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

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

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.

Study Overview

• Status: Completed
• Conditions: Retinopathy, Diabetic
• Intervention / Treatment: Drug: darapladib; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Parramatta, New South Wales, Australia, 2150
      • GSK Investigational Site
    • Sydney, New South Wales, Australia, 2000
      • GSK Investigational Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • GSK Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • GSK Investigational Site
• Denmark
  • Glostrup, Denmark
    • GSK Investigational Site
• Germany
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
    • Ulm, Baden-Wuerttemberg, Germany, 89075
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 51109
      • GSK Investigational Site
    • Muenster, Nordrhein-Westfalen, Germany, 48145
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • GSK Investigational Site
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20157
      • GSK Investigational Site
  • Piemonte
    • Torino, Piemonte, Italy, 10122
      • GSK Investigational Site
  • Veneto
    • Padova, Veneto, Italy, 35128
      • GSK Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • GSK Investigational Site
  • Rotterdam, Netherlands, 3011 BH
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: darapladib; darapladib dosed at 160 mg once daily	Drug: darapladib; Experimental compound 160 mg dose
PLACEBO_COMPARATOR: placebo; Placebo to match once daily	Drug: placebo; Placebo to match

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: December 21, 2011
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (ESTIMATE): January 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 21, 2016
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Diabetic Macular Edema
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Diabetic Retinopathy; Macular Edema; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phospholipase A2 Inhibitors; Darapladib
• Other Study ID Numbers: 115403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 115403
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register