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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01506895
First received: December 21, 2011
Last updated: March 7, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Retinopathy, Diabetic
Drug: darapladib
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in Visual Acuity as measured by ETDRS BCVA [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Mean change from baseline in SD-OCT after 3 months of treatment


Secondary Outcome Measures:
  • Changes in Retinal Anatomy [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Changes in retinal anatomy as assessed by fluorescein angiography and fundus photography and SD-OCT in the study eye

  • Safety and Tolerability as assessed by change from baseline in outcome measures [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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

  • Changes in Pharmacodynamic LP-PLA2 enzyme inhibition [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit

  • Peak plasma concentration (Cmax) of study drug [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Plasma Pharmacokinetic parameters of darapladib as data permit

  • Plasma concentration versus time curve (AUC) of study drug [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Plasma Pharmacokinetic parameters of darapladib as data permit


Enrollment: 54
Study Start Date: February 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01506895

Locations
Australia, New South Wales
GSK Investigational Site
Parramatta, New South Wales, Australia, 2150
GSK Investigational Site
Sydney, New South Wales, Australia, 2000
Australia, Victoria
GSK Investigational Site
East Melbourne, Victoria, Australia, 3002
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Denmark
GSK Investigational Site
Glostrup, Denmark
Germany
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51109
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48145
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Milano, Lombardia, Italy, 20157
GSK Investigational Site
Torino, Piemonte, Italy, 10122
GSK Investigational Site
Padova, Veneto, Italy, 35128
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
GSK Investigational Site
Rotterdam, Netherlands, 3011 BH
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01506895     History of Changes
Other Study ID Numbers: 115403
Study First Received: December 21, 2011
Last Updated: March 7, 2013
Health Authority: Italy: Coordinating site Local Competent Authority
European Union: European Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Australia: Human Research Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
Denmark: Danish Medicines Agency

Keywords provided by GlaxoSmithKline:
Diabetic Macular Edema

Additional relevant MeSH terms:
Diabetic Retinopathy
Edema
Macular Edema
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Signs and Symptoms
Macular Degeneration
Retinal Degeneration

ClinicalTrials.gov processed this record on April 21, 2014