FrancophonIA/ELRC3.0 huggingface dataset:
English: There was no restriction on the degree of short stature and the children had to be pre-pubertal at start of treatment.
Slovenian: Glede stopnje nizke rasti ni bilo omejitve, otroci pa so morali biti ob začetku zdravljenja v predpubertetnem obdobju.
English: Hence, 35 of 41 (85%) children with PWS had a height within the reference range for normal children after Norditropin treatment.
Slovenian: Iz tega sledi, da je 35 od 41 (85 %) otrok s PWS imelo višino znotraj referenčnega območja za normalne otroke po zdravljenju z zdravilom Norditropin.
English: Only 33 children were included in the primary efficacy analysis and selection bias cannot be excluded due to the design of the study.
Slovenian: V analizo primarne učinkovitosti je bilo vključenih le 33 otrok, zaradi zasnove študije pa ni mogoče izključiti pristranskosti izbire.
English: The number of children with an HSDS above -2 was 19 (46%) children at baseline, 27 (66%) children after 1 year of treatment and 35 (85%) children at last observation.
Slovenian: Število otrok s HSDS nad -2 je bilo 19 (46 %) otrok ob začetku, 27 (66 %) otrok po 1 letu zdravljenja in 35 (85 %) otrok ob zadnjem opazovanju.
English: The mean age at inclusion was 3.8 years (min 0.4 years; max 12.2 years).
Slovenian: Povprečna starost ob vključitvi je bila 3,8 leta (najnižja 0,4 leta; najvišja 12,2 leta).
English: The CHMP was requested to give its opinion on whether the marketing authorisations should be varied to include the indication:
Slovenian: Odbor za zdravila za uporabo v humani medicini (CHMP) je zaprosila za mnenje o tem, ali naj bodo dovoljenja za promet z zdravili spremenjena tako, da bodo vključevala indikacijo:
English: Data on final adult heights are not available.
Slovenian: Podatki o končni višini odraslih oseb niso na voljo.
English: The CHMP concluded that given the retrospective design of the study, selection bias cannot be excluded.
Slovenian: Odbor CHMP je sklenil, da glede na retrospektivno zasnovo študije ni mogoče izključiti pristranskosti izbire.
English: The majority of events were of mild/moderate severity.
Slovenian: Neželeni učinki so bili večinoma blagi/zmerni.
English: Data on change in height velocity were not considered valid, as data on pre-trial height measurements were incomplete.
Slovenian: Podatki o spremembi v hitrosti rasti niso bili upoštevani kot veljavni, saj podatki o meritvah višine pred preskušanjem niso bili popolni.
English: Norditropin contains somatropin which is a human growth hormone produced by recombinant DNA technology that has received marketing authorisation in the European Union through the Mutual Recognition Procedure (MRP).
Slovenian: Zdravilo Norditropin vsebuje somatropin, ki je humani rastni hormon, pridobljen s tehnologijo rekombinantne DNK, za katerega je bilo pridobljeno dovoljenje za promet z zdravilom v Evropski uniji v postopku z medsebojnim priznavanjem.
English: Body composition was improved, with an estimated mean increase in body mass of 9.9% and a corresponding reduction in fat mass of 9.9% after 1 year of Norditropin treatment.
Slovenian: Sestava telesa se je izboljšala z ocenjenim povprečnim povečanjem telesne mase za 9,9 % in z ustrezajočim zmanjšanjem maščobne mase za 9,9 % po prvem letu zdravljenja z zdravilom Norditropin.
English: Sleep apnoea and sudden death have been reported in clinical practice after initiating therapy in patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnoea, or unidentified respiratory infection.
Slovenian: V klinični praksi so poročali o apneji v spanju in nenadni smrti po začetku zdravljenja pri bolnikih s Prader-Willijevim sindromom, pri katerih je bil prisoten en ali več od naslednjih dejavnikov tveganja: huda debelost, anamneza obstrukcije zgornjih dihalnih poti ali apneja v spanju ali neugotovljena okužba dihal.
English: Height at baseline was only available for 37 patients.
Slovenian: Višina ob izhodišču je bila na voljo le za 37 bolnikov.
English: In Europe, two recombinant GH products are approved for the treatment of children with PWS.
Slovenian: V Evropi sta za zdravljenje otrok s PWS odobrena dva rekombinantna rastna hormona.
English: The recommended dose is not the same as the one studied in the GHLiquid-1961 which was chosen at the discretion of the physician and was on average 0.03 mg/kg/day.
Slovenian: Priporočeni odmerek ni enak odmerku, ki je bil preučen v študiji GHLiquid-1961 in izbran po presoji zdravnika, in je bil v povprečju 0,03 mg/kg/dan.
English: Apart from the aforementioned general deficiency some other aspects of the GHLiquid-1961 study raised concerns to the CHMP namely the validity and the quality of the study results and are summarised below.
