NicOx
S.A. (Euronext Paris: COX) announced positive top-line results from a
118 patient Ambulatory Blood Pressure Monitoring (ABPM) trial (the 111
study), which compared the 24-hour blood pressure profile of escalating
doses of naproxcinod and naproxen in osteoarthritis (OA) patients with
controlled hypertension. The primary ABPM parameter was the mean 24-hour
ambulatory systolic blood pressure (SBP) measured by ABPM over the whole
study period and naproxcinod showed a statistically significant decrease in
SBP of 3.8 mmHg (p=0.011) compared to naproxen. Furthermore, in contrast to
naproxen, naproxcinod reduced the mean 24-hour SBP and diastolic blood
pressure (Buy generic acomplia DBP) from baseline at every dose comparison. Good safety and
tolerability were shown by all naproxcinod doses. NicOx plans to provide
further details of the results at a leading cardiology conference in 2009.
Naproxcinod is the first investigational drug in the new
Cyclooxygenase-Inhibiting Nitric Oxide-Donator (CINOD) class of
anti-inflammatory agents, which is nearing the end of phase 3 clinical
development for the treatment of the signs and symptoms of osteoarthritis,
with the submission of a New Drug Application (NDA) with the US Food and
Drug Administration (FDA) projected for mid-2009. NicOx expects to have the
results of a second large ABPM study in patients with hypertension and OA
(112) before the end of 2008, in addition to the results of the remaining
pivotal phase 3 trial in hip OA (303).
COX-2 inhibitors and traditional non-steroidal anti-inflammatory drugs
(NSAIDs), such as naproxen and ibuprofen, are widely used as symptomatic
treatments for OA. However, they can cause new episodes of high blood
pressure and destabilize previously controlled hypertensive patients, which
is a particular concern in the OA population where approximately 50% of
patients are estimated to be hypertensive.
"These impressive results suggest that naproxcinod could represent a
valuable treatment alternative for osteoarthritis patients," said Raymond
Townsend, Professor of Medicine at the University of Pennsylvania, who
advised NicOx on the design and analysis of the study. "The hypertensive
side effects of COX-2 inhibitors and traditional NSAIDs are a serious
medical issue and there is a clear need for a new drug with no detrimental
effect on blood pressure. These ABPM data have been obtained in a relevant
population of chronically treated osteoarthritis patients with many
cardiovascular risk factors and clearly show a consistent beneficial effect
on blood pressure for naproxcinod across the dose range, in contrast to
naproxen. In addition, the use of the ABPM technique gives them
considerable weight, as it is widely recognized as the gold standard method
for assessing the blood pressure profile of new drugs."
The 111 study design and results
In the study, 118 patients were randomized on a 1:1 basis to receive
naproxcinod or naproxen, with escalating doses every three weeks. The trial
included three doses of naproxcinod (375 mg bid, 750 mg bid and a
supra-therapeutic dose of 1125 mg bid), which were compared to naproxen
(250, 500 and 750 mg bid). 24-hour blood pressure monitoring was conducted
at baseline and at the end of each three-week dose escalation (i.e. at the
end of week 3, 6 and 9), using an FDA validated, ABPM device.
The primary objective of the study was to characterize the 24-hour
arterial blood pressure profile of the three doses of naproxcinod, as
measured by ABPM after each dose, compared to naproxen. At all time points,
naproxcinod showed a decrease in the mean 24-hour SBP and DBP from baseline
in contrast to naproxen. In terms of the overall treatment effect, as an
average over week 3, 6 and 9, naproxen raised SBP by 1.5 mmHg from
baseline, while naproxcinod lowered it by 2.3 mmHg, resulting in a
difference between the two treatments of 3.8 mmHg (p=0.011) in favor of
naproxcinod.
Michele Garufi, Chairman and CEO of NicOx, commented: "These excellent
results are an important addition to the consistent data we are
accumulating on naproxcinod’s potentially non-detrimental blood pressure
profile and its clear differentiation from naproxen. We are confident that
naproxcinod’s potential will be confirmed by the further clinical results
expected in the coming months."
The three doses of naproxcinod showed good general safety and
tolerability. In the naproxcinod arm 32 patients (54.2%) experienced one or
more adverse events, compared to 38 patients (64.4%) in the naproxen arm.
There were no serious adverse events in the naproxcinod arm.
Additional note on study design: The 111 study was a 12-week
pharmacodynamic ABPM trial (with 9 weeks of active treatment), with a
double-blind, parallel group design, in which 118 OA patients with
controlled hypertension were enrolled at 30 clinical sites in the United
States. Eligible patients were 40 years and older and had been suffering
from osteoarthritis for at least three months, with at least one hip or
knee involved. In addition to OA, all patients were diagnosed with
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