FrancophonIA/ELRC3.0 huggingface dataset:
English: A total of 59 out of 85 patients (69.4%) from the placebo arm crossed over to open-label sunitinib following disease progression or unblinding at study closure.
Croatian: Sunitinib je u produljenju ispitivanja primalo ukupno 59 od 85 bolesnika (69,4%) iz placebo skupine.
English: l
Croatian: U
English: Pancreatitis has been observed uncommonly (< 1%) in patients receiving sunitinib for GIST or MRCC. No treatment-related pancreatitis was reported in the Phase 3 pNET study (see section 4.4).
Croatian: Nije prijavljen pankreatitis uzrokovan liječenjem u ispitivanju pNET-a faze III (vidjeti dio 4.4).
English: Post-marketing adverse reactions identified in clinical studies are also included.
Croatian: Obuhvaćene su i nuspojave zapažene u kliničkim ispitivanjima nakon stavljanja lijeka u promet.
English: No pulmonary embolism was reported for patients with pNET who received sunitinib in the Phase 3 study.
Croatian: U bolesnika s pNET-om koji su u ispitivanju faze III primali sunitinib nije zabilježena plućna embolija.
English: These could be signs and symptoms of bone damage in the jaw (osteonecrosis), see section 2.
Croatian: To mogu biti znakovi i simptomi oštećenja čeljusne kosti
English: Chest pain Pain
Croatian: PON UTO SRI ČET PET SUB NED
English: In the Phase 3 pNET study, 1 (1%) patient who received sunitinib had treatment-related fatal cardiac failure.
Croatian: U ispitivanju pNET-a faze III zatajenje srca sa smrtnim ishodom povezano s liječenjem zabilježeno je u 1 (1%) bolesnika koji je primao sunitinib.
English: Gelatin capsule with caramel cap and caramel body, printed with white ink “Pfizer” on the cap, “STN 50 mg” on the body, and containing yellow to orange granules.
Croatian: Na kapici je bijelom tintom otisnuta oznaka "Pfizer", a na tijelu "STN 50 mg".
English: - If you have or have had seizures.
Croatian: - ako imate ili ste ranije imali tegoba s bubrezima.
English: Skin exfoliation Skin reactionv
Croatian: pankreatitis analna fistula kolitis
English: Gelatin capsules with caramel cap and orange body, printed with white ink “Pfizer” on the cap, “STN 25 mg” on the body, and containing yellow to orange granules.
Croatian: Na kapici je bijelom tintom otisnuta oznaka "Pfizer", a na tijelu "STN 25 mg".
English: Vomiting Diarrhoea Dyspepsia Nausea Constipation
Croatian: Psihijatrijs ki poremećaji nesanica depresija
English: • Back pain, joint pain.
Croatian: • Bol u leđima, bol u zglobovima.
English: Ejection fraction decreased/abnormal.
Croatian: Smanjena/poremećena istisna frakcija
English: y Face oedema, oedema, and oedema peripheral.
Croatian: Edem lica, edem i periferni edem Povećana razina amilaza i amilaza
English: Transient ischaemic attack
Croatian: Srčani poremećaji ishemija miokarda k,*
English: Red iron oxide (E172) Titanium dioxide (E171) Yellow iron oxide (E172) Black iron oxide (E172)
Croatian: Ovojnica kapsule želatina željezov oksid, crveni (E172) titanijev dioksid (E171) željezov oksid, žuti (E172) željezov oksid, crni (E172)
English: Each capsule contains sunitinib malate equivalent to 12.5 mg sunitinib.
Croatian: Jedna kapsula sadrži 12,5 mg sunitiniba u obliku sunitinibmalata.
English: Titanium dioxide (E171) Yellow iron oxide (E172) Red iron oxide (E172) Black iron oxide (E172)
Croatian: Ovojnica kapsule želatina titanijev dioksid (E171) željezov oksid, žuti (E172) željezov oksid, crveni (E172) željezov oksid, crni (E172)
English: s
Croatian: v
English: - If you have or have had kidney problems.
Croatian: - ako imate ili ste ranije imali epileptičke napadaje.
English: Sutent 25 mg is supplied as hard gelatin capsules with caramel cap and orange body, printed with white ink “Pfizer” on the cap, “STN 25 mg” on the body, containing yellow to orange granules.
