An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee

Pain

Volumn 153, Issue 9, 2012, Pages 1837-1846

  Huggins, John P ^a   Smart, Trevor S ^a   Langman, Stephen ^a   Taylor, Louise ^a   Young, Tim ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Crossover design; FAAH1; Osteoarthritis; Pain; PF 04457845; Translation

Indexed keywords

ENDOCANNABINOID; FATTY ACID AMIDASE; FATTY ACID AMIDASE INHIBITOR; NAPROXEN; PF 04457845; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; ANALGESIA; ARTICLE; BACKACHE; BLOOD SAMPLING; BODY MASS; CONSTIPATION; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG INDICATION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; ENZYME ACTIVITY; ENZYME SUBSTRATE; FATIGUE; FEMALE; HUMAN; KNEE OSTEOARTHRITIS; KNEE PAIN; MAJOR CLINICAL STUDY; MALE; NEUROMODULATION; OUTCOME ASSESSMENT; PAIN ASSESSMENT; PATIENT CARE; PRACTICE GUIDELINE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; TREATMENT DURATION; UPPER RESPIRATORY TRACT INFECTION;

ADULT; AGED; AMIDOHYDROLASES; ANALGESICS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARTHRALGIA; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; ENDOCANNABINOIDS; FEMALE; HUMANS; KNEE JOINT; MALE; MEDICAL FUTILITY; MIDDLE AGED; NAPROXEN; OSTEOARTHRITIS, KNEE; PAIN MEASUREMENT; PYRIDAZINES; SINGLE-BLIND METHOD; TREATMENT OUTCOME; UREA;

EID: 84864577250     PISSN: 03043959     EISSN: 18726623     Source Type: Journal    
DOI: 10.1016/j.pain.2012.04.020     Document Type: Article

References (59)

