A Phase 2 Clinical Study to Investigate Effects of Darapladib in Subjects With Diabetic Macular Edema

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Multi-national, Multi-centre, Double Masked, Randomised, Placebo Controlled, Parallel-group Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Darapladib Administered for 3 Months to Adult Subjects With Diabetic Macular Edema With Centre Involvement

Conditions
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Retinopathy, Diabetic

Intervention / Treatment
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* Drug: darapladib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: darapladib<br>darapladib dosed at 160 mg once daily | Drug: darapladib<br>* Experimental compound 160 mg dose<br>|
| Placebo Comparator: placebo<br>Placebo to match once daily | Drug: placebo<br>* Placebo to match<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Visual Acuity as measured by ETDRS BCVA | Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) after 3 months of treatment | 3 months | 
| Change from baseline in Spectral Domain Optical Coherance Tomography | Mean change from baseline in SD-OCT after 3 months of treatment | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Retinal Anatomy | Changes in retinal anatomy as assessed by fluorescein angiography and fundus photography and SD-OCT in the study eye | 3 months | 
| Safety and Tolerability as assessed by change from baseline in outcome measures | 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 | 3 months | 
| Changes in Pharmacodynamic LP-PLA2 enzyme inhibition | Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit | 3 months | 
| Peak plasma concentration (Cmax) of study drug | Plasma Pharmacokinetic parameters of darapladib as data permit | 3 months | 
| Plasma concentration versus time curve (AUC) of study drug | Plasma Pharmacokinetic parameters of darapladib as data permit | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema