A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO5093151 in Patients With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (OHT).

A MULTIPLE-CENTER, INVESTIGATOR/SUBJECT MASKED, ADAPTIVE, MULTIPLE ASCENDING DOSE, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF RO5093151 FOLLOWING 7 DAYS ADMINISTRATION IN PATIENTS WITH PRIMARY OPEN ANGLE GLAUCOMA OR OCULAR HYPERTENSION

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.

Study Overview

• Status: Completed
• Conditions: Glaucoma
• Intervention / Treatment: Drug: Placebo; Drug: RO5093151; Drug: Latanoprost

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 168751
    • Singapore National Eye Centre; Glaucoma Department
• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
  • 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)
  • New York
    • New York, New York, United States, 10003
      • New York Eye and Ear Infirmary of Mt. Sinai; New York Glaucoma Research Institute
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Cornerstone Eye Care, Div of Cornerstone Health Care
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Eye Institute

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Participants will receive up to 3 multiple ascending dose levels with the starting dose of 0.1% RO5093151 (topical ocular instillation) and sequentially 0.5% and 1% RO5093151 doses or placebo (3:1, active:placebo) twice a day (BID) on Day 1 and once a day (QD) for 6 days.	Drug: Placebo; Matching placebo formulation will be administered in Part A.; Drug: RO5093151; RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.
Experimental: Part B; Participants will receive highest feasible dose (HFD) or maximum tolerated dose (MTD) of RO5093151 from Part A or 0.005% latanoprost (topical ocular instillation) once daily for 7 days.	Drug: RO5093151; RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.; Drug: Latanoprost; Latanoprost is a ophthalmic solution, available in dose strength as 0.005%.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2015
• Primary Completion (Actual): July 28, 2016
• Study Completion (Actual): July 28, 2016

Study Registration Dates

• First Submitted: December 2, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 4, 2015

Study Record Updates

• Last Update Posted (Actual): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

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: BP30002