1. D.I. Abrams, C.A. Jay, S.B. Shade, H. Vizoso, H. Reda, S. Press, M.E. Kelly, M.C. Rowbotham, and K.L. Petersen Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial Neurology 68 2007 515 521
2. P. Adamczyk, A. Golda, A.C. McCreary, M. Filip, and E. Przegalinski Activation of endocannabinoid transmission induces antidepressant-like effects in rats J Physiol Pharmacol 59 2008 217 228
3. K. Ahn, D.S. Johnson, and B.F. Cravatt Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders Expert Opin Drug Discov 4 2009 763 784
4. K. Ahn, D.S. Johnson, M. Mileni, D. Beidler, J.Z. Long, M.K. McKinney, E. Weerapana, N. Sadagopan, M. Liimatta, S.E. Smith, S. Lazerwith, C. Stiff, S. Kamtekar, K. Bhattacharya, Y. Zhang, S. Swaney, K. Van Becelaere, R.C. Stevens, and B.F. Cravatt Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain Chem Biol 16 2009 411 420
5. K. Ahn, M.K. McKinney, and B.F. Cravatt Enzymatic pathways that regulate endocannabinoid signaling in the nervous system Chem Rev 108 2008 1687 1707
6. K. Ahn, S.E. Smith, M.B. Liimatta, D. Beidler, N. Sadagopan, D.T. Dudley, T. Young, P. Wren, Y. Zhang, S. Swaney, K. Van Becelaere, J.L. Blankman, D.K. Nomura, S.N. Bhattachar, C. Stiff, T.K. Nomanbhoy, E. Weerapana, D.S. Johnson, and B.F. Cravatt Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective FAAH inhibitor that reduces inflammatory and noninflammatory pain J Pharmacol Exp Ther 338 2011 114 124
7. R.D. Altman, M.C. Hochberg, R.W. Moskowitcz, and T.J. Schnitzer Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines Arthritis Rheum 43 2000 1905 1915
8. N. Bellamy Pain assessment in osteoarthritis: experience with the WOMAC Osteoarthritis Index Semin Arthritis Rheum 18 1989 14 17
9. N. Bellamy, W.W. Buchanan, C.H. Goldsmith, J. Campbell, and L.W. Stitt Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee J Rheumatol 15 1988 1833 1840
10. J.S. Berman, C. Symonds, and R. Birch Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial PAIN® 112 2004 299 306
11. D.L. Boger, H. Miyauchi, W. Du, C. Hardouin, R.A. Fecik, H. Cheng, I. Hwang, M.P. Hedrick, D. Leung, O. Acevedo, C.R. Guimaraes, W.L. Jorgensen, and B.F. Cravatt Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics J Med Chem 48 2005 1849 1856
12. L. Chang, L. Luo, J.A. Palmer, S. Sutton, S.J. Wilson, A.J. Barbier, J.G. Breitenbucher, S.R. Chaplan, and M. Webb Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms Br J Pharmacol 148 2006 102 113
13. Y. Cheng, and S.A. Hitchcock Targeting cannabinoid agonists for inflammatory and neuropathic pain Expert Opin Investig Drugs 16 2007 951 965
14. B. Costa, I. Bettoni, S. Petrosino, F. Comelli, G. Giagnoni, and V. Di Marzo The dual fatty acid amide hydrolase/TRPV1 blocker, N-arachidonoyl- serotonin, relieves carrageenan-induced inflammation and hyperalgesia in mice Pharmacol Res 61 2010 537 546
15. B. Costa, F. Comelli, I. Bettoni, M. Colleoni, and G. Giagnoni The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors PAIN® 139 2008 541 550
16. B.F. Cravatt, K. Demarest, M.P. Patricelli, M.H. Bracey, D.K. Giang, B.R. Martin, and A.H. Lichtman Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase Proc Natl Acad Sci USA 98 2001 9371 9376
17. B.F. Cravatt, A. Saghatelian, E.G. Hawkins, A.B. Clement, M.H. Bracey, and A.H. Lichtman Functional disassociation of the central and peripheral fatty acid amide signaling systems Proc Natl Acad Sci USA 101 2004 10821 10826
18. R.J. Ellis, W. Toperoff, F. Vaida, G. van den Brande, J. Gonzales, B. Gouaux, H. Bentley, and J.H. Atkinson Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial Neuropsychopharmacology 34 2009 672 680
19. G. Gobbi, F.R. Bambico, R. Mangieri, M. Bortolato, P. Campolongo, M. Solinas, T. Cassano, M.G. Morgese, G. Debonnel, A. Duranti, A. Tontini, G. Tarzia, M. Mor, V. Trezza, S.R. Goldberg, V. Cuomo, and D. Piomelli Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis Proc Natl Acad Sci USA 102 2005 18620 18625
20. A.R. Hariri, A. Gorka, L.W. Hyde, M. Kimak, I. Halder, F. Ducci, R.E. Ferrell, D. Goldman, and S.B. Manuck Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function Biol Psychiatry 66 2009 9 16
21. S. Holt, F. Comelli, B. Costa, and C.J. Fowler Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw inflammation in pentobarbital-treated mice. comparison with indomethacin and possible involvement of cannabinoid receptors Br J Pharmacol 146 2005 467 476
22. R.D. Hosking, and J.P. Zajicek Therapeutic potential of cannabis in pain medicine Br J Anaesth 101 2008 59 68
23. A.C. Howlett, F. Barth, T.I. Bonner, G. Cabral, P. Casellas, W.A. Devane, C.C. Felder, M. Herkenham, K. Mackie, B.R. Martin, R. Mechoulam, and R.G. Pertwee International Union of Pharmacology. XXVII. Classification of cannabinoid receptors Pharmacol Rev 54 2002 161 202
24. S. Huitron-Resendiz, M. Sanchez-Alavez, D.N. Wills, B.F. Cravatt, and S.J. Henriksen Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolase Sleep 27 2004 857 865
25. A. Jayamanne, R. Greenwood, V.A. Mitchell, S. Aslan, D. Piomelli, and C.W. Vaughan Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models Br J Pharmacol 147 2006 281 288
26. M. Karst, K. Salim, S. Burstein, I. Conrad, L. Hoy, and U. Schneider Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial JAMA 290 2003 1757 1762
27. S. Kathuria, S. Gaetani, D. Fegley, F. Valino, A. Duranti, A. Tontini, M. Mor, G. Tarzia, G. La Rana, A. Calignano, A. Giustino, M. Tattoli, M. Palmery, V. Cuomo, and D. Piomelli Modulation of anxiety through blockade of anandamide hydrolysis Nat Med 9 2003 76 81
28. J.H. Kellgren, and J.S. Lawrence Radiological assessment of osteo-arthrosis Ann Rheum Dis 16 1957 494 502
