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Tapentadol for Use in the Treatment of Fibromyalgia and Chronic Fatigue Syndrome

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Tapentadol for Use in the Treatment of Fibromyalgia and Chronic Fatigue Syndrome (19) TZZ _T (11) EP 2 845 625 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 11.03.2015 Bulletin 2015/11 A61P 25/04 (2006.01) A61K 9/20 (2006.01) A61K 31/137 (2006.01) (21) Application number: 13182985.5 (22) Date of filing: 04.09.2013 (84) Designated Contracting States: (72) Inventors: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • Schiene, Klaus GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO 41363 Jüchen (DE) PL PT RO RS SE SI SK SM TR •Bloms-Funke, Petra Designated Extension States: 52146 Würselen (DE) BA ME (74) Representative: Brosch, Oliver et al (71) Applicant: Grünenthal GmbH Kutzenberger Wolff & Partner 52078 Aachen (DE) Theodor-Heuss-Ring 23 50668 Köln (DE) (54) Tapentadol for use in the treatment of fibromyalgia and chronic fatigue syndrome (57) The invention relates to tapentadol for use in the treatment of fibromyalgia or chronic fatigue syndrome. EP 2 845 625 A1 Printed by Jouve, 75001 PARIS (FR) 1 EP 2 845 625 A1 2 Description base or as a salt or solvate. The production of the free base is known, for example, from EP-A 693 475. For the [0001] The invention relates to tapentadol for use in purposes of the present invention tapentadol includes (1 the treatment of fibromyalgia and chronic fatigue syn- R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-pro- drome. The treatment is effective for treating fibromyal- 5 pyl)-phenol as well as physiologically acceptable salts gia-related pain and fatigue. and solvates thereof, in particular (1 R,2R)-3-(3-dimeth- [0002] Fibromyalgia syndrome (FMS) is a chronic, ylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride. widespread musculoskeletal pain and fatigue disorder, [0009] The invention further relates to a medicament estimated to affect 2-4% of the population. FMS is char- containing tapentadol for use in the treatment of fibromy- acterized by a generalized heightened perception of sen- 10 algia or chronic fatigue syndrome. The medicament is sory stimuli. Patients with FMS display abnormalities in preferably in a solid medicinal form. Semisolid, liquid or pain perception in the form of both allodynia (pain with pasty medicinal forms are also possible. innocuous stimulation) and hyperalgesia (increased sen- [0010] In an embodiment, the invention relates to said sitivity to painful stimuli). The syndrome, as defined by medicament and its use in the treatment of fibromyalgia the American College of Rheumatology’s criteria, in-15 or chronic fatigue syndrome wherein tapentadol is for- volves the presence of pain for over 3 months duration mulated in an controlled release form. Controlled release in all four quadrants of the body, as well as along the forms of tapentadol are known. Such medicaments may spine. In addition, pain is elicited at 11 out of 18 "tender be particularly useful for treating chronic conditions. The points" upon palpation. In addition to muscle pain and controlled release of tapentadol can, for example, be fatigue, many patients commonly develop sleep and20 achieved by retardation by means of a matrix, a coating mood disorders (e.g., anxiety, depression). Patients also or release systems with an osmotic action cf. the respec- show a higher incidence of stress-related symptoms. tive formulaions in US 2005/0058706A which content is [0003] Chronicfatigue syndrome (CFS) isa debilitating hereby incorporated by reference. disorder characterized by profound tiredness or fatigue. [0011] Controlled release of tapentadol is possible Patients with CFS may become exhausted with only light 25 from formulations such as those for oral, rectal or percu- physical exertion, and must often function at a level of taneous administration. Preferably, the medicament is activity substantially lower than their capacity before the formulated for once-daily administration, for twice-daily onset of illness. In addition to the key defining character- administration (bid) or for thrice-daily administration, with istic of fatigue, CFS patients generally report various non- twice-daily administration (bid) being particularly pre- specific symptoms, including weakness, muscle aches 30 ferred. and pains, excessive sleep, malaise, fever, sore throat, [0012] In another embodiment, the invention relates to tender lymph nodes, impaired memory and/or mental said medicament and its use in the treatment of fibromy- concentration, insomnia, and depression. Like patients algia or chronic fatigue syndrome wherein tapentadol is with FMS, patients with CFS suffer from disordered formulated in an immediate release form. Immediate re- sleep, localized tenderness, and complaints of diffuse 35 lease forms of tapentadol are known and are commer- pain and fatigue. cially available under the tradename Palexia and Nucyn- [0004] Owing to their common symptomology, FMS ta. and CFS are thought to be related. However, they man- [0013] In another embodiment, the invention relates to ifestdifferent majorsymptoms. Whereas pain isthe major said medicament and its use in the treatment of