Diabetic macular edema with centre involvement MedDRA version: 14.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema System Organ Class: 10015919 - Eye disorders
Conditions
Interventions
Product Name: Darapladib
Product Code: SB-480848
Pharmaceutical Form: Gastro-resistant coated tablet
INN or Proposed INN: Darapladib
Current Sponsor code: SB-480848
Concentration unit: mg milligram(s)
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 1. 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 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. 5. Best corrected visual acuity score of 78-24 letters (Snellen equivalent ~20/32 to 20/320) in the study eye 6. Subject is willing and able to return for all study visits, and is willing and able to comply with all protocol requirements and procedures 7. 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
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 the 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 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 16. Uncontrolled diabetes as indicated by HbA1c >10% at screening 17. 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 18. 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 19. Severe renal impairment (e.g., patients with an estimated glomular filtration rate (GFR) 160mmHg or diastolic blood pressure >110mmHg (mean of 3 measurements according to protocol-specified conditions) 21. Current severe heart failure (New York Heart Association class III or IV) 22. QTcF > 480msec in any subject including those with Bundle Branch Block 23. Severe asthma that is poorly controlled on pharmacotherapy 24
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of darapladib administered as oral daily doses for 3 months on best-corrected visual acuity (BCVA) and spectral domain OCT (SD-OCT) centre subfield of the study eye in adult subjects with centre-involved DME.;Secondary Objective: Secondary Objectives: • To determine the effect of darapladib administered as oral daily doses for 3 months on retina anatomy of the study eye in adult subjects with centre-involved DME • To assess safety and tolerability of darapladib in adult subjects with centre-involved DME • To determine the pharmacokinetic and pharmacodynamic profiles of darapladib in adult subjects with centre-involved DME, as data permit Exploratory Endpoints: • To determine the effect of darapladib administered as oral daily doses for 3 months on best-corrected visual acuity (BCVA) and spectral domain OCT (SD-OCT) centre subfield in the fellow eye in adult subjects with centre-involved DME • To determine the effect of darapladib administered as oral daily doses for 3 months on retina anatomy of the fellow eye in adult subjects with centre-involved DME;Primary end point(s): Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) and SD-OCT2 centre subfield retinal thickness in the study eye. ETDRS = Early Treatment in Diabetic Retinopathy Study SD-OCT = Spectral Domain Optical Coherence Tomography ;Timepoint(s) of evaluation of this end point: 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • Changes in retinal anatomy as assessed by fluorescein angiography (leakage area), fundus photography (retinal thickening area) and SD-OCT (macular volume, subretinal fluid, intraretinal cysts) in the study eye • Safety and tolerability assessed by complete ophthalmic examination, visual acuity, vital sign measures (heart rate and blood pressure), clinical laboratory tests, clinical monitoring and adverse event reporting • Plasma pharmacokinetic parameters (Cmax, AUC0-t, apparent volume of distribution and apparent clearance, etc) of darapladib as data permit • Pharmacodynamic parameters (Lp-PLA2 activity inhibition) of darapladib as data permit Exploratory Endpoints: • Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) and SD-OCT centre subfield retinal thickness in the fellow eye, as data permit • Changes in retinal anatomy as assessed by fluorescein angiography (leakage area), fundus photography (retinal thickening area) and SD-OCT (macular volume, subretinal fluid, intraretinal cysts) in the fellow eye, as data permit;Timepoint(s) of evaluation of this end point: Screening and month 3 at a minimum | — |
Countries
Australia, Denmark, Germany, Italy, Netherlands
Contacts
Public ContactGSK Clinical Support Helpdesk
GlaxoSmithKline
Outcome results
None listed