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

NCT02622334 | Completed Phase 1

• 1 other identifier: BP30002
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 7

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.

Conditions

Glaucoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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

Study Arms (2)

Part A

EXPERIMENTAL

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; Drug: RO5093151

Part B

EXPERIMENTAL

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; Drug: RO5093151

Interventions

Latanoprost DRUG

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

Part B

Placebo DRUG

Matching placebo formulation will be administered in Part A.

Part A

RO5093151 DRUG

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

Part A; Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Sall Research Medical Center

Artesia, California, 90701, United States

Location

Rocky Mountain Lions Eye Inst

Aurora, Colorado, 80045, United States

Location

Eye Care Centers Management, Inc. (Clayton Eye Center)

Morrow, Georgia, 30260, United States

Location

New York Eye and Ear Infirmary of Mt. Sinai; New York Glaucoma Research Institute

New York, New York, 10003, United States

Location

Cornerstone Eye Care, Div of Cornerstone Health Care

High Point, North Carolina, 27262, United States

Location

West Virginia University Eye Institute

Morgantown, West Virginia, 26506, United States

Location

Singapore National Eye Centre; Glaucoma Department

Singapore, 168751, Singapore

Location

MeSH Terms

Conditions

Glaucoma

Interventions

Latanoprost

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2015
• First Posted: December 4, 2015
• Study Start: December 29, 2015
• Primary Completion: July 28, 2016
• Study Completion: July 28, 2016
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

US (6); SG (1)