A placebo controlled trial investigating the safety and effectiveness of AZD4017 in patients with raised intra-ocular pressure

Conditions: Raised Intra-Ocular Pressure or primaryopen angle glaucoma (POAG) on anti-glaucoma monotherapy that has been stable indose for at least 30 days prior to screening.
MedDRA version: 14.1Level: LLTClassification code 10036719Term: Primary open angle glaucomaSystem Organ Class: 10015919 - Eye disorders
MedDRA version: 14.1Level: LLTClassification code 10022809Term: Intraocular pressure raisedSystem Organ Class: 10022891 - Investigations
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2010-020932-20-SE

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures.
2.Non-diabetic males and females aged 18 to 80 years, inclusive.
3.Must have a diagnosis of intra-ocular hypertension (raised IOP), or primary open angle glaucoma (POAG), with IOP >20 mmHg and =36 mmHg in the study eye, and is currently prescribed a stable dose of a single anti-glaucoma medication that began at least 30 days prior to the screening visit;
OR
Must have a diagnosis of intra-ocular hypertension (raised IOP), defined as an IOP =22 mmHg and =36 mmHg in the study eye while not on anti-glaucoma medication.
4.Must have a best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score of +0.6 logarithm of the minimum angle of resolution (logMAR [Snellen equivalent of 20/80]) or better in each eye.
5.Must have a <5 mmHg difference in mean IOP between eyes at 9AM at Baseline (Visit 3).
6.Male patients must be willing to use barrier contraception with spermicide, ie, condoms, from the day of first dosing until 3 months after dosing with IP.
7.Placebo treatment for duration of the study must not be considered detrimental to the patient.
8.Must be willing to discontinue soft contact lens wear from 7 days prior to Visit 3 until the completion of the final study visit or to discontinue hard contact lens wear from 1 month prior to Visit 3 until the completion of the final study visit.
9.Must be able to understand the consent form and comply with study requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

Ocular Exclusion Criteria:
- Have uncontrolled intra-ocular hypertension (>36 mmHg).
- Have experienced a significant visual field loss or showed evidence of progressive visual field loss within the last year (as defined by >1 dB/yr average loss or vision threatening new defect). Patients with severe central field loss in either eye is defined as a sensitivity =10 dB in at least 2 of the 4 visual field test points closest to the point of fixation.
- Have narrow anterior chamber angles in either eye judged potentially occludable if pupillary dilatation were to occur, evidence or history of acute or chronic angle closure, or is at risk for angle closure as evidenced by anterior chamber angle less than grade 2 according to Schaffer classification, as measured by gonioscopy.

General Exclusion Criteria:
- Women of child-bearing potential (WOCBP).
- Have uncontrolled systemic hypertension
(BP >150/90).
- Are receiving systemic (including vaginal/rectal) or inhaled steroid treatment at the time of the screening visit (Visit 2).
- Have any screening laboratory abnormality that, in the investigator’s judgement, is considered to be clinically significant.
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results of the subject’s ability to participate in the study.
- Had a change in dose or initiation of systemic therapies (including herbal medications, vitamins, and nutrient supplements [eg, fish oil, and zinc]) that can substantially affect IOP or the study outcome, such as (but not limited to) alpha adrenergic agents, beta-adrenergic blockers, calcium channel blockers, carbonic anhydrase inhibitors, angiotensin-converting enzyme inhibitors or other antihypertensive medications within 30 days prior to the screening visit (Visit 2), or anticipates a change in such therapy during the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the efficacy of systemically administered AZD4017, compared with placebo, over a 28-day period in patients with raised intra-ocular pressure (IOP) not on anti-glaucoma medication or patients with raised IOP or primary open angle glaucoma (POAG) on anti-glaucoma monotherapy that has been stable in dose for at least 30 days prior to screening. The primary efficacy variable will be the percentage decrease in IOP compared with baseline after 28 days of treatment.;Secondary Objective: • To compare the safety and tolerability of systemically administered AZD4017 with placebo, by evaluation of safety variables.<br>• To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of AZD4017;Primary end point(s): Percentage decrease from baseline in IOP at endpoint;Timepoint(s) of evaluation of this end point: Final visit assessment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1 - Number of patients experiencing a clinically relevant decrease in IOP <br>2 - Change from baseline to final visit in eye exams, IOP measurements, corneal thickness, clinical laboratory test results, and vital signs<br>3 - Incidence of AEs, DAEs, SAEs;Timepoint(s) of evaluation of this end point: 1 - Day 28<br>2 - Throughout study participation<br>3 - Throughout study participation

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