Slovenian: Poleg prej omenjene splošne pomanjkljivosti je odbor CHMP izrazil zadržke tudi v zvezi z nekaterimi drugimi vidiki študije GHLiquid-1961, zlasti v zvezi z veljavnostjo in kakovostjo rezultatov študije, ki so povzeti spodaj.
English: The data from the study that were submitted with the application of Novo Nordisk to support the proposed indication were not considered sufficient (open-label, non-controlled and retrospective study) and of good quality (wide range of doses used, height measurements incomplete) by the objecting Member States.
Slovenian: Podatke iz študije, ki jih je družba Novo Nordisk predložila vlogi v podporo predlagani indikaciji, so ugovarjajoče države članice zavrnile kot nezadostne (odprta, nekontrolirana in retrospektivna študija) in nekakovostne (širok razpon uporabljenih odmerkov, nepopolno merjenje telesne višine).
English: The inclusion criteria were pre-pubertal children with genetically diagnosed PWS, treated with Norditropin for at least 1 year in the centre.
Slovenian: Vključitveni kriteriji so zajemali predpubertetne otroke z genetsko diagnosticiranim PWS, ki so jih z zdravilom Norditropin vsaj eno leto zdravili v centru.
English: A total of 128 adverse events were reported in 31 (75.6%) children with PWS during Norditropin exposure (mean exposure 4.1 years, range 0.3 to 9.5 years).
Slovenian: Skupno so poročali o 128 neželenih dogodkih pri 31 (75,6 %) otrocih s PWS v času izpostavljenosti zdravilu Norditropin (povprečna izpostavljenost je znašala 4,1 leta, z razponom od 0,3 do 9,5 leta).
English: The most frequent probably/possibly related adverse events were scoliosis (in 8 children, 19.5%) and sleep apnoea (in 3 children, 7.3%).
Slovenian: Najbolj pogosti verjetno/mogoče povezani neželeni dogodki so bili skolioza (pri 8 otrocih, 19,5 %) in apneja v spanju (pri 3 otrocih, 7,3 %).
English: No additional information was given by the MAH on the other PWS children for which informed consent was not obtained.
Slovenian: Imetnik dovoljenja za promet z zdravilom ni podal nobenih dodatnih informacij o drugih otrocih s PWS, za katere ni pridobil prostovoljnega soglasja.
English: In addition, accepting the same recommended dose as for other GH products was not considered appropriate as Norditropin has not shown comparable efficacy and those two products have different dose recommendations for other indications, i.e. Turner syndrome and chronic renal disease.
Slovenian: Potrditev enakega priporočenega odmerka kot za drugi dve zdravili z rastnim hormonom se je prav tako štela za neustrezno, saj zdravilo Norditropin ni prikazalo primerljive učinkovitosti, povrhu tega pa drugi dve zdravili za druge indikacije, npr. za Turnerjev sindrom in kronično ledvično bolezen, priporočata različne odmerke.
English: The most frequent adverse events were respiratory tract infections which are common in young children (14.6% of children) and scoliosis which is common in PWS (19.5% of children).
Slovenian: Najpogostejši neželeni učinki so bile okužbe dihalnih poti, ki so pogoste pri mlajših otrocih (14,6 % otrok) in skolioza, ki je pogosta pri PWS (19,5 % otrok).
English: Regarding efficacy on the basis of the available data the CHMP concluded that the demonstration of efficacy for Norditropin in PWS is based on limited and unreliable data of apparent poor quality.
Slovenian: Na podlagi razpoložljivih podatkov je odbor CHMP v zvezi z učinkovitostjo sklenil, da temelji prikaz učinkovitosti za zdravilo Norditropin pri zdravljenju PWS na omejenih in nezanesljivih podatkih očitne slabe kakovosti.
English: Short stature, mental retardation, behavioural problems, hormonal dysfunctions, poor muscle tone and hyperphagia as well as hypoactivity are among its features.
Slovenian: Nekatere značilnosti PWS so nizka rast, duševna zaostalost, vedenjske motnje, hormonske motnje, slab mišični tonus, hiperfagija in hipoaktivnost.
English: The quality of the data was also considered questionable given the fact that basic information such as baseline height was missing in 10% of patients.
Slovenian: Za vprašljivo so ocenili tudi kakovost podatkov, saj so osnovne informacije, denimo izhodiščna višina, manjkale za kar 10 % bolnikov.
English: • The Committee reviewed all available data submitted by the marketing authorisation holder, to support the safety and efficacy of Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names in the applied indication “Improvement of growth and body composition in children with Prader-Willi syndrome (PWS) confirmed by appropriate genetic testing”.
