SOPHIA ANTIPOLIS, France, Dec. 20 /PRNewswire/ -- NicOx S.A. (Eurolist: NICOX) today announced the initiation of the first phase 3 trial for HCT 3012 in patients with osteoarthritis of the knee. Patient screening has begun at the first wave of clinical centers and the majority of sites are expected to be initiated by the end of January 2006. The trial will involve approximately 120 clinical study sites and 820 patients in the United States. Results are anticipated in the fourth quarter of 2006. This represents the first study in the planned phase 3 program for HCT 3012. HCT 3012 is a novel, proprietary, nitric oxide-donating derivative of naproxen, which NicOx aims to develop as the drug-of-choice for osteoarthritis patients, particularly those with coexisting hypertension (high blood pressure).
The trial is designed to demonstrate that HCT 3012 is superior to placebo and as effective as naproxen in relieving the signs and symptoms of osteoarthritis, in addition to showing that HCT 3012 has no detrimental effect on blood pressure.
An estimated 43 million people suffer from arthritis in the United States, and the number is expected to rise to 59 million by 2020. Arthritic conditions account for the majority of the prescriptions for non-steroidal anti- inflammatory drugs (NSAIDs) and COX-2 inhibitors. These agents have recently been linked to an increased risk of cardiovascular adverse events, which may be partially due to their propensity to increase blood pressure and interfere with antihypertensive medication. Therefore, a true medical need exists for an NSAID with a neutral blood pressure-effect, especially among the 40% of osteoarthritis patients which are estimated to be hypertensive.
An additional trial is expected to start during the first half of 2006, which will employ ambulatory blood pressure monitoring (ABPM) to provide a description of the blood pressure profile of HCT 3012 and naproxen over a 24- hour period in hypertensive subjects.
Michele Garufi, Chairman and CEO of NicOx, commented: “We believe HCT 3012 has the potential to play a major role in the anti-inflammatory market. Our view is that HCT 3012 could become the reference drug for millions of osteoarthritis patients with hypertension if this phase 3 program is successful in confirming its lack of interference with blood pressure. Initiation of this trial represents an important step towards our goal of building NicOx into a fully integrated biopharmaceutical company and we intend to retain future marketing rights to HCT 3012 in specialist areas, in line with this goal.”
Trial design and endpoints
The study will be a 13-week, double-blind, placebo and naproxen-controlled trial, in patients with osteoarthritis of the knee. Eligible patients will be randomized to one of four treatment groups: HCT 3012 375 mg bid, HCT 3012 750 mg bid, naproxen 500 mg bid or placebo bid. The trial will involve around 120 clinical centers in the United States and approximately 205 patients will be enrolled per treatment group. Eligible patients will have a diagnosis of primary osteoarthritis of the knee of at least 3 months duration and must be current users of NSAIDs or acetaminophen (paracetamol) for their osteoarthritis pain (these analgesics will be withdrawn before treatment with study-drug). The study will enroll hypertensive and non-hypertensive patients, although patients with uncontrolled hypertension will be excluded.
HCT 3012 and placebo will be compared on three co-primary endpoints, based on the mean change between baseline and week-13 in the following scores: the WOMAC(TM) pain subscale, the WOMAC function subscale and patients’ overall rating of disease status, which are the standard end-points used to prove the efficacy of a drug for treating the signs and symptoms of osteoarthritis. A non-inferiority comparison of HCT 3012 and naproxen will be a secondary endpoint of the study, through duplicating the three co-primary endpoints. The trial has been powered to show statistical significance for both these comparisons (superiority of HCT 3012 versus placebo and non-inferiority of HCT 3012 versus naproxen).
Blood pressure monitoring and endpoints
Office blood pressure measurements (OBPM) will be performed at each visit (see NOTE 1). The blood pressure effect of HCT 3012, versus naproxen and placebo, will be assessed in the overall population and in the subpopulation of hypertensive patients.
Overall patient population: The primary blood pressure endpoint will be based on the difference between the systolic blood pressure measurements at baseline and the mean of the measurements at week 2, 6 and 13. A number of other endpoints will be based on the change in systolic and diastolic blood pressure from baseline, as well as the number of patients who initiate treatment with antihypertensive medication.
Hypertensive subpopulation: In this subgroup, endpoints will be based on the number of patients who need to switch or increase the dose of their ongoing antihypertensive treatment, in addition to the number of patients whose classification of hypertension changes from adequate to borderline or uncontrolled. There will also be a number of endpoints based on changes in systolic and diastolic blood pressure from baseline.
On December 15, 2005, the full results of the OASIS phase 2 trial were published in the journal Arthritis Care and Research T.J. Schnitzer et al., Volume 53, Issue 6, page 827-837. The OASIS trial demonstrated that HCT 3012 375 mg and 750 mg bid were superior to placebo (p<0.001) and non-inferior to rofecoxib 25 mg per day (p<0.001) in treating the signs and symptoms of osteoarthritis of the knee, as measured by the difference between the baseline WOMAC pain subscale scores and the mean at 4 and 6 weeks. Although naproxen 500 mg bid was not formally tested for efficacy, both doses of HCT 3012 appeared to be as effective as naproxen in reducing the WOMAC pain subscale score. Mean systolic blood pressure was also lower in the HCT 3012 treatment groups at the end of 6 weeks, compared to baseline, in contrast to no change with placebo and an increase with rofecoxib and naproxen.
Discussions with the FDA are continuing concerning the requirements for long-term safety data needed for the approval of HCT 3012, including any possible cardiovascular outcome study. NicOx will inform investors once the details of the entire program for obtaining marketing approval in the United States and Europe has been defined.
NicOx is conducting the phase 3 trial announced today with the assistance of PRA International, one of the world’s leading contract research organizations (CROs).
NOTE 1: Office blood pressure measurements (OBPM) will be made by a health care professional at each visit using standard equipment (i.e. a sphygmomanometer). 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. Systolic blood pressure is the maximum pressure in the arteries when the heart is contracting, while diastolic pressure is the lowest pressure between heartbeats.
NicOx (Bloomberg: COX: FP, Reuters: NCOX.LN) is a product-driven biopharmaceutical company dedicated to the development of nitric oxide- donating drugs to meet unmet medical needs. NicOx is targeting the therapeutic 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.
CONTACTS: NicOx: Karl Hanks Manager of Corporate Relations and Market Analysis Tel +33 (0)497 15 22 03 hanks@nicox.comhttp://www.nicox.com Investors in the United States - Burns McClellan: Lisa Burns lburns@burnsmc.com Laura Siino lsiino@burnsmc.com Tel +1 212 213 0006 Financial Dynamics: Jonathan Birt Tel +1 212 850 56 34 jbirt@fd-us.com Julia Phillips Tel +44 (0)20 7831 3113 julia.phillips@fd.com
NicOx S.A.
CONTACT: Karl Hanks, Manager of Corporate Relations and Market Analysis ofNicOx, +33-497-15-22-03, hanks@nicox.com; or Investors in the UnitedStates: Lisa Burns, lburns@burnsmc.com, or Laura Siino, lsiino@burnsmc.com,both of Burns McClellan, +1-212-213-0006; or Jonathan Birt,+1-212-850-5634, jbirt@fd-us.com, or Julia Phillips, +44-20-7831-3113,julia.phillips@fd.com, both of Financial Dynamics
Web site: http://www.nicox.com/