fibromy- symptom reported by patients with FMS, fatigue is the 40 algia or chronic fatigue syndrome which is formulated for major symptom reported by patients with CFS. oral administration. Such formulations may contain suit- [0005] It is an object of the invention to provide a med- able excipients and additives such as, e.g. disintegrants, icament containing at least one pharmacologically active lubricants, binders, fillers, mould release agents, option- compound that is useful in the treatment of fibromyalgia ally solvents, flavourings, sugar, in particular carriers, and chronic fatigue syndrome and that preferably has 45 diluents, colorants, antioxidants, etc. Oral solutions are advantages over the medicaments known in prior art for known from US 2013/0022670A which content is hereby the treatment of FMS and CMS. incorporated by reference. [0006] This object has been achieved by the subject- [0014] Suitable for oral administration are medica- matter of the patent claims and the specification. ments and/ or preparations which are in the form of tab- [0007] The invention therefore relates to the use of tap- 50 lets, chewable tablets, dragees, capsules, granules, entadol, preferably contained in a medicament, for use drops, juices or syrups; suitable for parenteral, topical in the treatment of fibromyalgia or chronic fatigue syn- and inhalative administration are solutions, suspensions, drome. easily reconstituted dry preparations and sprays. A fur- [0008] Tapentadol, i.e. (1R,2R)-3-(3-dimethylamino- ther possibility is suppositories for use in the rectum. Use 1-ethyl-2-methyl-propyl)-phenol (CAS no. 175591-23-8), 55 in a depot in dissolved form, a carrier foil or a plaster, is a synthetic, centrally acting analgesic which is effective optionally with the addition of means to encourage pen- in the treatment of moderate to severe, acute or chronic etration of the skin, are examples of suitable percutane- pain. The compound can be used in the form of its free ous administration forms. 2 3 EP 2 845 625 A1 4 [0015] According to the invention, the medicament contains tapentadol in an amount of 0.001 to 99.999 % containing tapentadol can also present in pharmaceutical by weight, preferably 0.1 to 99.9 % by weight, more pref- forms that are adapted for other than oral administration erably 1.0 to 99.0 % by weight, even more preferably 2.5 routes (cf. US 2012/0225950A, and US 2012/0225951A to 80 % by weight, most preferably 5.0 to 50 % by weight which contents are hereby incorporated by reference). 5 and in particular 7.5 to 40 % by weight, based on the total [0016] Depending upon the formulation, such pharma- weight of the medicament, and preferably is formulated ceutical forms may contain suitable additives and/or ex- as tablets, capsules, pellets or granules. cipients. Suitable additives and/or excipients are all sub- [0022] In another preferred embodiment of the inven- stances for achieving generally known galenic formula- tion the medicament contains tapentadol having a con- tions. The selection of these excipients and the amounts 10 trolled release from a matrix, and which medicament is to be used depend upon the anticipated administration in a solid and/or pressed and/or film-coated medicinal route (e.g. orally, intravenously, intraperitoneally, intra- form and is formulated for oral administration, which med- dermally, intramusuclarly, intranasally, buccally or topi- icament contains tapentadol in an amount of 0.001 to cally.administration routes, or buccal, sublingual, trans- 99.999 % by weight, preferably 0.1 to 99.9 % by weight, mucosal, rectal, intralumbar, intraperitoneal, transder- 15 more preferably 1.0 to 99.0 % by weight, even more pref- mal, intravenous, intramuscular, intragluteal, intracuta- erably 2.5 to 80 % by weight, most preferably 5.0 to 50 neous and subcutaneous administration routes). % by weight and in particular 7.5 to 40 % by weight, based [0017] For suppositories, it is possible to use inter alia on the total weight of the medicament, and which medi- waxes or fatty acid esters and for parenteral means of cament has a total mass in the range of from 25 to 2,000 application, carriers, preservatives, suspension aids, etc. 20 mg, preferably 50 to 1,800 mg, more preferably 60 to [0018] Suitable physiologically acceptable salts of tap- 1,600 mg, even more preferably 70 to 1,400 mg, most entadol which can be used according to the invention preferably 80 to 1,200 mg and in particular 100 to 1,000 include salts of inorganic acids, such as e.g. hydrogen mg and preferably is formulated as tablets, capsules, pel- chloride, hydrogen bromide and sulfuric acid, and salts lets or granules. of organic acids, such as methanesulfonic acid, fumaric 25 [0023] For the purpose of the specification, fibromyal- acid, maleic acid, acetic acid, oxalic acid, succinic acid, gia or chronic fatigue syndrome shall include conditions malic acid, tartaric acid, mandelic acid, lactic acid, citric and symptoms that are associated with fibromyalgia or acid, glutaminic acid, acetylsalicylic acid, nicotinic acid, chronic fatigue syndrome, particularly pain due to fibro- aminobenzoic acid, a-lipoic acid, hippuric acid and as- myalgia and pain due to chronic fatigue syndrome.
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