FrancophonIA/ELRC3.0 huggingface dataset:
English: ANNEX II
Slovenian: Priloga II
English: • The Committee considered the notification of the referral triggered by the United Kingdom under Article 29(4) of Council Directive 2001/83/EC.
Slovenian: • je Odbor upošteval obvestilo o napotitvenem postopku, ki ga je sprožilo Združeno kraljestvo v skladu s členom 29(4) Direktive Sveta 2001/83/ES;
English: The total programme comprised 18 completed studies and included almost 5000 patients.
Slovenian: Celotni program je obsegal 18 zaključenih študij in v njem je sodelovalo skoraj 5000 bolnikov.
English: Predictive value of the FEV1 data
Slovenian: Napovedna vrednost podatkov o FEV1
English: None of the submitted clinical trials were of such duration.
Slovenian: Nobeno od predloženih kliničnih preskušanj ni trajalo toliko časa.
English: SCIENTIFIC CONCLUSIONS AND GROUNDS FOR POSITIVE OPINION
Slovenian: Znanstveni zaključki in podlaga za pozitivno mnenje
English: • The Committee reviewed all available data submitted by the applicant to address the potential serious risk to public health, in particular the efficacy in respect of long-term asthma control.
Slovenian: • je Odbor pregledal vse razpoložljive podatke, ki jih je predložil predlagatelj, z namenom reševanja vprašanja morebitnega resnega tveganja za javno zdravje, zlasti učinkovitosti v zvezi z dolgoročnim obvladovanjem astme;
English: However, the Applicant has found no evidence to support such a view in the literature.
Slovenian: Vendar predlagatelj v literaturi ni našel dokazov, ki bi podprli to stališče.
English: These include two published studies which specifically recruited patients with a history of recent exacerbations and which were conducted over 6 to 12 months (Ind 2003; Verona 2003).
Slovenian: To vključuje dve objavljeni študiji, v katerih so sprejeli specifično bolnike z nedavnimi poslabšanji v anamnezi in ki sta trajali od 6 do 12 mesecev (Ind 2003; Verona 2003).
English: This hypothesis has in turn led to concerns regarding the duration of the Applicant's 8 to 12 week studies.
Slovenian: Ta hipoteza je nato povzročila pomisleke v zvezi s trajanjem predlagateljevih od 8- do 12-tedenskih študij.
English: Moreover it was proposed that “severe” exacerbations are the most discriminative exacerbations variable.
Slovenian: Poleg tega se je pojavila domneva, da so „huda“ poslabšanja najznačilnejša spremenljivka poslabšanj.
English: Across a broad range of endpoints such as discontinuation due to lack of efficacy, symptom-free days and nights and the amount of rescue medication, the size of effect seen is clinically important.
Slovenian: Pri številnih končnih točkah, kot so prenehanje zdravljenja zaradi pomanjkanja učinkovitosti, dnevi in noči brez simptomov ter količina reševalnih zdravil, je velikost opaženega učinka klinično pomembna.
English: It is a multidimensional concept incorporating symptoms, night time awakenings, use of rescue medication, lung function and activity limitation.
Slovenian: Je večdimenzionalen koncept, ki vključuje simptome, nočna prebujanja, uporabo reševalnih zdravil, delovanje pljuč in omejitve pri opravljanju dejavnosti.
English: These conclusions based on an indirect assessment of future exacerbation risk are consistent with and support those based on a direct observation of exacerbation rates during the clinical studies.
Slovenian: Ti zaključki, ki temeljijo na posredni oceni tveganja za poslabšanje v prihodnosti, so skladni s tistimi, ki temeljijo na neposredni oceni stopenj tveganja med kliničnimi študijami, in jih podpirajo.
English: Again a similar pattern was evident from the Applicant's own long-term study.
Slovenian: Podoben vzorec so opazili tudi v predlagateljevi dolgotrajni študiji.
English: However the exacerbations data were supported by the nocturnal symptoms and discontinuations due to lack of efficacy data.
Slovenian: Kljub temu so podatke o poslabšanjih podprli podatki o nočnih simptomih in prenehanjih zdravljenja zaradi pomanjkanja učinkovitosti.
English: • The Committee considered that the overall safety and efficacy have been sufficiently proven by the studies presented.
Slovenian: • je Odbor presodil, da predložene študije zadovoljivo dokazujejo splošno varnost in učinkovitost.
English: With regard to the suggestion that “severe” exacerbations are the optimal variable with which to examine potential differences in inhaled corticosteroid effect, the applicant commented that literature does not support this view.
Slovenian: V zvezi z domnevo, da so „huda“ poslabšanja optimalna spremenljivka, s katero bi raziskali morebitne razlike v učinku inhalacijskega kortikosteroida, je predlagatelj komentiral, da literatura tega stališča ne podpira.
English: The five pivotal Iffeza Phase III studies included approximately 2500 patients and the safety database includes over 1900 Iffeza-treated patients.
Slovenian: Pet ključnih študij III. faze z zdravilom Iffeza je vključevalo približno 2500 bolnikov, podatkovna zbirka o varnosti pa vključuje podatke o več kot 1900 bolnikih, zdravljenih z zdravilom Iffeza.
English: To distinguish a potential difference a study with a long duration e.g. 6-12 months is necessary.
Slovenian: Za odkritje morebitne razlike bi bila potrebna dolgotrajna študija, npr. od 6- do 12-mesečna.
English: The Applicant's own short- and long-term studies have demonstrated the same association between FEV1 and future exacerbation risk.
Slovenian: Predlagateljeve lastne kratko- in dolgotrajne študije so pokazale enako povezavo med FEV1 in tveganjem za poslabšanje v prihodnosti.
English: The magnitude of changes seen on a range of secondary endpoints helps to quantify the clinical relevance of the effects seen on pulmonary function and on exacerbation rate.
Slovenian: Obseg sprememb, opaženih pri več sekundarnih končnih točkah, pomaga pri oceni kliničnega pomena učinkov na delovanje pljuč in stopnjo poslabšanj.
English: To further address the concerns raised regarding the duration of the Applicant's clinical studies and to supplement the exacerbations data and other clinical data, the Applicant reviewed the FEV1 data and their predictive value.
Slovenian: Za nadaljnjo obravnavo pomislekov glede trajanja predlagateljevih kliničnih študij ter za dopolnitev podatkov o poslabšanjih in drugih kliničnih podatkov je predlagatelj pregledal podatke o FEV1 in njihovo napovedno vrednost.
English: Asthma control is one of two principal treatment goals in asthma management (the other being the reduction of exacerbation risk).
Slovenian: Obvladovanje in poslabšanja astme Obvladovanje astme je eden od dveh glavnih ciljev zdravljenja pri obravnavi astme (drugi je zmanjšanje tveganja za poslabšanje).
English: This provides further support for the clinical relevance of the effects seen with Iffeza.
Slovenian: To pomeni dodatno podporo kliničnemu pomenu učinkov, opaženih z zdravilom Iffeza.
English: Based on the results of the pharmacokinetic and clinical studies the objecting Member State stated that proof of equivalent bioavailability or control of inflammation is not established because:
Slovenian: Na podlagi rezultatov farmakokinetičnih in kliničnih študij je nasprotujoča država članica navedla, da ekvivalentna biološka razpoložljivost in obvladovanje vnetja nista dokazana, ker:
English: Nor does the literature offer any support for the notion that the exacerbations captured within the Applicant's clinical studies might not be adequate.
Slovenian: Literatura tudi nikakor ne podpira mnenja, da poslabšanja, ki so jih opazili v predlagateljevih kliničnih študijah, niso ustrezna.
English: Several endpoints which reflect these different facets of asthma control are modulated by long-acting β-agonists.
Slovenian: Več končnih točk, ki odražajo te različne vidike obvladovanja astme, uravnavajo β-agonisti z dolgotrajnim delovanjem.
English: • Therefore the Committee concluded that the benefit-risk balance of Iffeza in the applied indications is favourable.
Slovenian: Odbor je zato zaključil, da je razmerje med tveganji in koristmi uporabe zdravila Iffeza pri zadevnih indikacijah ugodno;
English: Supportive studies compared the efficacy and safety of Iffeza with other combination therapies.
Slovenian: S podpornimi študijami so primerjali učinkovitost in varnost zdravila Iffeza z drugimi kombiniranimi zdravljenji.
English: With regard to the duration of the pivotal studies (8-12 weeks), literature data support the view that treatment effects upon asthma control variables are maximal within 3 months and sustained thereafter.
Slovenian: V zvezi s trajanjem ključnih študij (8-12 tednov) podatki v literaturi podpirajo stališče, da so učinki zdravljenja na spremenljivke obvladovanja astme največji v roku treh mesecev in da se v nadaljevanju zdravljenja obdržijo.
English: These results do not imply that modest differences in pulmonary inhaled corticosteroid delivery will result in differences in exacerbation risk.
Slovenian: Ti rezultati ne pomenijo, da bodo skromne razlike v dostavi inhalacijskega kortikosteroida v pljuča spremenile tveganje za poslabšanje bolezni.
English: As such the applicant claimed that the asthma control results from the pivotal studies should logically be extrapolated to the longer-term.
Slovenian: Tako je predlagatelj zahteval, da se rezultati obvladovanja astme iz ključnih študij logično prenesejo na daljši rok.
English: In both claimed indications the previously used inhaled corticosteroid (ICS) is replaced by the inhaled corticosteroid in Iffeza for which such proof is required.
Slovenian: Pri obeh predlaganih indikacijah je predhodno uporabljeni inhalacijski kortikosteroid zamenjan z inhalacijskim kortikosteroidom v zdravilu Iffeza, za katerega se zahteva ta dokaz.
English: Published sources indicate that these treatment differences would at worst remain static and at best improve in favour of Iffeza over the longer-term.
Slovenian: Objavljeni viri navajajo, da se dolgoročno te razlike med zdravljenji v najslabšem primeru ne bi spremenile, v najboljšem pa izboljšale v korist zdravila Iffeza.
English: The CHMP supported the clinical study designs in the Phase III clinical development programme and the use of pre-dose FEV1 as the primary endpoint for efficacy in respect of corticosteroid effect.
Slovenian: Odbor CHMP je podprl zasnovo kliničnih študij v III. fazi kliničnega razvojnega programa in uporabo predodmernega FEV1 kot primarne končne točke za učinkovitost glede na učinek kortikosteroida.
English: The development programme also assessed the efficacy and safety of Iffeza administered either with or without a spacing device and investigated the efficacy and safety of Iffeza across relevant subgroups.
Slovenian: V razvojnem programu so ocenili tudi učinkovitost in varnost zdravila Iffeza, apliciranega z nastavkom ali brez njega, ter raziskali učinkovitost in varnost zdravila Iffeza v ustreznih podskupinah bolnikov.
English: Fluticasone propionate has been shown to reduce symptoms and exacerbations of asthma and to decrease airway reactivity to histamine and methacholine in patients with hyperreactive airways.
Slovenian: Dokazali so, da flutikazon propionat deluje proti simptomom in poslabšanjem astme ter da zmanjša odzivnost dihal na histamin in metaholin pri bolnikih s hiperreaktivnimi dihali.
English: In studies comparing a two-fold dose multiple of fluticasone propionate, dose response for exacerbations has never been shown.
Slovenian: V študijah, ki so primerjale dvojni odmerek flutikazon propionata, niso nikoli odkrili, da bi se poslabšanja odzivala na odmerek.
English: In its recent Consensus Statement on Asthma Control and Exacerbations the ATS/ERS identified pre-dose FEV1 as an essential endpoint in asthma studies and a predictor of future exacerbation risk.
Slovenian: V nedavnem uradnem stališču o obvladovanju astme in poslabšanj je skupina ATS/ERS opredelila predodmerni FEV1 kot bistveno končno točko v študijah astme in kot napovednik tveganja za poslabšanje v prihodnosti.
English: [“Step-up” indication]
Slovenian: „stopnjevanje zdravljenja“],
English: The exacerbations captured within the Applicant's studies are consistent with those described by the ATS/ERS (although differences in terminology do exist).
Slovenian: ki jih je opisala skupina ATS/ERS (čeprav obstajajo razlike v terminologiji).
English: Following oral inhalation of formoterol the onset of bronchodilatation is rapid, within 1 - 3 minutes, and bronchodilatation following a single dose lasts for 12 hours.
Slovenian: Bronhodilatacija nastopi hitro po peroralni inhalaciji formoterola, v 1-3 minutah, in po posameznem odmerku traja 12 ur.
English: This recommendation was made on the basis of several published studies which have demonstrated the predictive value of pre-dose and random/post-dose FEV1 over both the medium- and longer-term.
Slovenian: To priporočilo je temeljilo na več objavljenih študijah, ki so dokazale srednje- in dolgoročno napovedno vrednost predodmernega in naključnega/poodmernega FEV1.
English: The indication sought is the regular treatment of asthma where the use of a combination product (an inhaled corticosteroid and a long-acting β2 agonist) is appropriate:
Slovenian: Iskana indikacija je redno zdravljenje astme, kadar je uporaba kombinacije zdravil (inhalacijskega kortikosteroida in β2-agonista z dolgotrajnim delovanjem) ustrezna:
English: The leading global expert respiratory group (ATS/ERS) has recently proposed standardised definitions of clinically relevant exacerbations for use in future trials.
Slovenian: (ATS/ERS) je pred kratkim predlagala standardizirane opredelitve klinično pomembnih poslabšanj za uporabo v prihodnjih preskušanjih.
English: This endpoint (i.e. change in FEV1 from pre-dose at baseline) was designated a priori as the primary endpoint to assess corticosteroid effect.
Slovenian: Ta končna točka (tj. sprememba FEV1 glede na izhodiščno stanje pred odmerkom) je bila zasnovana a priori kot primarna končna točka za oceno učinka kortikosteroida.
English: In the frame of the referral under article 29(4), the Applicant was requested to respond to the following: “In the light of the available pharmacokinetic data showing a lower systemic exposure of the fluticasone propionate component of this fixed-dose combination product, there is concern that patients receiving this fixed-dose combination, whether for the 'substitution' indication or for the 'step-up' indication, may not experience the same level of efficacy in respect of long-term asthma control.
Slovenian: V okviru napotitve iz člena 29(4) je moral predlagatelj odgovoriti na naslednje: „Ob upoštevanju razpoložljivih farmakokinetičnih podatkov, ki kažejo manjšo sistemsko izpostavljenost komponenti flutikazon propionat v tem zdravilu s fiksno kombinacijo odmerkov, je skrb vzbujajoče, da učinkovitost pri bolnikih, ki dobivajo to kombinacijo fiksnih odmerkov, naj bo indikacija „nadomestno zdravljenje“ ali „stopnjevanje zdravljenja«, morda ni enaka, kar zadeva dolgoročno obvladovanje astme.
English: The inclusion of a second, lower dose of Iffeza (100µg/10µg) in the PD study was also instructive.
Slovenian: Poučna je bila tudi vključitev drugega, manjšega odmerka zdravila Iffeza (100 µg/10 µg) v farmakodinamično študijo.
English: The question posed by CHMP implied that the 67% relative bioavailability of the fluticasone propionate component of Iffeza compared with GSK fluticasone propionate pMDI may translate to a lesser inhaled corticosteroid effect and that this lesser effect would be best evaluated in a 6- to 12-month exacerbations study.
Slovenian: Odbor CHMP je z zastavljenim vprašanjem domneval, da 67-odstotna relativna biološka razpoložljivost flutikazon propionata v zdravilu Iffeza v primerjavi z vdihovalnikom s flutikazon propionatom GSK lahko pomeni manjši učinek inhalacijskega kortikosteroida in da bi bilo ta zmanjšani učinek najbolje oceniti v od 6- do 12-mesečni študiji poslabšanj.
English: The products are orally inhaled products and the combined therapy of an inhaled glucocorticosteroid and a selective long-acting ß2 adrenergic agonist is well established for use in the regular treatment of adults and children with asthma where the use of such a combination is deemed appropriate.
