Nitronaproxen [
AZD 3582,
HCT 3012,
naproxen nitroxybutylester,
NO-naproxen] is a
naproxen derivative with similar anti-inflammatory activity to the parent compound, but with less gastrointestinal toxicity. It is the first of a new class of
analgesic and anti-inflammatory drugs known as
cyclo-oxygenase-inhibiting
nitric oxide donators (CINODs), which are under development by
NicOx. The better gastrointestinal tolerability of
nitronaproxen appears to be due to its release of
nitric oxide (NO) and the consequent maintenance of tissue perfusion and integrity.
Nitronaproxen is in phase III clinical development for the treatment of
osteoarthritis and is available for licensing. AstraZeneca had been a worldwide licensee for
nitronaproxen and other CINODs. However, the results of phase II clinical trials of
nitronaproxen did not fulfill AstraZeneca's strategic commercial criteria for further investment and
NicOx reacquired rights following AstraZeneca's decision to discontinue its involvement in 2003.
NicOx was surprised by AstraZeneca's decision, and remained fully convinced of the potential of
nitronaproxen.
NicOx is seeking new partners for development of compounds of the CINOD class.
Nitronaproxen is in a phase III clinical trial for the treatment of
osteoarthritis (OA) of the knee. The 13-week trial completed enrolment of 820 patients from 120 clinical sites in the US in May 2006. The study is designed to confirm that
nitronaproxen is superior to placebo and is as effective as
naproxen in relieving signs and symptoms of OA. The study will also seek to show that
nitronaproxen has no adverse effect on blood pressure. An additional trial has begun that is employing ambulatory blood pressure monitoring to provide a description of the blood pressure effect of
nitronaproxen over a 24-hour period in hypertensive subjects. This US trial will enrol approximately 120 volunteers with stable
essential hypertension. The volunteers will not have
osteoarthritis but will be between the ages of 50 and 75 years (representative of the
osteoarthritis population). Results from both trials are expected in the fourth quarter of 2006. The phase II clinical programme for
nitronaproxen, which included 2709 patients in five separate clinical studies, showed that the
drug is a potent, safe
anti-inflammatory agent, with potential for improved cardiovascular safety over
NSAIDs and COX-2 selective
NSAIDs. An independent advisory board recommended further development of
nitronaproxen in the treatment of
osteoarthritis in 2004 based on an evaluation of the full results of the phase II clinical programme.A clinical study had begun in September 2004 at the University of Pennsylvania in patients with mild
essential hypertension, in which the effects of
nitronaproxen and
rofecoxib on arterial blood pressure would be compared. However,
rofecoxib was withdrawn worldwide on 1 October 2004. It is unclear if the trial was completed. The STAR Multinational Study Group has conducted a phase II gastrointestinal safety and efficacy study of
nitronaproxen versus
naproxen in 970 patients with
osteoarthritis at 80 sites in the following countries: Argentina, Brazil, Hungary, Mexico, Norway, Poland, South Africa and the UK. The study was completed in November 2002. AstraZeneca conducted a randomised, phase II trial evaluating the efficacy and safety of
nitronaproxen among 672 subjects with symptomatic
knee osteoarthritis. Results have been presented. Certain phase II trial data from 2003 had been somewhat disappointing. However, an underpowered trial and failures and deficiencies in a trial meant that it was not possible to draw conclusions from this data.