A 3 month Study of Darapladib to Treat Diabetic Macular Edema (DME).

Phase 1

Conditions: Diabetic macular edema with centre involvement
MedDRA version: 14.0Level: LLTClassification code 10057934Term: Diabetic macular edemaSystem Organ Class: 10015919 - Eye disorders
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2011-002944-28-DK

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 54

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Subject is at least 18 years of age inclusive, at the time of signing the informed consent
2. A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or Investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use
contraception until follow up visit
3. Diagnosis of diabetes mellitus (type 1 or type 2)
4. Confirmation of DME in the study eye by investigator-determined fluorescein angiography
5. Retinal thickening (diabetic macular edema) involving the centre of the fovea in the study eye as defined by investigator-determined SD-OCT central subfield thickness > 330 microns for Heidelberg Spectralis and >310 for Zeiss Cirrus; if both eyes are eligible, the eye with the greater OCT centre subfield score is selected as the study eye.
6. Best corrected visual acuity score of 78-24 letters (Snellen equivalent ~20/32 to 20/320) in the study eye
7. Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures
8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
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 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Ocular
1. Additional eye disease in the study eye that could compromise assessment of BCVA or imaging of the posterior pole by fundus photography, fluorescein angiography, or spectral domain OCT, or is likely to require intervention during the ~4 month study
(e.g. cataract, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa)
2. Active proliferative diabetic retinopathy in the study eye
3. Ischemic maculopathy on fluorescein angiography defined as a total area of capillary loss greater than 2 disc areas (> 5mm2) within the ETDRS macular grid or a foveal avascular zone greatest linear diameter of > 1000 microns
4. History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment
5. Intraocular surgery in the study eye within 3 months of dosing
6. Laser photocoagulation in study eye within 3 months of dosing
7. Use of intravitreal ranibizumab in the study eye within 90 days of dosing
8. Use of intravitreal bevacizumab in the study eye within 180 days of dosing
9. Use of intraocular steroids in the study eye within 180 days of dosing
10. Use of intravitreal bevacizumab in the fellow eye or expected need for intravitreal bevacizumab in the fellow eye during the course of the study
11. Best-corrected visual acuity score by electronic ETDRS < 56 letters in the fellow eye at screening
12. Use of any systemically administered anti-angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational, within 6 months of dosing.
13. Evidence of vitreomacular traction as determined by the Investigator.
14. Uncontrolled intraocular pressure >22 mmHg in the study eye despite treatment with glaucoma medication
15. Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
Non-ocular
1. Uncontrolled diabetes as indicated by HbA1c >10% at screening
2. Evidence of clinical instability or abnormal clinical laboratory findings prior to randomisation that, in the opinion of the Investigator, makes the subject unsuitable for the study
3. Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones) or evidence of abnormal liver function tests [total bilirubin or alkaline phosphatase >1.5 x upper limit of normal (ULN); or ALT or AST >2.5 x ULN] or other hepatic abnormalities that in the opinion of the Investigator would preclude the subject from participation in the study
4. Severe renal impairment (e.g., patients with an estimated glomular filtration rate (GFR) <30 mL/min/1.73m2 or receiving chronic dialysis) or history of nephrectomy or kidney transplant (regardless of renal function)
5. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy; systolic blood pressure >160mmHg or diastolic blood pressure >110mmHg (mean of 3 measurements according to protocol-specified conditions)
6. Current severe heart failure (New York Heart Association class III or IV)
7. QTcF > 480msec in any subject including those with Bundle Branch Block
8. Severe asthma that is poorly controlled on pharmacotherapy
9. History of anaphylaxis, anaphylac