Slovenian: Kombinirana uporaba inhalacijskega glukokortikosteroida in selektivnega agonista ß2-adrenergičnih receptorjev z dolgotrajnim delovanjem je dobro uveljavljena za redno zdravljenje odraslih in otrok z astmo, kadar se uporaba take kombinacije zdi ustrezna.
English: Formoterol fumarate is a selective long-acting ß2 adrenergic agonist and exerts a preferential effect on ß2 adrenergic receptors on bronchial smooth muscle to produce relaxation and bronchodilatation.
Slovenian: Formoterol fumarat je selektiven agonist ß2-adrenergičnih receptorjev z dolgotrajnim delovanjem, ki s prednostnim učinkom na ß2-adrenergične receptorje na gladkem mišičju bronhijev doseže relaksacijo in bronhodilatacijo.
English: The pivotal clinical studies were designed to compare the efficacy and safety of Iffeza with its individual components administered separately and with its individual components administered together but inhaled from separate inhalers.
Slovenian: Ključne klinične študije so bile zasnovane za primerjavo učinkovitosti in varnosti zdravila Iffeza z ločeno aplikacijo posameznih komponent in s sočasno aplikacijo posameznih komponent, vendar vdihnjenih iz ločenih vdihovalnikov.
English: The PK data in Study FLT1501 were compared with a corresponding pharmacodynamic (PD) dataset from Study FLT3503.
Slovenian: Farmakokinetične podatke iz študije FLT1501 so primerjali z ustreznim naborom farmakodinamičnih podatkov iz študije FLT3503.
English: The CHMP noted that the differences of the magnitude observed between Iffeza and GSK fluticasone propionate in Study FLT1501 (67% relative bioavailability) are within the same range of variance as observed within patients (from inhalation to inhalation), between different batches of the same product and between different inhalers containing the same or more than one of the same active substances and are without adverse clinical consequences, and therefore are likely to be clinically irrelevant.
Slovenian: Odbor CHMP je ugotovil, da so razlike v obsegu, opažene med zdraviloma Iffeza in flutikazon propionat GSK v študiji FLT1501 (67-odstotna relativna biološka razpoložljivost), v enakem razponu variance, kot so ga opazili med bolniki (od inhalacije do inhalacije), med različnimi serijami istega zdravila in med različnimi vdihovalniki, ki vsebujejo isto ali več istih zdravilnih učinkovin in nimajo škodljivih kliničnih posledic, zato ni verjetno, da bi bile klinično pomembne.
English: The Applicant should discuss this concern in the light of the relatively short duration of the clinical study and the fact that the formoterol fumarate component in this fixed-dose combination might have masked a loss of control by controlling symptoms and bronchodilatation.”
Slovenian: Predlagatelj naj se posvetuje o tem zadržku glede na to, da je bila klinična študija razmeroma kratkotrajna, in glede na dejstvo, da je komponenta formoterol fumarat v tej kombinaciji fiksnih odmerkov prek obvladovanja simptomov in bronhodilatacije morda prikrila zmanjšano obvladovanje bolezni.“
English: These findings should be taken together with the results that show that the clinical effects of Iffeza are comparable with the clinical effects of GSK fluticasone propionate and Novartis formoterol fumarate given concomitantly.
Slovenian: Te ugotovitve je treba jemati skupaj z rezultati, ki kažejo, da so klinični učinki zdravila Iffeza primerljivi s kliničnimi učinki flutikazon propionata GSK in Novartis formoterol fumarata, kadar se uporabljata sočasno.
English: The Applicant stated that the choice of this endpoint is consistent with the Note for Guidance on Clinical Investigation of Medicinal Products for Treatment of Asthma - CPMP/EWP/2922/01); it is accepted as an appropriate endpoint to measure inhaled corticosteroid effect as per the CHMP OIP Guideline (CPMP/EWP/4151/00 Rev.1); and it is advocated as an essential endpoint in asthma studies by a joint expert committee of the American Thoracic Society and European Respiratory Society (ATS/ERS).
