Clinical trial NCT01506895: A Phase 2 Clinical Study to Investigate Effects of Darapladib in Subjects With Diabetic Macular Edema
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinopathy, Diabetic
Keywords: Diabetic Macular Edema
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-01-10
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: Change from baseline in Visual Acuity as measured by ETDRS BCVA
timeFrame: 3 months
measure: Change from baseline in Spectral Domain Optical Coherance Tomography
timeFrame: 3 months
Secondary outcomes:
measure: Changes in Retinal Anatomy
timeFrame: 3 months
measure: Safety and Tolerability as assessed by change from baseline in outcome measures
timeFrame: 3 months
measure: Changes in Pharmacodynamic LP-PLA2 enzyme inhibition
timeFrame: 3 months
measure: Peak plasma concentration (Cmax) of study drug
timeFrame: 3 months
measure: Plasma concentration versus time curve (AUC) of study drug
timeFrame: 3 months
Other outcomes:
Locations:
city: Parramatta
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Sydney
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: East Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Glostrup
country: Denmark
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Padova
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: