May 04, 2006 01:00 ET

NicOx initiates new trial to establish HCT 3012 as osteoarthritis treatment with beneficial blood pressure profile

Sophia Antipolis Cedex -- (MARKET WIRE) -- May 4, 2006 -- May 4, 2006. Sophia Antipolis, France.

NicOx S.A. (Eurolist: NICOX) today announced the initiation of a new clinical study designed to compare the 24-hour blood pressure profile of HCT 3012 and naproxen, using ambulatory blood pressure monitoring (ABPM). This study is expected to enroll approximately 120 volunteer subjects with stable essential hypertension (high blood pressure) at 15 clinical centers in the United States. The first subject has been enrolled and results are expected in the fourth quarter of 2006.

HCT 3012 is a novel, proprietary, nitric oxide-donating derivative of naproxen, which is currently in phase 3 clinical development for the treatment of the signs and symptoms of osteoarthritis. In addition to confirming the product's efficacy and overall safety in patients with osteoarthritis, the phase 3 program aims to demonstrate that HCT 3012 has no detrimental effect on blood pressure and for this reason standardized, controlled, office blood pressure measurements are being made in the ongoing phase 3 trial. The trial announced today is expected to provide key complementary data, by describing the blood pressure effect of HCT 3012 and naproxen over 24 hours in volunteer hypertensive subjects.

The anti-inflammatory agents currently used in the treatment of osteoarthritis are known to raise blood pressure and interfere with the treatment of hypertension. NicOx aims to develop HCT 3012 as the drug-of-choice for the symptomatic treatment of osteoarthritis by demonstrating that it has no detrimental effect on blood pressure.

Michele Garufi, Chairman and CEO of NicOx, commented: "Cardiovascular safety concerns have become a determining factor in influencing the prescription of anti-inflammatory agents and we believe that HCT 3012 will be a great commercial success if we demonstrate that it does not raise blood pressure. The trial announced today is expected to provide very important data, which together with that from our ongoing phase 3 efficacy study, should allow us to gain a clearer picture of the ability of nitric oxide donation to counteract the increased blood pressure observed with existing treatments for osteoarthritis."

Trial design and endpoints

This study is a double-blind, randomized, cross-over trial, which will enroll volunteer subjects with stable essential hypertension (see NOTE 1). Subjects will not have osteoarthritis but the trial will enroll people between the age of 50 and 75 to be representative of the osteoarthritis population. Subjects will be randomized to either one of two groups: approximately 60 will be treated with 750 mg of HCT 3012, twice-daily, for 14-days, followed by 500 mg of naproxen, twice-daily, for 14 days and a round a further 60 subjects will receive the compounds in the opposite order. Blood pressure measurements will be collected using an ABPM device (see NOTE 2).

The primary endpoint of the trial is the mean change from baseline for each active treatment period in the average 24 hour systolic blood pressure (SBP) recorded during a 24 hour ABPM. A number of secondary endpoints will follow a variety of additional blood pressure parameters, including diastolic blood pressure (DBP) and blood pressure values recorded during the day and night. The trial will also evaluate the general safety and tolerability of HCT 3012, compared to naproxen.

Non steroidal anti-inflammatory drugs (NSAIDs) represent the only established symptomatic treatment for the millions of patients who suffer from osteoarthritis worldwide. However, NSAIDs have the propensity to raise blood pressure and antagonize the blood pressure lowering effect of antihypertensive medications, to an extent that may increase the incidence of cardiovascular events. During 2005, the FDA requested that a warning should be added to the label of all marketed NSAIDs stressing that these drugs can lead to onset of new hypertension or wor sening of pre-existing hypertension and should be used with caution in patients with hypertension. Therefore, there is a true medical need for an anti-inflammatory agent with a neutral blood pressure or a slight blood pressure lowering effect, particularly among the 40% of osteoarthritis patients who are estimated to have coexisting hypertension. Furthermore, the recent clinical evidence suggesting a significant increase in cardiovascular risk among patients re ceiving COX-2 selective inhibitors has heightened the cardiovascular safety concerns surrounding the whole NSAID class.

HCT 3012 is a new chemical entity which is metabolized to yield naproxen (a currently marketed NSAID) and a nitric oxide-donating moiety. The sustained release of nitric oxide from this compound is expected to endow HCT 3012 with an improved blood pressure profile, compared to existing NSAIDs, due to the role of endothelial nitric oxide in controlling blood pressure. In line with this hypothesis, HCT 3012 appeared to show no unwanted increase in blood pressure in phase 2 trials, in contrast to NSAID comparators, and even a small reduction, an effect that was particularly marked in hypertensive patients.


Eligible subjects will be receiving stable antihypertensive treatment at screening. This is defined as no change in the type of drug they received, or no change in dose of 50% or more, due to disease worsening or lack of efficacy in the 3 months before screening. Antihypertensive treatment will be limited to a maximum of two different classes of anti-hypertensive agents, at no more than their recommended dose. People with uncontrolled hypertension will be excluded from the study, as will those using chronic analgesic or anti-inflammatory therapy, or which are expected to do so during the trial.


- Ambulatory blood pressure monitoring (ABPM) involves using a portable device to independently measure and record blood pressure at frequent intervals over a 24-hour period.

- Office blood pressure measurements (OBPM) are made by a health care professional during a subject's visit to their treatment center using standard equipment (i.e. a sphygmomanometer).

- Systolic blood pressure is the maximum pressure in the arteries when the heart is contracting, while diastolic pressure is the lowest pressure between heart beats.

NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development of nitric oxide-donating drugs to meet unmet medical needs. NicOx is targeting the therapeut ic areas of pain and inflammation and cardio-metabolic disease.

Resources are focused on two lead compounds, HCT 3012, in phase 3 development for the treatment of osteoarthritis, and NCX 4016, in phase 2 for Peripheral Arterial Obstructive Disease (PAOD). NicOx has strategic partnerships with some of the world's leading pharmaceutical companies, including Pfizer Inc. and Merck and Co., Inc.

NicOx S.A. is headquartered in Sophia-Antipolis, France, and is a public company listed on the Eurolist of Euronext Paris (segment: Next Economy).

The elements included in this communication may contain forward looking statements subject to certain risks and uncertainties. Actual results of the company may differ materially from those indicated in the forward-looking statements because of different risks factors described in the company's document de reference.


NicOx: Karl Hanks - Manager of Corporate Relations and Market Analysis - Tel +33 (0)497 15 22 03 -


Investors in the United States - Burns McClellan: Lisa Burns - / Laura Siino - - Tel +1 212 213 0006

Financial Dynamics: Jonathan Birt - Tel +1 212 850 56 34 - / Julia Phillips - Tel +44 (0)20 7831 3113 -

NicOx S.A.,

2455 route des Dolines, Espace Gaïa II, BP313, 06906 Sophia Antipolis cedex, France. Tel. +33 (0)4 9238 7020 - Fax +33 (0)4 9238 7030

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