Croatian: Sutent 25 mg su tvrde želatinske kapsule s kapicom boje karamela i narančastim tijelom.
English: Gastrointestinal perforationq,* Pancreatitis Anal fistula Colitisr
Croatian: • gospinu travu (Hypericum perforatum) - biljni pripravci koji se koriste za liječenje depresije i tjeskobe.
English: Each capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib.
Croatian: Jedna kapsula sadrži 37,5 mg sunitiniba u obliku sunitinibmalata.
English: i
Croatian: NA
English: - Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide
Croatian: - Ovojnica kapsule: želatina, titanijev dioksid (E171), žuti željezov oksid (E172), crveni željezov oksid (E172) i crni željezov oksid (E172).
English: Each capsule contains sunitinib malate, equivalent to 50 mg of sunitinib.
Croatian: Jedna kapsula sadrži 50 mg sunitiniba u obliku sunitinibmalata.
English: 37.5 mg hard capsules Capsule content Mannitol (E421) Croscarmellose sodium Povidone (K-25) Magnesium stearate
Croatian: Tvrde kapsule od 37,5 mg Sadržaj kapsule manitol (E421) karmelozanatrij, umrežena povidon (K-25) magnezijev stearat
English: Each capsule contains sunitinib malate, equivalent to 25 mg of sunitinib.
Croatian: Jedna kapsula sadrži 25 mg sunitiniba u obliku sunitinibmalata.
English: 50 mg hard capsules Capsule content Mannitol (E421) Croscarmellose sodium Povidone (K-25) Magnesium stearate
Croatian: Tvrde kapsule od 50 mg Sadržaj kapsule manitol (E421) karmelozanatrij, umrežena povidon (K-25) magnezijev stearat
English: 25 mg hard capsules Capsule content Mannitol (E421) Croscarmellose sodium Povidone (K-25) Magnesium stearate
Croatian: Tvrde kapsule od 25 mg Sadržaj kapsule manitol (E421) karmelozanatrij, umrežena povidon (K-25) magnezijev stearat
English: Tumour haemorrhage*
Croatian: Mjera ishoda Sutent
English: • Liver failure.
Croatian: • Zatajenje jetre.
English: BLISTER OUTER CARTON - 37.5 MG CAPSULES
Croatian: KUTIJA S BLISTERIMA - 37,5 mg KAPSULE
English: 12.5 mg hard capsules Capsule content Mannitol (E421) Croscarmellose sodium Povidone (K-25) Magnesium stearate
Croatian: Tvrde kapsule od 12,5 mg Sadržaj kapsule manitol (E421) karmelozanatrij, umrežena povidon (K-25) magnezijev stearat
English: Rhabdomyolysis* Myopathy
Croatian: • ketokonazol, itrakonazol - lijekovi za liječenje gljivičnih infekcija
English: BLISTER OUTER CARTON - 12.5 MG CAPSULES
Croatian: KUTIJA S BLISTERIMA - 12,5 mg KAPSULE
English: Sutent 37.5 mg is supplied as hard gelatin capsules with yellow cap and yellow body, printed with black ink “Pfizer” on the cap, “STN 37.5 mg” on the body, containing yellow to orange granules.
Croatian: Sutent 37,5 mg su tvrde želatinske kapsule sa žutom kapicom i žutim tijelom.
English: Reporting of side effects
Croatian: Parametar djelotvornosti
English: Cases of myopathy and/or rhabdomyolysis, some with acute renal failure, have been reported.
Croatian: Poremećaji mišićno-koštanog sustava i vezivnog tkiva Prijavljeni su slučajevi miopatije i/ili rabdomiolize, ponekad uz akutno zatajenje bubrega.
English: Rare cases with fatal outcome have been observed in the postmarketing surveillance.
Croatian: Nakon stavljanja lijeka u promet zabilježeni su rijetki slučajevi sa smrtnim ishodom.
English: Blood creatine phosphokinase increased Blood thyroid stimulating hormone increased
Croatian: Krvožilni poremećaji hipertenzija duboka venska tromboza navale vrućine navale crvenila tumorsko krvarenje aneurizme i disekcije arterije
English: BLISTER OUTER CARTON - 25 MG CAPSULES
Croatian: KUTIJA S BLISTERIMA - 25 mg KAPSULE
English: Sutent 50 mg is supplied as hard gelatin capsules with caramel cap and caramel body, printed with white ink “Pfizer” on the cap, “STN 50 mg” on the body, containing yellow to orange granules.
