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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT02622334

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

6.4

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: Latanoprost Drug: Placebo Drug: RO5093151	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 29, 2015

Actual Primary Completion Date :

Jul 28, 2016

Actual Study Completion Date :

Jul 28, 2016

Arms and Interventions

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: Latanoprost Latanoprost is a ophthalmic solution, available in dose strength as 0.005%. Drug: RO5093151 RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.

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: Latanoprost

Latanoprost is a ophthalmic solution, available in dose strength as 0.005%.

Drug: RO5093151

RO5093151 is a ophthalmic solution, available in dose strengths as 0.1%, 0.5% and 1%.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sall Research Medical Center	Artesia	California	United States	90701
2	Rocky Mountain Lions Eye Inst	Aurora	Colorado	United States	80045
3	Eye Care Centers Management, Inc. (Clayton Eye Center)	Morrow	Georgia	United States	30260
4	New York Eye and Ear Infirmary of Mt. Sinai; New York Glaucoma Research Institute	New York	New York	United States	10003
5	Cornerstone Eye Care, Div of Cornerstone Health Care	High Point	North Carolina	United States	27262
6	West Virginia University Eye Institute	Morgantown	West Virginia	United States	26506
7	Singapore National Eye Centre; Glaucoma Department	Singapore		Singapore	168751