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

Retinopathy, Diabetic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506895
• Other study ID #: 115403
• Status: Completed
• Phase: Phase 2
• First received: December 21, 2011
• Last updated: November 18, 2016
• Start date: February 2012
• Est. completion date: February 2013

Study information

• Verified date: November 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Macular Edema
• Retinopathy, Diabetic

Intervention

Drug:
• darapladib
Experimental compound 160 mg dose
• placebo
Placebo to match

Locations

Country	Name	City	State
Australia	GSK Investigational Site	East Melbourne	Victoria
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Parramatta	New South Wales
Australia	GSK Investigational Site	Sydney	New South Wales
Denmark	GSK Investigational Site	Glostrup
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Torino	Piemonte
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Australia,  Denmark,  Germany,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change from baseline in Spectral Domain Optical Coherance Tomography	Mean change from baseline in SD-OCT after 3 months of treatment	3 months
Secondary	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
Secondary	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
Secondary	Changes in Pharmacodynamic LP-PLA2 enzyme inhibition	Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit	3 months
Secondary	Peak plasma concentration (Cmax) of study drug	Plasma Pharmacokinetic parameters of darapladib as data permit	3 months
Secondary	Plasma concentration versus time curve (AUC) of study drug	Plasma Pharmacokinetic parameters of darapladib as data permit	3 months

External Links

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