Croatian: Sutent 50 mg su tvrde želatinske kapsule sa kapicom i tijelom boje karamela.
English: (not exceeding the total dose of 50 mg/day).
Croatian: 36 mg/m 2 te je povećana do doza koje su dosezale najvišu vrijednost od 40,4 mg/m 2 (bez prekoračenja ukupne doze od 50 mg/dan).
English: Sutent 12.5 mg is supplied as hard gelatin capsules with orange cap and orange body, printed with white ink “Pfizer” on the cap, “STN 12.5 mg” on the body, containing yellow to orange granules.
Croatian: Sutent 12,5 mg su tvrde želatinske kapsule s narančastom kapicom i narančastim tijelom.
English: Cases of ONJ have been reported in patients treated with Sutent.
Croatian: U bolesnika liječenih lijekom Sutent zabilježeni su slučajevi osteonekroze čeljusti.
English: Haematological disorders (e.g., neutropenia, thrombocytopenia, and anaemia) are amongst the most common adverse drug reactions.
Croatian: Među najčešćim nuspojavama na lijek su hematološki poremećaji (npr. neutropenija, trombocitopenija i anemija).
English: The CHMP considers that:
Croatian: CHMP je mišljenja da:
English: Annex
Croatian: Prilog
English: This is in agreement with the conclusions of the Scientific Advisory Group (SAG) consulted.
Croatian: To je u skladu sa zaključcima konzultirane znanstvene savjetodavne grupe (SAG-a).
English: • Efficacy issues
Croatian: • Problemi djelotvornosti
English: Scientific conclusions and grounds for refusal of the variation presented by the European Medicines Agency
Croatian: Znanstveni zaključci i razlozi za odbijanje izmjena dostavljenih koje iznosi Europska agencija za lijekove
English: According to this analysis, 84% of the PFS events could be considered unequivocal.
Croatian: U skladu s ovom analizom, 84% PFS događaja nije se moglo smatrati nedvosmislenim.
English: However, in this analysis, progressive disease (which suffers of the limitations described above) was included as a deterioration event.
Croatian: No u ovoj analizi progresivna bolest (koja je obilježena prethodno navedenim ograničenjima) uključena je kao događaj deterioracije.
English: Overall, the toxicity of bevacizumab in this regimen and combination did not, in itself, raise major concerns.
Croatian: Načelno gledano, toksičnost bevacizumaba u ovom režimu i kombinaciji sami po sebi nisu bili razlog za veću zabrinutost.
English: Similar limitations apply to the determination of performance status.
Croatian: Slična ograničenja primjenjiva su na utvrđivanje statusa učinkovitosti.
English: However, there are no established methods of analysis that can remedy this after cross-over has occurred.
Croatian: No, nema utvrđenih metoda za analizu koje to mogu ispraviti nakon što je nastupio prijelaz.
English: In addition, some assessments may have been influenced by knowledge of progression status.
Croatian: Nadalje, određene ocjene mogu biti pod utjecanjem saznanja o statusu progresije.
English: Recommendations following re-examination
Croatian: Preporuke nakon ponovnog pregleda
English: Disease progression was assessed using adapted Macdonald criteria (Chinot et al., 2013).
Croatian: Progresija bolesti ocjenjena je primjenom prilagođenog Macdonaldovog kriterija (Chinot et al., 2013).
English: The CHMP assessed all the detailed grounds for re-examination and argumentations presented by the applicant.
Croatian: CHMP je ocijenio sve detaljne razloge za ponovni pregled i argumentaciju koju su dostavili podnositelji zahtjeva.
English: This analysis resulted in an estimated benefit of smaller magnitude, based on an analysis that, necessarily but problematically, introduces some informative censoring.
Croatian: Ova analiza rezultirala je procjenom koristi manjeg raspona na temelju analize kojom se, neophodno no problematično, uvodi određeno informativno cenzuriranje.
English: However, in the absence of established efficacy, the toxicity of this regiment cannot be considered acceptable.
