View Full Version : Naproxcinod In Hypertensive Patients With Osteoarthritis

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03-16-2008, 08:47 PM
NicOx S.A. (Euronext Paris: COX) announced the initiation of two large clinical pharmacology studies in the United States, which will assess the blood pressure profile of naproxcinod in comparison to ibuprofen and naproxen, using the Ambulatory Blood Pressure Monitoring (ABPM) technique. These separate studies, 12 and 16 weeks in duration, will together recruit a total of around 420 osteoarthritis patients with controlled hypertension and results are projected in Q4 2008. Naproxcinod is NicOx' lead investigational drug and the first compound in the COX-Inhibiting Nitric Oxide-Donating (CINOD) class of anti-inflammatory agents, which is currently in phase 3 clinical development for the treatment of the signs and symptoms of osteoarthritis, with results of the last two phase 3 studies anticipated in the second half of 2008.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as ibuprofen and naproxen, are commonly used by osteoarthritis patients to control their chronic pain, inflammation and stiffness and significantly improve quality of life for millions of people. However, these important products have the tendency to raise blood pressure to an extent that may increase the rate of serious cardiovascular adverse events (see NOTE 1).

Pascal Pfister MD, Chief Scientific Officer and Head of Research and Development at NicOx, said: "Our development program for naproxcinod aims to address the safety concerns surrounding anti-inflammatory agents and blood pressure, which represents a serious medical issue. Previous studies using the ABPM technique and Office Blood Pressure Measurements have suggested that naproxcinod may have an improved blood pressure profile compared to existing anti-inflammatory drugs, which would greatly facilitate its future adoption by physicians and patients. These two new studies will provide important data in a relevant population of chronically treated osteoarthritis patients and should add additional weight to the consistent data we are accumulating on naproxcinod's blood pressure profile."

The objectives of these new ABPM studies (see NOTE 2) are to provide important additional data on the 24-hour blood pressure profile of naproxcinod in chronically treated osteoarthritis patients, in comparison to commonly used Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). These data should complement the promising results of a 2-week ABPM study for naproxcinod in healthy volunteers with hypertension (the 104 study), which were presented at the American Heart Association (AHA) in November 2007 (see press release of November 7, 2007). They will also complement the Office Blood Pressure Measurements (OBPMs) being collected in each of the pivotal phase 3 osteoarthritis studies (including the completed 301 study and the ongoing 302 and 303 studies

Design of the 111 and 112 ABPM studies

-- The 111 study is a 12-week, phase 1, double-blind, parallel group, exploratory trial, where approximately 120 patients will be enrolled at around 30 clinical sites in the United States. Patients will have a minimum age of 40 and be diagnosed with controlled essential hypertension and osteoarthritis, with at least one hip or knee involved. After a one week screening period, patients will be randomized to one of two groups, which will receive increasing doses of either naproxcinod or naproxen at three week intervals. 24-hour blood pressure monitoring will be conducted at baseline and at the end of each three-week dose escalation, using an ABPM device (see NOTE 2).

-- The 112 study is a 16-week, phase 1, double-blind, parallel group, exploratory trial, where approximately 300 patients will be recruited at around 60 clinical sites in the United States. As in the 111 study, patients will be 40 years, or older, with osteoarthritis in at least one hip or knee and a diagnosis of controlled essential hypertension. Following a one week screening period, patients will be randomized to either one of five groups, which will receive 13 weeks of treatment with: naproxcinod 375 mg bid (twice-daily), naproxcinod 750 mg bid, naproxen 250 mg bid, naproxen 500 mg bid or ibuprofen 600 mg tid. At the end of the treatment period, all patients will receive placebo for 2 weeks. 24-hour blood pressure monitoring will be conducted at baseline and at the end of the 13-week treatment period. The primary objective of the study is to assess the mean change from baseline in the average 24-hour systolic blood pressure, as well as evaluating the general safety and tolerability of naproxcinod.

Staffan Stromberg, Vice President of Drug Development at NicOx, said: "We have chosen naproxen as the comparator in the pivotal phase 3 studies, due to its well established anti-inflammatory efficacy and its perception as the least risky of the existing NSAIDs in terms of blood pressure and cardiovascular safety. In the 112 study, we will also obtain long term 24-hour blood pressure comparisons between our first CINOD and ibuprofen, the most widely used NSAID."

NOTE 1: The biological mechanisms by which NSAIDs increase blood pressure are not well understood, although an increase in blood vessel constriction, interference with antihypertensive treatment and retaining dietary salt all seem to contribute. The extent of the increase is not fully defined, although there appears to be a variation between different products, with ibuprofen and the selective COX-2 inhibitors bringing about greater increases than non- selective drugs, such as naproxen. However, all existing products have been associated with some blood pressure increase. Both treated hypertensive patients and individuals with normal blood pressure appear to be affected and the dose and duration of administration also seems to be important, with hypertension occurring more frequently with chronic treatment.

NOTE 2: Ambulatory Blood Pressure Measurement (ABPM) involves using a portable device to independently measure and record blood pressure at frequent intervals over a 24-hour period with minimal disruption of a subject's daily activity. In these new studies, blood pressure measurements will be taken at 20-minute intervals between 6:00 am and 10:00 pm and every hour from 10:01 pm to 5:59 am.

NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development and future commercialization of investigational drugs for unmet medical needs. NicOx is applying its proprietary nitric oxide-donating technology to develop an internal portfolio of New Chemical Entities (NCEs) in the therapeutic areas of inflammatory and cardio-metabolic disease.

Resources are focused on the development of naproxcinod, a proprietary NCE and the first compound in the COX-Inhibiting Nitric Oxide-Donating (CINOD) class of anti-inflammatory agents, which is in phase 3 clinical studies for the treatment of the signs and symptoms of osteoarthritis, with final phase 3 results anticipated in 2008.

Beyond naproxcinod, NicOx has a pipeline containing multiple nitric oxide- donating NCEs, which are in development internally and with partners, including Pfizer Inc and Merck & Co., Inc., for the treatment of prevalent and underserved diseases, such as atherosclerosis, hypertension, glaucoma and Chronic Obstructive Pulmonary Disease (COPD).

NicOx S.A. is headquartered in France and is listed on the Euronext Paris Stock Exchange (Compartment B: Mid Caps).

This press release contains certain forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated in the forward-looking statements.

For a discussion of risks and uncertainties which could cause actual results, financial condition, performance or achievements of NicOx S.A. to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Document de Reference filed with the AMF, which is available on the AMF website (http://www.amf-france.org (http://www.amf-france.org/)) or on NicOx S.A.'s website (http://www.nicox.com (http://www.nicox.com/)).

NicOx S.A.
http://www.nicox.com (http://www.nicox.com/)