29. M.G. Kenward, and J.H. Roger The use of baseline covariates in crossover studies Biostatistics 11 2010 1 17
30. S.G. Kinsey, J.Z. Long, S.T. O'Neal, R.A. Abdullah, J.L. Poklis, D.L. Boger, B.F. Cravatt, and A.H. Lichtman Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain J Pharmacol Exp Ther 330 2009 902 910
31. A.J. Kivitz, R.W. Moskowitz, E. Woods, R.C. Hubbard, K.M. Verburg, J.B. Lefkowith, and G.S. Geis Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip J Int Med Res 29 2001 467 479
32. G.L. Li, H. Winter, R. Arends, G.W. Jay, V. Le, T. Young, and J.P. Huggins Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects Br J Clin Pharmacol 73 2012 706 716
33. A.H. Lichtman, D. Leung, C.C. Shelton, A. Saghatelian, C. Hardouin, D.L. Boger, and B.F. Cravatt Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity J Pharmacol Exp Ther 311 2004 441 448
34. S. Maione, L. De Petrocellis, V. de Novellis, A.S. Moriello, S. Petrosino, E. Palazzo, F.S. Rossi, D.F. Woodward, and V. Di Marzo Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors Br J Pharmacol 150 2007 766 781
35. W. Makarowski, W.W. Zhao, T. Bevirt, and D.P. Recker Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen Osteoarthritis Cartilage 10 2002 290 296
36. E. Martín-Sánchez, T.A. Furukawa, J. Taylor, and J.L.R. Martin Systematic review and meta-analysis of cannabis treatment for chronic pain Pain Med 10 2009 1353 1368
37. F. Massa, G. Marsicano, H. Hermann, A. Cannich, K. Monory, B.F. Cravatt, G.L. Ferri, A. Sibaev, M. Storr, and B. Lutz The endogenous cannabinoid system protects against colonic inflammation J Clin Invest 113 2004 1202 1209
38. P. Movahed, B.A. Jönsson, B. Birnir, J.A. Wingstrand, T.D. Jorgensen, A. Ermund, O. Sterner, P.M. Zygmunt, and E.D. Högestätt Endogenous unsaturated C18 N-acylethanolamines are vanilloid receptor (TRPV1) agonists J Biol Chem 280 2005 38496 38504
39. P.S. Naidu, S.G. Kinsey, T.L. Guo, B.F. Cravatt, and A.H. Lichtman Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase J Pharmacol Exp Ther 334 2010 182 190
40. P.S. Naidu, S.A. Varvel, K. Ahn, B.F. Cravatt, B.R. Martin, and A.H. Lichtman Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality Psychopharmacology 192 2007 61 70
41. S. Petrosino, and V. Di Marzo FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels Curr Opin Investig Drugs 11 2010 51 62
42. K. Posner, M.A. Oquendo, M. Gould, B. Stanley, and M. Davies Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants Am J Psychiatry 164 2007 1035 1043
43. A.S.C. Rice Should cannabinoids be used as analgesics for neuropathic pain? Nat Rev Neurol 4 2008 654 655
44. A.S.C. Rice, I. Lever, and R. Zarnegar Cannabinoids and analgesia, with special reference to neuropathic pain H.J. McQuay, E. Kalso, R.A. Moore, Systematic reviews in pain research: methodology refined 2008 IASP Press Seattle 233 246
45. D.J. Rog, T.J. Nurmikko, T. Friede, and C.A. Young Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis Neurology 65 2005 812 819
46. A. Romero-Sandoval, and J.C. Eisenach Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision Anesthesiology 106 2007 787 794
47. R. Russo, J. Loverme, G. La Rana, T.R. Compton, J. Parrott, A. Duranti, A. Tontini, M. Mor, G. Tarzia, A. Calignano, and D. Piomelli The fatty acid amide hydrolase inhibitor URB597 (cyclohexylcarbamic acid 3′- carbamoylbiphenyl-3-yl ester) reduces neuropathic pain after oral administration in mice J Pharmacol Exp Ther 322 2007 236 242
48. K. Salim, U. Schneider, S. Burstein, L. Hoy, and M. Karst Pain measurements and side effect profile of the novel cannabinoid ajulemic acid Neuropharmacology 48 2005 1164 1171
49. T.J. Schnitzer, A.J. Kivitz, R.S. Lipetz, N. Sanders, and A. Hee Comparison of the COX-inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of osteoarthritis of the knee Arthritis Rheum 53 2005 827 837
50. N. Schuelert, M.P. Johnson, J.L. Oskins, K. Jassal, M.G. Chambers, and J.J. McDougall Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis PAIN® 152 2011 975 981
51. K.B. Svendsen, T.S. Jensen, and F.W. Bach Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial BMJ 329 2004 253 257
52. O. Svensson, M. Malmenas, L. Fajutrao, E.M. Roos, and L.S. Lohmander Greater reduction of knee than hip pain in osteoarthritis treated with naproxen, as evaluated by WOMAC and SF-36 Ann Rheum Dis 65 2006 781 784
53. A. Telleria-Diaz, M. Schmidt, S. Kreusch, A.K. Neubert, F. Schache, E. Vazquez, H. Vanegas, H.G. Schaible, and A. Ebersberger Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: involvement of prostaglandins and endocannabinoids PAIN® 148 2010 26 35
54. D.T. Wade, P. Makela, P. Robson, H. House, and C. Bateman Do cannabis-based medicinal extracts have general of specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients Mult Scler 10 2004 434 441
55. D.F. Woodward, R.W. Carling, C.L. Cornell, H.G. Fliri, J.L. Martos, S.N. Pettit, Y. Liang, and J.W. Wang The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products Pharmacol Ther 120 2008 71 80
56. J. Zajicek, P. Fox, and H. Sanders Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial Lancet 362 2003 1517 1526
57. J.P. Zajicek, H.P. Sanders, D.E. Wright, P.J. Vickery, W.M. Ingram, S.M. Reilly, A.J. Nunn, L.J. Teare, P.J. Fox, and A.J. Thompson Cannabinoids in Multiple Sclerosis (CAMS) study: safety and efficacy data for 12 months follow up J Neurol Neurosurg Psychiatry 76 2005 1664 1669
58. A.S. Zigmond, and R.P. Snaith The Hospital Anxiety and Depression Scale Acta Psychiatr Scand 67 1983 361 370
59. P.M. Zygmunt, J. Petersson, D.A. Andersson, H. Chuang, M. Sorgård, V. Di Marzo, D. Julius, and E.D. Högestätt Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide Nature 400 1999 452 457