Slovenian: Predlagatelj je navedel, da je izbira te končne točke skladna z Navodili za klinične raziskave zdravil za zdravljenje astme - CPMP/EWP/2922/01, sprejeta je kot ustrezna končna točka za meritve učinka inhalacijskega kortikosteroida v skladu s smernico odbora CHMP za zdravila za peroralno inhalacijo (CPMP/EWP/4151/00 Rev.1) ter jo skupni strokovni odbor Ameriškega torakalnega društva in
English: Formoterol fumarate is particularly useful in patients with reversible airways obstruction who continue to experience symptoms despite treatment with an anti-inflammatory agent such as an inhaled corticosteroid.
Slovenian: Formoterol fumarat je še zlasti uporaben pri bolnikih z reverzibilno obstrukcijo dihalnih poti, pri katerih simptomi ne izginejo kljub zdravljenju s protivnetno učinkovino kot je inhalacijski kortikosteroid.
English: Assessment of the pre-dose FEV1 data in the three specified studies demonstrated that in two of the three studies formoterol fumarate has no effect upon pre-dose FEV1 whilst in the third study there was some residual formoterol effect upon pre-dose FEV1 but it was insufficient to explain the magnitude of the predose FEV1 treatment effect difference between Iffeza and fluticasone propionate pMDI.
Slovenian: Ocena podatkov o predodmernem FEV1 iz treh navedenih študij je pokazala, da v dveh od treh študij formoterol fumarat ni imel učinka na predodmerni FEV1, medtem ko je bilo v tretji študiji nekaj rezidualnega učinka formoterola na predodmerni FEV1, vendar je bil premajhen, da bi bilo z njim mogoče pojasniti obsežno razliko med učinkom zdravljenja na predodmerni FEV1 med zdravilom
English: Formoterol fumarate is used via the orally inhaled route in the management of patients with reversible airways obstruction.
Slovenian: Formoterol fumarat se uporablja s peroralno inhalacijo za zdravljenje bolnikov z reverzibilno obstrukcijo dihalnih poti.
English: • In the pharmacokinetic data presented systemic exposure of fluticasone was lower (67%) following Iffeza inhalation than following the concurrent inhalation of fluticasone and formoterol from monoproduct pMDIs.
Slovenian: • je bila v predloženih farmakokinetičnih podatkih sistemska izpostavljenost flutikazonu po inhalaciji zdravila Iffeza manjša (67 %) kot po sočasni inhalaciji flutikazona in formoterola iz vdihovalnikov z monozdravilom.
English: Fluticasone propionate is an inhaled glucocortosteroid with high local anti-inflammatory activity and a lower incidence of adverse effects than is seen with oral corticosteroids.
Slovenian: Flutikazon propionat je inhalacijski glukokortikosteroid z močnim lokalnim protivnetnim delovanjem in manjšo incidenco neželenih učinkov, kot jih opažajo pri peroralnih kortikosteroidih.
English: The CHMP was of the view that clinical data generated over 6 to 12 months to further elucidate the level of asthma control and to further assess exacerbation rates seen with Iffeza compared with fluticasone propionate administered concomitantly with formoterol fumarate or administered alone, are not required.
Slovenian: Odbor CHMP je menil, da klinični podatki, pridobljeni v od 6 do 12 mesecih, ki bi dodatno pojasnili raven obvladovanja astme in dodatno ocenili stopnje poslabšanj, opaženih z zdravilom Iffeza v primerjavi s flutikazon propionatom, uporabljenim v kombinaciji s formoterol fumaratom ali samostojno, niso potrebni.
English: It is intended for use in the management of asthma, formulated as a pressurised inhalation suspension in three strengths, and administered via a pressurised metered dose inhaler (pMDI).
Slovenian: Zdravilo je namenjeno za uporabo pri obravnavi astme, formulirano je kot inhalacijska raztopina pod tlakom v treh jakostih, uporablja pa se z odmernim vdihovalnikom na potisni plin (pMDI).
English: The CHMP was of the opinion that these findings suggest that the PK data from study FLT1501 do not reflect pulmonary deposition accurately and therefore in this study are not a valid surrogate for clinical efficacy of Iffeza.
Slovenian: Odbor CHMP je menil, da glede na ta odkritja farmakokinetični podatki iz študije FLT1501 ne odražajo pravilno odlaganja v pljučih, zato niso veljaven nadomestek za klinični učinek zdravila Iffeza.