Dose Finding Clinical Trial With SYL040012 to Evaluate the Tolerability and Effect on Intraocular Pressure in Subjects With Ocular Hypertension or Open Angle Glaucoma

The aim of this dose-finding clinical trial is to evaluate the systemic tolerability, local tolerability and intraocular pressure lowering effect of three different doses of SYL040012 in subjects with ocular hypertension or open-angle glaucoma.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Open Angle Glaucoma
• Intervention / Treatment: Drug: SYL040012; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallin, Estonia, 10138
    • East Tallin Central Hospital
  • Tallin, Estonia, 13419
    • Eye Clinic Dr. Krista Turman
• Germany
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Köln, Germany, 50937
    • Uniklinik Köln
  • Mainz, Germany, 55131
    • Universitaetsklinikum Mainz
• Spain
  • Barcelona, Spain, 08022
    • Institut Catala de Retina
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Valladolid, Spain, 47011
    • Instituto de Oftalmobiología Aplicada
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must provide signed informed consent prior to participation in any study-related procedures.
• Male and female subjects in good or fair general health as assessed by the investigator.
• ≥18 years of age.
• Previous history or newly diagnosed elevated IOP (≥21 mmHg) with or without open-angle glaucoma in both eyes.
• Normal result, or result typical for open-angle glaucoma of the following assessments in both eyes or available results in writing within the last 3 months prior to baseline period i.e. up to 4 months before Day 1, on condition that no new ocular signs or symptoms (e.g. marked deterioration of vision, eye pain) has occurred since then which would justify a repeat examination:
• Visual field 24-2 or equivalent
• Optical coherence tomography (OCT)
• Best corrected visual acuity ≥0.5 (20/40) on the Snellen chart, or ≤ 0.3 logMAR
• Schirmer test (lacrimation)
• Funduscopy

Exclusion Criteria:

• Pregnant or breastfeeding females or those with a positive pregnancy test. Females of childbearing potential who will not use a medically acceptable contraceptive method from selection and during the hole study.
• Females of childbearing potential not willing to use a medically acceptable contraceptive method from enrolment until after the follow-up visit.
• Any current disease or condition that might compromise the respiratory, cardiovascular, endocrine, neurological, haematological, renal, or gastrointestinal function.
• Previous chronic processes or with rebound characteristics that could interfere with the study according to the investigator's judgment.
• Body temperature.
• Intolerability of any components of SYL040012 or placebo.
• Unable to comply with the clinical trial requirements as judged by the investigator.
• Beta blockers or corticosteroids use (other than cutaneous or intra-articular) for the treatment of concurrent diseases, even if sporadically, or any ocular or nasal vasoconstrictor treatment in the last 15 days prior to the first investigational product administration
• Previous refractive surgery; cataract extraction in the last 6 months
• Previous surgery for glaucoma.
• Participation in a clinical trial within 2 months before the enrolment visit
• Use of any other investigational product within 60 days before the enrolment visit.
• Other drugs for the treatment of concurrent diseases are allowed. However, their dosages should be kept constant throughout the study.
• Use of contact lenses in the last 7 days prior to the first investigational product administration and wearing contact lenses throughout the trial
• History of ocular infection or inflammation within the last 3 months before the enrolment visit
• Angle-closure or pigmentary glaucoma.
• Chronic or current acute eye diseases such as scleritis, uveitis, blepharitis, conjunctivitis, or ocular Herpes simplex virus infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYL040012 eye drops dose A; Ocular topical administration of SYL040012 eye drops dose A	Drug: SYL040012; Ocular topical administration of SYL040012 for 14 consecutive days
Experimental: SYL040012 eye drops dose B; Ocular topical administration of SYL040012 eye drops dose B	Drug: SYL040012; Ocular topical administration of SYL040012 for 14 consecutive days
Experimental: SYL040012 eye drops dose C; Ocular topical administration of SYL040012 eye drops dose C	Drug: SYL040012; Ocular topical administration of SYL040012 for 14 consecutive days
Placebo Comparator: Placebo; Ocular topical administration of placebo eye drops	Drug: Placebo; Ocular topical administration of placebo for 14 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in AUC between IOP Curve Obtained at the Established Time Points and the Same Curve Performed at Baseline Period	14 days + (4-7 days)
Simple Corneal and Conjunctival Evaluation	15 days + (3-6 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Visual acuity, anterior segment and ocular fundus examination as measures of local tolerability.	14 days + (4-7 days)
Physical exploration and laboratory tests as measurements of general tolerability	14 days + (4-7 days)
Assessment of Adverse Events Appearance	14 days + (4-7 days)

Collaborators and Investigators

• Sponsor: Sylentis, S.A.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: November 12, 2012
• First Submitted That Met QC Criteria: November 28, 2012
• First Posted (Estimate): December 3, 2012

Study Record Updates

• Last Update Posted (Estimate): June 10, 2013
• Last Update Submitted That Met QC Criteria: June 7, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Ocular Hypertension; Glaucoma; IOP; siRNA; RNAi; beta inhibitor; Open Angle Glaucoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension
• Other Study ID Numbers: SYL040012_III