Clinical trial NCT02622334: A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO5093151 in Patients With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (OHT).
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glaucoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-12-04
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 12 weeks
measure: Changes in vital signs, electrocardiogram (ECG), opthalmologic assessments, and clinical laboratory results
timeFrame: Up to 12 weeks
measure: 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
timeFrame: Baseline (Day 1) and Day 8
Secondary outcomes:
measure: Change in IOP at matched clock-times after 7 days of treatment vs baseline (diurnal IOP) and between RO5093151 and latanoprost
timeFrame: Baseline and Day 8
measure: Maximum observed plasma concentration (Cmax)
timeFrame: 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
measure: Time to maximum observed plasma concentration (Tmax)
timeFrame: 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
measure: Concentration at the end of a dosing interval before the next dose administration (Ctrough)
timeFrame: 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
measure: Area under the plasma concentration versus time curve from zero to 24 h post-dose (AUC0-24)
timeFrame: 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
measure: Area under the plasma concentration versus time curve up to the last measurable concentration (AUClast)
timeFrame: 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
measure: Apparent terminal half-life (T1/2)
timeFrame: 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
Other outcomes:
Locations:
city: Artesia
country: United States
facility: Sall Research Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Lions Eye Inst
state: Colorado
city: Morrow
country: United States
facility: Eye Care Centers Management, Inc. (Clayton Eye Center)
state: Georgia
city: New York
country: United States
facility: New York Eye and Ear Infirmary of Mt. Sinai; New York Glaucoma Research Institute
state: New York
city: High Point
country: United States
facility: Cornerstone Eye Care, Div of Cornerstone Health Care
state: North Carolina
city: Morgantown
country: United States
facility: West Virginia University Eye Institute
state: West Virginia
city: Singapore
country: Singapore
facility: Singapore National Eye Centre; Glaucoma Department
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: