or any of the components of its formulation (Part B only) * Donation of blood over 500 mL within three months prior to screening * Positive result on hepatitis B (HBV), hepatitis C (HCV), or HIV 1 and 2 * Presence of narrow angle (=\< grade 2 Shaffer gonioscopic classification) or complete or partial closure, as measured by gonioscopy or at risk for angle closure as assessed by the Investigator * Other forms of glaucoma than POAG or OHT in the study eye * Any abnormality preventing reliable applanation tonometry * Any clinically significant corneal scarring, haze or opacity * Patient uncooperativeness that restricts adequate examination of IOP, ocular fundus or anterior chamber * Evidence of clinically significant blepharitis, concurrent infectious/non-infectious conjunctivitis, keratitis or uveitis * History or signs of penetrating ocular trauma. Uneventful (uncomplicated) cataract surgery performed 3 months prior to screening is allowed * According to the Investigator's best judgment, risk of visual field or visual acuity worsening in either eye as a consequence of glaucoma progression or consequence of participation in the trial (i.e., during washout of ocular hypotensive medications or treatment with placebo) or any other ocular disease * Unable to safely stop ocular hypotension medications prior to randomization according to the required minimum washout periods * History of any ocular filtering surgical intervention, previous glaucoma intraocular surgery, or laser trabeculoplasty * History of refractive surgery (laser assisted in-situ keratomileusis, laser epithelial keratomileusis, photorefractive keratectomy, phototherapeutic keratectomy) * Any other intraocular surgery within 6 months of screening * Advanced age-related macular degeneration (wet or dry), vitreous hemorrhage, diabetic retinopathy or any progressive retinal or optic nerve disease from any cause other than glaucoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events | Up to 12 weeks |
| Changes in vital signs, electrocardiogram (ECG), opthalmologic assessments, and clinical laboratory results | Up to 12 weeks |
| Change in mean IOP after 7 days treatment vs baseline: change from baseline for RO5093151 and latanoprost and difference in change from baseline between RO5093151 and latanoprost | Baseline (Day 1) and Day 8 |
Secondary
| Measure | Time frame |
|---|---|
| Concentration at the end of a dosing interval before the next dose administration (Ctrough) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
| Area under the plasma concentration versus time curve from zero to 24 h post-dose (AUC0-24) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
| Change in IOP at matched clock-times after 7 days of treatment vs baseline (diurnal IOP) and between RO5093151 and latanoprost | Baseline and Day 8 |
| Apparent terminal half-life (T1/2) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
| Area under the plasma concentration versus time curve up to the last measurable concentration (AUClast) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
| Maximum observed plasma concentration (Cmax) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
| Time to maximum observed plasma concentration (Tmax) | Day 1: Pre-dose (morning); 30 minutes, 1, 4, 8, 11 (evening pre-dose) and 12 hours post-dose; Day 7: Pre-dose (evening), 1, 12 (Day 8), 16 (Day 8), 20 (Day 8) hours post-dose |
Countries
Singapore, United States
Outcome results
None listed