Retinopathy, Diabetic
Conditions
Keywords
Diabetic Macular Edema
Brief summary
The purpose of this study is to characterize the systemic and ocular safety and tolerability, pharmacokinetics, exploratory efficacy and pharmacodynamics of 3 months of repeat administration of oral darapladib in diabetic macular edema patients with centre involvement.
Detailed description
This is a multi-national, multi-centre, randomised, double-masked, placebo-controlled, parallel-group study of repeat oral administration of 160 mg darapladib for 3 months in adult subjects with DME with centre involvement. Eligible subjects will be randomised in a 2:1 ratio of active treatment to placebo, with the placebo group to allow a comparison of safety between treatment arms and to minimize the open label effect that can be observed with the visual acuity endpoint. The primary aim of the study is to determine the effect of repeat doses of darapladib on the mean change from baseline of both best-corrected visual acuity (BCVA) and spectral domain OCT (SD-OCT) centre subfield. The study eye will be examined for changes over the life of the study. As this investigational treatment is systemic, the fellow eye may be examined in tandem to provide additional data.
Interventions
DRUGdarapladib
Experimental compound 160 mg dose
DRUGplacebo
Placebo to match
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A female subject is eligible to participate if she is of: Non-childbearing potential or child-bearing potential and agrees to contraception for an appropriate period of time * Diagnosis of diabetes mellitus (type 1 or type 2) * Confirmation of DME in the study eye by angiography * Confirmation of retinal thickening in the study eye by study doctor * Best corrected visual acuity score of 78-24 letters in the study eye
Exclusion criteria
* Additional eye disease in the study eye that could compromise study assessments * Intraocular surgery, or laser photocoagulation in the study eye within 3 months of dosing * Uncontrolled intraocular pressure in the study eye despite treatment with glaucoma medication * Uncontrolled diabetes * Certain types of liver disease * Severe reduction in kidney function OR removal of a kidney OR kidney transplant * Blood pressure higher than normal despite lifestyle changes and treatment with medications * Certain medications that may interfere with the study medication or eye assessments (these will be identified by the study doctor) * Current severe heart failure * Severe asthma that is poorly controlled with medication * Previous severe allergic reaction to food, medications, drink, insect stings, etc * If both birth parents are at least 50% Japanese, Chinese, or Korean ancestry, must have a blood sample collected for Lp-PLA2 activity. Those with Lp-PLA2 activity less than or equal to 20.0 nmol/min/mL are excluded * Recent participation in a study of an investigational medication * Any other reason the investigator deems the subject should not participate in the study * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Spectral Domain Optical Coherance Tomography | 3 months | Mean change from baseline in SD-OCT after 3 months of treatment |
| Change from baseline in Visual Acuity as measured by ETDRS BCVA | 3 months | Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) after 3 months of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pharmacodynamic LP-PLA2 enzyme inhibition | 3 months | Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit |
| Changes in Retinal Anatomy | 3 months | Changes in retinal anatomy as assessed by fluorescein angiography and fundus photography and SD-OCT in the study eye |
| Plasma concentration versus time curve (AUC) of study drug | 3 months | Plasma Pharmacokinetic parameters of darapladib as data permit |
| Peak plasma concentration (Cmax) of study drug | 3 months | Plasma Pharmacokinetic parameters of darapladib as data permit |
| Safety and Tolerability as assessed by change from baseline in outcome measures | 3 months | Safety and tolerability as assesed by: change from baseline in blood pressure and heart rate; assessed by change from baseline in complete ophthalmic exam and visual acuity; assessed by change from baseline in clinical laboratory tests; assessed by change from baseline in the collection of adverse events |
Countries
Australia, Denmark, Germany, Italy, Netherlands
Outcome results
None listed