Purchase this article with an account.
Veronica Ruz, Javier Moreno-Montañés, Belén Sadaba, Victoria González, Ana Isabel Jiménez; Phase I Study With A New siRNA: SYL040012. Tolerance And Effect On Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2011;52(14):223.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To evaluate the safety of SYL040012, a new topical treatment for ocular hypertension and open angle glaucoma. To explore the effect on intraocular pressure (IOP) of different doses of SYL040012 in healthy volunteers.
SYL040012 is a new chemical entity targeting beta 2 adrenergic receptors (ADRB2) involved in intraocular pressure (IOP) regulation. SYL040012 siRNA targeting ADRB2 were administered as eyedrops in saline solution to 30 healthy voluntaries with normal IOP at two different doses (clinical trial Phase I). The study was set out in two periods; the first period (n = 6 healthy volunteers) is an initial evaluation of safety using a single dose of product; the second period (n = 24 healthy volunteers) is in multiple ascending doses (a single daily administration in one of the eyes during 7 days). For both periods each volunteer was his own IOP control. The eye to receive administration was randomized. Safety evaluation and IOP measurement were performed on both eyes. The ophthalmologist evaluating safety was blind regarding drug administration. The second period began once security and pharmacokinetics of the first period were evaluated.
Local tolerance was excellent. No modifications of the ocular surface or iris were detected. The analytical results at final examination did not show differences from those observed during selection. There were statistical differences between area under curve (AUC) of IOP curves on day four with respect to selection day curve (12% decrease) in all volunteers administered with the low level dose of SYL040012 during seven days. Five of them (with an average basal value of IOP higher than the mean value for the whole group) showed reduction higher than 15%. SYL040012 was not detected in blood.
The Phase I clinical trial for SYL040012 was completed in 30 healthy volunteers. SYL040012 showed excellent local and systemic tolerance after single and multiple administrations to subjects.
Clinical Trial: :
This PDF is available to Subscribers Only