Primary: efficacy, assessed by best-corrected visual acuity and SD-OCT of 1 eye (*study eye*). Secondary: retina anatomy of the study eye, safety and tolerability, PK, PD.Exploratory: Best-corrected visual acuity, SD-OCT and retina anatomy of the…
ID
Source
Brief title
Condition
- Eye disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Best Corrected Visual Acuity and SD-OCT2 centre subfield retinal thickness in
the study eye.
Secondary outcome
Changes in retinal anatomy of the study eye, safety and tolerability, PK, PD.
Background summary
Macular edema is a major cause of vision loss in diabetic patients, which may
occur at any stage of diabetic retinopathy. Sight-threatening diabetic macular
edema (DME) has been managed with laser photocoagulation, and with off-label
use of intravitreally administered medications such as anti-VEGF agents and
corticosteroids.
In 2011 intravitreal ranibizumab was approved in Europe as the first
pharmacologic therapy for DME. However, an unmet need persists driven by the
need for less burdensome treatment options that ideally can also provide
superior outcomes.
Darapladib is a novel, selective, orally active inhibitor of Lp-PLA2 currently
under clinical development. Pre-clinical observations suggest that inhibition
of Lp-PLA2, using a variety of Lp-PLA2 inhibitor compounds, may reduce
diabetes-induced central nervous system (CNS) vascular permeability, including
the retina.
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 objective
Primary: efficacy, assessed by best-corrected visual acuity and SD-OCT of 1 eye
(*study eye*).
Secondary: retina anatomy of the study eye, safety and tolerability, PK, PD.
Exploratory: Best-corrected visual acuity, SD-OCT and retina anatomy of the
other eye.
Study design
Multicenter randomized double blind phase II parallel group study.
Randomisation (2:1) to treatment with:
1. Darapladib 160 mg once daily.
2. Placebo.
Treatment duration 3 months.
Stratification according to visual acuity.
50-100 patients.
Interim analysis after 10 or 20 active subjects complete 3 months of treatment
with darapladib without rescue treatment.
Intervention
Treatment with darapladib or placebo.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: 6 visits and 1 phone call in approx. 19 weeks. Duration 1-4 h (1x 9 h
for serial PK samples).
6x routine blood tests ca. 70 ml in total. 1x serial PK sampling with 7 samples
in approx. 8 h.
Optional pharmacogenetic blood sample (1x 10 ml).
5x general ohthalmological examination, 6x SD-OCT test.
2x fundus photography.
Huis ter Heideweg 62
3705 LZ Zeist
NL
Huis ter Heideweg 62
3705 LZ Zeist
NL
Listed location countries
Age
Inclusion criteria
* Male and female patients 18 years or above with diabetic macular edema and central involvement.
* Confirmation of diagnosis in the study eye by fluorescein angiography.
* Retinal thickening > 330 microns for Heidelberg Spectralis and >310 for Zeiss Cirrus.
* Best corrected visual acuity score of 78-24 letters (Snellen equivalent ~20/32 to 20/320).
* Diabetes mellitus type 1 or 2.
* Safe contraception for women of childbearing potential.
Exclusion criteria
* Additional eye disease in the study eye that could compromise assessments.
* Active proliferative diabetic retinopathy in the study eye.
* Ischemic maculopathy (see protocol for details).
* History of choroidal neovascularization in the study eye, or current choroidal neovascularization in the fellow eye requiring treatment.
* Intraocular surgery or laser photocoagulation in the study eye within 3 months of dosing.
* Study eye: intravitreal ranibizumab within 90 days or or intraocular steroids within 180 days of dosing.
* Fellow eye: (expected need for) intravitreal bevacizumab during the study.
* Best-corrected visual acuity score by electronic ETDRS < 56 letters in the fellow eye at screening.
* Use of any systemically administered anti-angiogenic agent within 6 months of dosing.
* Uncontrolled intraocular pressure >22 mmHg in the study eye despite treatment.
* Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina.
* HbA1c >10% at screening.
* Severe asthma that is poorly controlled.
* Chronic administration of strong CYP3A4 inhibitors.
* History of or current chronic use of systemic steroids 30 days or less prior to screening.
* Breastfeeding, pregnancy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2011-002944-28-NL |
| CCMO | NL38878.018.11 |