Croatian: No, u slučaju izostanka utvrđene djelotvornosti, toksičnost ovog režima ne može se smatrati prihvatljivim.
English: These apparent responses are not always necessarily indicative of a true antiglioma effect.
Croatian: Ovi očiti odgovori nisu uvijek neophodno indikativni za valjano protugliomno djelovanje.
English: These analyses should be interpreted with caution since relevant data were not collected systematically after disease progression and the consequent impact of (potentially informative) censoring on the results is unclear.
Croatian: Ove se analize trebaju tumačiti s određenom dozom opreza budući da relevantni podaci nisu prikupljeni sistematski nakon progresije bolesti, a posljedično djelovanje (potencijalno informativno) cenzuriranja na rezultate nije jasno.
English: • In the absence of established efficacy, a positive benefit-risk balance has not been established.
Croatian: • u odsutnosti utvrđene djelotvornosti, nije utvrđen pozitivan omjer koristi i rizika.
English: Overall survival (OS) and progression-free survival (PFS) as assessed by the investigator were co-primary endpoints of the trial.
Croatian: Stope ukupnog preživljenja (OS) i preživljenja bez progresije (PFS), kako su ocijenili ispitivači, bile su zajedničke primarne točke ispitivanja.
English: Overall conclusion on grounds for re-examination
Croatian: Cjelokupan zaključak o razlozima za ponovni pregled
English: Nominally, statistically significant results were retained for some parameters when PD was not counted as a deterioration event.
Croatian: Nominalno, statistički značajni rezultati su rezervirani za određene parametre u slučaju kada PD nije uzet u obzir kao događaj propadanja.
English: Bevacizumab was administered at a dose of 10 mg/kg every two weeks in the concurrent phase and the maintenance phase, and at a dose of 15 mg/kg every three weeks in the monotherapy phase.
Croatian: Bevacizumab je primjenjivan u dozi od 10 mg/kg svaka dva tjedna u kontaminantnoj fazi i fazi održavanja, te u dozi od 15 mg/kg svaka tri tjedna u fazi monoterapije.
English: An effect was claimed based on analysis of the secondary endpoint time to definitive deterioration in HRQoL.
Croatian: Pretpostavljeno je djelovanje na temelju analize vremena sekundarne završne točke do konačne deterioracije u HRQoL-u.
English: Other endpoints including corticosteroid use, and sign and symptoms of GMB also need special consideration in light of the nature of the mechanism of bevacizumab.
Croatian: Druge završne točke, uključujući uporabu kortikosteroida, kao i znakove i simptome GMB-a također zahtijevaju razmatranje u svjetlu prirode mehanizma djelovanja bevacizumaba.
English: Regarding clinical outcomes, the applicant proposed that only maintenance of QoL to the time of disease progression may be expected, and this can be accepted.
Croatian: Vezano uz kliničke ishode, podnositelj zahtjeva predložio je da se može očekivati samo održavanje QoL do vremena progresije bolesti, a to se može prihvatiti.
English: The analyses of the secondary endpoint health-related quality of life (HRQoL) did not show an advantage of addition of bevacizumab to standard treatment.
Croatian: Analizama sekundarne završne točke kvalitete života povezane sa zdravljem (HRQoL) nije dokazala prednost dodavanja bevacizumaba standardnoj terapiji.
English: Furthermore, it was unclear to what extent HRQoL data collection could have been influenced by knowledge of the response status.
Croatian: Nadalje, nejasno je u kojoj se mjeri moglo utjecati na zbir podataka za HRQoL saznanjem o statusu odgovora.
English: Summary of the applicant's response to the grounds for re-examination:
Croatian: Sažetak odgovora podnositelja zahtjeva na razloge za ponovni pregled:
English: Changes in corticosteroid use, normally considered indicative for disease progression are confounded by the overlapping physiological effects of corticosteroids and bevacizumab.
Croatian: Promjene u primjeni kortikosteroida, koje se normalno smatraju indikativnima za progresiju bolesti, pogrešno su zamijenjene preklapajućim fiziološkim djelovanjem kortikosteroida i bevacizumaba.
English: Due to these reasons, the clinical relevance of the observed difference in the primary analysis of PFS is unknown.
Croatian: Slijedom navedenog, klinička relevantnost uočenih razlika u primarnoj analizi PFS-a nije poznata.
