A Phase 2 Clinical Study to Investigate Effects of Darapladib in Subjects With Diabetic Macular Edema
Primary Purpose
Retinopathy, Diabetic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
darapladib
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Retinopathy, Diabetic focused on measuring Diabetic Macular Edema
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
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
darapladib
placebo
Arm Description
darapladib dosed at 160 mg once daily
Placebo to match once daily
Outcomes
Primary Outcome Measures
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
Change from baseline in Spectral Domain Optical Coherance Tomography
Mean change from baseline in SD-OCT after 3 months of treatment
Secondary Outcome Measures
Changes in Retinal Anatomy
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
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
Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit
Peak plasma concentration (Cmax) of study drug
Plasma Pharmacokinetic parameters of darapladib as data permit
Plasma concentration versus time curve (AUC) of study drug
Plasma Pharmacokinetic parameters of darapladib as data permit
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01506895
Brief Title
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
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy, Diabetic
Keywords
Diabetic Macular Edema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
darapladib
Arm Type
Experimental
Arm Description
darapladib dosed at 160 mg once daily
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to match once daily
Intervention Type
Drug
Intervention Name(s)
darapladib
Intervention Description
Experimental compound 160 mg dose
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Placebo to match
Primary Outcome Measure Information:
Title
Change from baseline in Visual Acuity as measured by ETDRS BCVA
Description
Mean change from baseline in ETDRS Best Corrected Visual Acuity (BCVA) after 3 months of treatment
Time Frame
3 months
Title
Change from baseline in Spectral Domain Optical Coherance Tomography
Description
Mean change from baseline in SD-OCT after 3 months of treatment
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Changes in Retinal Anatomy
Description
Changes in retinal anatomy as assessed by fluorescein angiography and fundus photography and SD-OCT in the study eye
Time Frame
3 months
Title
Safety and Tolerability as assessed by change from baseline in outcome measures
Description
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
Time Frame
3 months
Title
Changes in Pharmacodynamic LP-PLA2 enzyme inhibition
Description
Changes over 3 months in the study of LP-PLA2 Enzyme inhibition as data permit
Time Frame
3 months
Title
Peak plasma concentration (Cmax) of study drug
Description
Plasma Pharmacokinetic parameters of darapladib as data permit
Time Frame
3 months
Title
Plasma concentration versus time curve (AUC) of study drug
Description
Plasma Pharmacokinetic parameters of darapladib as data permit
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Parramatta
State/Province
New South Wales
ZIP/Postal Code
2150
Country
Australia
Facility Name
GSK Investigational Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia
Facility Name
GSK Investigational Site
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
GSK Investigational Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
GSK Investigational Site
City
Glostrup
Country
Denmark
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
89075
Country
Germany
Facility Name
GSK Investigational Site
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
51109
Country
Germany
Facility Name
GSK Investigational Site
City
Muenster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48145
Country
Germany
Facility Name
GSK Investigational Site
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
Facility Name
GSK Investigational Site
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10122
Country
Italy
Facility Name
GSK Investigational Site
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
GSK Investigational Site
City
Rotterdam
ZIP/Postal Code
3011 BH
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
115403
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
A Phase 2 Clinical Study to Investigate Effects of Darapladib in Subjects With Diabetic Macular Edema
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