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
Overview
- Phase
- Phase 2
- Intervention
- darapladib
- Conditions
- Retinopathy, Diabetic
- Sponsor
- GlaxoSmithKline
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Change from baseline in Visual Acuity as measured by ETDRS BCVA
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
darapladib
darapladib dosed at 160 mg once daily
Intervention: darapladib
placebo
Placebo to match once daily
Intervention: placebo
Outcomes
Primary Outcomes
Change from baseline in Visual Acuity as measured by ETDRS BCVA
Time Frame: 3 months
Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) after 3 months of treatment
Change from baseline in Spectral Domain Optical Coherance Tomography
Time Frame: 3 months
Mean change from baseline in SD-OCT after 3 months of treatment
Secondary Outcomes
- Plasma concentration versus time curve (AUC) of study drug(3 months)
- Safety and Tolerability as assessed by change from baseline in outcome measures(3 months)
- Changes in Retinal Anatomy(3 months)
- Changes in Pharmacodynamic LP-PLA2 enzyme inhibition(3 months)
- Peak plasma concentration (Cmax) of study drug(3 months)