English: Although standard response assessment criteria have been further developed (RANO criteria) aiming to minimise this issue and inform treatment decisions, validation of these criteria as clinical benefit endpoints is still ongoing (Wen et al., 2010).
Croatian: Iako su standardni kriteriji za ocjenu odgovora dalje razvijeni (kriteriji RANO) sa ciljem smanjivanja ovog problema i donošenja informiranih odluka o liječenju, još je uvijek u tijeku potvrda ovih kriterija kao završnih točaka za kliničku korist (Wen et al., 2010).
English: Finally, the applicant provided a post-hoc analysis in line with the RANO criteria (Wen et al., 2010), which are the current standard used in clinical trials.
Croatian: Naposljetku, podnositelj zahtjeva dostavio je post-hoc analizu u skladu s RANO kriterijima (Wen et al., 2010.), koji predstavljaju aktualni standard primijenjen u kliničkim ispitivanjima.
English: Radiotherapy and TMZ were administered in line with standard regimens used in the setting of newly diagnosed glioblastoma (Stupp et al., 2005).
Croatian: Radioterapija i TMZ primijenjeni su u skladu sa standardnim režimima korištenima u okruženju novodijagnosticiranog glioblastoma (Stupp et al., 2005).
English: While the Applicant acknowledged that limited data was captured beyond the time of progression, they contended that this does not diminish the value of the data captured on study.
Croatian: Iako je podnositelj zahtjeva priznao da su podaci prikupljeni nakon vremena progresije, argumentirali su da to ne umanjuje vrijednost podataka prikupljenih ispitivanjem.
English: The applicant concluded that despite the obvious flaws and biases of the exploratory survival analyses these analyses indicated a beneficial effect of bevacizumab.
Croatian: Podnositelj zahtjeva zaključio je da usprkos očitim nedostacima i pristranosti eksploratornih analiza preživljenja, ove analize ukazuju na korisno djelovanje bevacizumaba.
English: The primary analysis of PFS showed a statistically significant difference in favour of bevacizumab (HR 0.64, 95%CI 0.55-0.74; p<0.0001).
Croatian: Primarnom analizom PFS-a dokazana je statistički značajna razlika u korist bevacizumaba (HR 0,64, 95% CI 0,55-0,74; p<,.0001).
English: Based on the arguments of the applicant and all the supporting data on safety and efficacy, the CHMP re-examined its initial opinion and in its final opinion concluded by majority decision that the efficacy of the above mentioned medicinal product is not sufficiently demonstrated, and, therefore maintains its recommendation for the refusal of the variation of the Marketing Authorisation for the above mentioned medicinal product.
Croatian: Na temelju argumenata koje je dostavio podnositelj zahtjeva, i svih podataka u prilog sigurnosti i djelotvornosti, CHMP je ponovno preispitao svoje prvotno mišljenje i u svojem konačnom mišljenju zaključio je većinskom odlukom da djelotvornost prethodno navedenog lijeka nije dokazana u dostatnoj mjeri, te da stoga ostaje pri svojoj preporuci za odbijanje preporuka za izmjenu odobrenja za stavljanje lijeka u promet za prethodno navedeni lijek.
English: In particular, the applicant did not clearly justify how the criteria chosen to exclude specific patients or events in the various sensitivity analyses were able to address the biases/uncertainties around the assessment of progression.
Croatian: Podnositelj zahtjeva posebice nije jasno opravdao kako su kriteriji odabrani za isključivanje specifičnih bolesnika ili događaja u različitim analizama osjetljivosti mogli odgovoriti na pristranosti/nesigurnosti vezane uz ocjenu progresije.
English: It has not been established that the most likely cause for the failure to demonstrate an OS benefit is confounded by post-progression treatments (including crossover to bevacizumab) rather than lack of an effect.
Croatian: Nije utvrđeno da je najizgledniji izgled propusta dokazivanja koristi OS-a pogrešno zamijenjen post progresijom liječenja (uključujući prijelaz na bevacizumab), umjesto izostanak djelovanja.
English: All the additional analyses cannot exclude the possibility of important bias and the estimated effect is not regarded as sufficiently reliable to conclude that a clinically relevant therapeutic efficacy has been established.
