Naproxcinod

Source: Wikipedia, the free encyclopedia.

Naproxcinod
Clinical data
Other namesAZD-3582, HCT-3012
ATC code
Identifiers
  • 4-nitrooxybutyl (2S)-2-(6-methoxynaphthalen-2-yl)propanoate
JSmol)
  • C[C@@H](C1=CC2=C(C=C1)C=C(C=C2)OC)C(=O)OCCCCO[N+](=O)[O-]
  • InChI=1S/C18H21NO6/c1-13(18(20)24-9-3-4-10-25-19(21)22)14-5-6-16-12-17(23-2)8-7-15(16)11-14/h5-8,11-13H,3-4,9-10H2,1-2H3/t13-/m0/s1 ☒N
  • Key:AKFJWRDCWYYTIG-ZDUSSCGKSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Naproxcinod (nitronaproxen) is a

cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.[1][2]

In December 2006,

U.S. Food and Drug Administration determined that further clinical trials would be needed to obtain approval.[4]

Current situation in pain treatment

Many people are currently relying on traditional NSAIDs and

heart attacks.[5] Therefore, there is an unmet need for safer medications. This need is particularly acute among patients with high cardiovascular risk like hypertension which represents 50% of osteoarthritis sufferers.[citation needed
]

Indications

Three phase III clinical trials led by NicOx have shown that naproxcinod was effective to treat pain against knee osteoarthritis[6][7][8] and hip osteoarthritis.[9] A phase II study showed no significant differences in efficacy between naproxcinod and the COX-2 inhibitor rofecoxib in the treatment of pain.[10]

In osteoarthritis, a 750 mg dose is equipotent to 500 mg of naproxen for the treatment of inflammation but with the added benefit of attenuating the cardiovascular effects traditionally associated with NSAIDs.[11]

In July 2010 the FDA decided not to approve naproxcinod.[4]

Mechanism of action

Naproxcinoid is metabolized to naproxen and a nitric oxide donating

vasodilatory and platelet-inhibitory actions as well as the inhibition of vascular smooth muscle proliferation that serves to maintain normal vascular tone.[11]

Safety profile

Blood pressure profile

According to some experts[

mmHg after patients took naproxcinod (375 mg or 750 mg twice daily) for six weeks. These effects were especially pronounced in hypertensive populations.[10][12]

Clinical relevance of small increase in blood pressure

During a

U.S. Food and Drug Administration (FDA) COX-2 advisory committee meeting, doctors have underlined the important role of small increase in blood pressure.[13] They cited the CAMELOT trial which has concluded that even a small decrease in systolic blood pressure of 5 mmHg could lead to a reduction of 31% in cardiovascular events.[14] Clinical studies about rofecoxib have shown that this drug increases the systolic blood pressure.[15]

A 2005 analysis shows that a blood pressure decrease of 3.1 mmHG could avoid over 30,000 deaths from stroke and 2,000 deaths from

US$ in direct health care cost savings.[16]

Gastrointestinal safety

NSAIDs have also been associated with

gastroduodenal mucosa,[17][18] but a 2009 review has found only a slight and possibly not clinically relevant reduction of gastrointestinal side-effects.[19][20]

Contraindications and adverse effects

Similarly to NSAIDs, adverse effects of naproxcinod include gastrointestinal bleedings.[19][20]

Commercialization

Naproxcinod completed a phase III study needed for a New Drug Application (NDA). As a result, Nicox submitted its project to the FDA in September 2009.[21] In July 2010, the FDA decided not to approve naproxcinod without further clinical trials.[4] Nicox submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) in December 2009.[22] Nicox and Fera Pharmaceuticals announced in November 2015 that they had entered into a license agreement for the development and commercialization of naproxcinod in the United States.[23]

See also

References

  1. S2CID 3231846
    .
  2. PMID 16613570
    .
  3. ^ Special Report: 10 Promising Treatments for World's Biggest Health Threats, By Charles Q. Choi. 2006
  4. ^ a b c NicOx Shares Plummet as FDA Says Osteoarthritis Drug Not Ready for Approval
  5. S2CID 39981292
    .
  6. ^ "NicOx Announces Top-Line Results From Naproxcinod 52-Week 301 Safety Extension". 24 July 2008. Retrieved 2 February 2010.
  7. ^ Clinical trial number NCT00542555 for "Analgesic Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Knee" at ClinicalTrials.gov
  8. ^ Clinical trial number NCT00504127 for "Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Knee" at ClinicalTrials.gov
  9. ^ Clinical trial number NCT00541489 for "Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Hip" at ClinicalTrials.gov
  10. ^
    PMID 19411388
    .
  11. ^
    PMID 19733721
    .
  12. PMID 19230986
    .
  13. ^ "Analysis of FDA COX-2 Advisory Committee Meeting" (PDF). 2005. p. 21.
  14. PMID 15536108
    .
  15. PMID 12683425
    .
  16. S2CID 19825259
    .
  17. S2CID 8025524
    .
  18. PMID 14570719
    .
  19. ^
    S2CID 70711735
    .
  20. ^ a b Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2010
  21. ^ Michelson M (25 September 2009). "NicOx submits naproxcinod application to FDA". Reuters. Retrieved 3 February 2010.
  22. ^ "MAA for naproxcinod submitted to EMEA through centralized procedure". NewsMedical.net. 22 December 2009. Retrieved 2 February 2010. [dead link]
  23. ^ "Fera Pharmaceuticals - Press Releases". www.ferapharma.com. Retrieved 20 April 2016.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Naproxcinod&oldid=1187504828"