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

Glaucoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02622334
• Other study ID #: BP30002
• Status: Completed
• Phase: Phase 1
• First received: December 2, 2015
• Last updated: March 13, 2018
• Start date: December 29, 2015
• Est. completion date: July 28, 2016

Study information

• Verified date: March 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 28, 2016
• Est. primary completion date: July 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Open-Angle
• Hypertension
• Ocular Hypertension

Intervention

Drug:
• Latanoprost
Latanoprost is a ophthalmic solution, available in dose strength as 0.005%.
• Placebo
Matching placebo formulation will be administered in Part A.
• RO5093151
RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.

Locations

Country	Name	City	State
Singapore	Singapore National Eye Centre; Glaucoma Department	Singapore
United States	Sall Research Medical Center	Artesia	California
United States	Rocky Mountain Lions Eye Inst	Aurora	Colorado
United States	Cornerstone Eye Care, Div of Cornerstone Health Care	High Point	North Carolina
United States	West Virginia University Eye Institute	Morgantown	West Virginia
United States	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia
United States	New York Eye and Ear Infirmary of Mt. Sinai; New York Glaucoma Research Institute	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events		Up to 12 weeks
Primary	Changes in vital signs, electrocardiogram (ECG), opthalmologic assessments, and clinical laboratory results		Up to 12 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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