Croatian: Sve dodatne analize ne mogu isključiti mogućnost važne pristranosti, a procijenjeno djelovanje ne smatra dostatno pouzdanim kako bi se zaključilo da je utvrđena klinički relevantna terapijska djelotvornost.
English: Regarding the MRI evaluation of disease progression, the CHMP maintained the view that the impact of the use of adapted criteria in Study BO21990 remains unclear.
Croatian: Vezano uz ocjenu progresije bolesti na temelju MRI-a, CHMP je zadržao svoje mišljenje da utjecaj primjene na prilagođene kriterije ispitivanja BO21990 ostaje nejasan.
English: Reliability of PFS: The applicant considered that the robustness and reliability of the primary analysis of PFS was confirmed in a number of predefined and post-hoc sensitivity analyses.
Croatian: Pouzdanost PFS-a: podnositelj zahtjeva smatrao je da je robusnost i pouzdanost primarne analize PFS-a potvrđena brojem analiza prethodno definirane i post-hoc osjetljivosti.
English: At the time of disease progression, the data indicated a trend for deterioration in functional status and HRQoL compared to the assessments prior to progression, which underscores the clinical importance for the patients of delaying the time until disease progression.
Croatian: U trenutku progresije bolesti, podaci su ukazivali na trend deterioracije u funkcionalnom statusu i HRQoL-u u usporedbi s ocjenama prije progresije, čime se i naglašava klinički značaj za bolesnika odgode nastupanja progresija bolesti.
English: The applicant provided an additional post-hoc PFS analysis where all progressions exclusively based on non-index lesions were not regarded as a PFS event.
Croatian: Podnositelj zahtjeva dostavio je dodatnu analizu post-hoc PFS-a, u kojoj su se sve progresije ekskluzivno temeljile na neindeksiranim lezijama i nisu smatrane PFS događajem.
English: The most frequent toxicity associated with the bevacizumab treatment group were gastrointestinal (nausea, constipation, vomiting), alopecia, fatigue, thrombocytopenia, headache and hypertension.
Croatian: Najčešće toksičnosti povezane s grupama koje su primile liječenje bevacizumabom su gastrointestinalna toksičnost (mučnina, zatvor, povraćanje), alopecija, umor, trombocitopenija, glavobolja i hipertenzija.
English: Following the above CHMP opinion, the applicant requested re-examination and submitted on 22 July 2014 its detailed grounds for the request for re-examination of the CHMP opinion recommending the refusal of the granting of the marketing authorisation.
Croatian: Nakon donošenja prethodnog mišljenja CHMP-a, podnositelj zahtjeva zatraženo je ponovni pregled i dostavio je dana 22. srpnja 2014. svoje detaljne razloge za zahtjev za ponovni pregled mišljenja CHMP-a kojim se preporuča odbijanje izdavanja odobrenja za stavljanje lijeka u promet.
English: The number of PD events may have been overestimated in the placebo arm and underestimated in the bevacizumab arm.
Croatian: Broj događaja PD-a je vjerojatno precijenjen u grupi koja je uzimala placebo i podcijenjen u grupi koja je uzimala bevacizumab.
English: The median PFS was estimated to be 10.6 months in the bevacizumab arm and 6.2 months in the placebo arm.
Croatian: Srednja vrijednost PFS-a procijenjena je na 10,6 u grupi koja je uzimala bevacizumab i 6,2 mjeseca u grupi koja je uzimala placebo.
English: • The efficacy of bevacizumab in combination with radiotherapy and temozolomide for the treatment of adult patients with newly diagnosed glioblastoma has not been sufficiently demonstrated;
Croatian: • djelotvornost bevacizumaba u kombinaciji s radioterapijom i temozolomidom za liječenje odraslih bolesnika s novodijagnosticiranim glioblastomom nije dokazana u dostatnoj mjeri;
English: However, the CHMP concluded that the positive effects claimed by the applicant are mainly driven by the inclusion of PD as an event in these analyses, and therefore, they cannot provide independent support or insight into the clinical benefits of delaying progression.
Croatian: No, CHMP je zaključio da je pozitivno djelovanje za koje podnositelj zahtjeva tvrdi da postoji uglavnom poticano uvrštavanjem PD-a kao događaja u ove analize, te stoga ne mogu pružiti neovisnu podršku ni uvid u kliničke koristi odgađanja progresije.