Preclinical Development
The potency and selectivity of SLx-2101 has been
characterized in a number of preclinical models.
Several head-to-head pre-clinical efficacy
studies
of erectile dysfunction have been
conducted with SLx-2101 against sildenafil,
vardenafil, and tadalafil.
SLx-2101 was clearly superior to the responses
from sildenafil and tadalafil when assessing
response and superior to all three comparator
compounds when assessing duration of action.
Clinical Development
The Phase 1 study (N=40)
established safety and tolerability in healthy
volunteers and the extended duration of action.
The PK indicated that clinical activity could be
expected for at least 48 hours in ED patients and
even in this initial study extended duration of
action was established in endothelial function
using measures of peripheral arterial tone and
erectile function.
A single center repeat dose
study (7 days) and a Phase 2a study in erectile
dysfunction (ED) have been completed.
Repeat Dose Study
The repeat dose study
(N=48) is a
placebo controlled, randomized, double blind
study composed of three dose groups (5,10, and
20 mg).
Safety, PK and plasma levels of SLx-2101
and its M1 metabolite were monitored and
endothelial function was measured using the
Endo-PAT 2000™.
Interim results from this study have confirmed the initial
safety and tolerability seen in the Phase 1a
study. Notably the PK studies have shown no
evidence of accumulation with preliminary
Endo-PAT data showing improvement in endothelial
function after single and multiple doses of
SLx-2101.
Phase 2a ED Study
The Phase 2a study (N=40)
is a placebo controlled, randomized,
double blind, cross-over study
with five single dose groups (5, 10, 20,
and 40 mg). The patients in this study have well
established ED and are known to respond to the
marketed PDE-5 inhibitors. Safety and PK
(SLx-2101 and its M1 metabolite) were
monitored. Erectile response was assessed using
Rigiscan™ measure in response to visual sexual
stimulation (VSS).
Interim results have confirmed the initial safety and
tolerability and the Rigiscan™ data has shown
significant erectile activity in comparison to
placebo at 48 hours post-dose. This activity has
been seen at all doses tested.
The clinical experience of SLx-2101 to date
establishes the PK range of the PDE5 inhibitor
as well as demonstrating
efficacy in established models of endothelial
function (peripheral arterial tone and erectile
function). Additional Phase 2a studies in
hypertension and in Raynaud's disease are underway, and preliminary results are very promising. |