Slovenian: • Odbor je pregledal vse razpoložljive podatke, ki jih je predložil imetnik dovoljenja za promet z zdravilom v podporo varnosti in učinkovitosti zdravil Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezanih imen za vloženo indikacijo „Izboljšanje rasti in sestave telesa pri otrocih s Prader-Willijevim sindromom (PWS), potrjenim z ustreznim genetskim testiranjem“;
English: The secondary objectives were to evaluate in the same population the change in HSDS from start of treatment to last observation during Norditropin treatment (referenced to a PWS population), change in body composition (lean body mass and fat mass), height velocity (HV) and change in HV.
Slovenian: Sekundarni cilji so bili oceniti spremembe HSDS od začetka zdravljenja do zadnjega opazovanja v okviru zdravljenja z zdravilom Norditropin v isti populaciji (glede na populacijo s PWS), spremembe v sestavi telesa (mršava telesna masa in maščobna masa), hitrost rasti in spremembe v hitrosti rasti.
English: No data on final adult height were provided.
Slovenian: Podatki o končni višini odraslih oseb niso bili predloženi.
English: IGF-1 SDS at baseline was only available for 28 patients.
Slovenian: Vrednost standardnega odstopanja (SDS) za IGF-1 ob izhodišču je bila na voljo le za 28 bolnikov.
English: Taking into consideration the above mentioned data, the CHMP concluded that the provided study GHLiquid-1961 forming the basis for the application to extend the indication for Norditropin in children with PWS was uncontrolled, open-label and retrospective and not in accordance with the methodological standards for pivotal evidence.
Slovenian: Ob upoštevanju zgoraj navedenih podatkov je odbor CHMP zaključil, da je predložena študija GHLiquid-1961, ki predstavlja temelj vloge za razširitev indikacije za zdravilo Norditropin pri otrocih s PWS, nekontrolirana, odprta in retrospektivna študija, ki ni v skladu z metodološkimi standardi za ključni dokaz.
English: Furthermore, a wide range of doses has been used in the retrospective study (mean dose 0.03 mg/kg/day - up to 0.06 mg/kg/day).
Slovenian: V retrospektivni študiji je bil uporabljen širok razpon odmerkov (povprečni odmerek je bil 0,03 mg/kg/dan vse do 0,06 mg/kg/dan).
English: In conclusion, the data provided by the MAH in particular to support efficacy are insufficient to sustain the extension of indication in PWS.
Slovenian: Podatki, ki jih je v podporo učinkovitosti predložil imetnik dovoljenja za promet z zdravilom, torej ne zadoščajo za razširitev indikacije pri PWS.
English: • The Committee is also of the opinion that the particulars submitted in support of the application to extend the indications of Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names do not comply with the requirements of a product authorised on the basis of Article 8(3) of Directive 2001/83/EC.
Slovenian: • Odbor tudi meni, da podrobni podatki, ki so bili predloženi v podporo vlogi za razširitev indikacij za zdravila Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezana imena, niso v skladu z zahtevami zdravila, ki je bilo odobreno na podlagi člena 8(3) Direktive 2001/83/ES;
English: However, considering requests from some Concerned Member States (CMS) during the CMDh referral, the MAH agreed that the dose recommendation for PWS could be 0.035 mg/kg/day, the same as for the other two GH products approved in the same indication.
Slovenian: Vendar pa se je ob upoštevanju zahtev nekaterih zadevnih držav članic v okviru napotitvenega postopka Usklajevalne skupine za postopek z medsebojnim priznavanjem in decentralizirani postopek za zdravila za uporabo v humani medicini (CMDh) imetnik dovoljenja za promet z zdravilom strinjal, da bi lahko bil priporočeni odmerek za PWS 0,035 mg/kg/dan, torej enak kot za drugi dve zdravili z rastnim hormonom, ki sta odobreni za enako indikacijo.
English: On 14 May 2010, the MAH submitted a type II variation via the MRP for Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names (DK/H/0001/005-007 and 011016/II/078), to request an extension of the indications.
Slovenian: Dne 14. maja 2010 je imetnik dovoljenja za promet z zdravilom predložil spremembo tipa II v postopku z medsebojnim priznavanjem za zdravila Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezana imena (DK/H/0001/005-007 in 011-016/II/078), s katero je zaprosil za razširitev indikacij.
English: In the variation application dossier, the recommended dose from Novo Nordisk for the treatment of short stature and altered body composition in children with PWS was 0.025 to 0.035 mg/kg/day.
Slovenian: V vlogi za spremembo dovoljenja za promet z zdravilom je bil priporočeni odmerek družbe Novo Nordisk za zdravljenje nizke rasti in spremenjene sestave telesa pri otrocih s PWS 0,025 do 0,035 mg/kg/dan.
English: The primary objective of the study was to investigate changes in height standard deviation score (HSDS) in response to 1 year of Norditropin treatment in children with PWS (referenced to a PWS population).
Slovenian: Primarni cilj študije je bil raziskati spremembe v vrednosti standardnega odklona telesne višine (HSDS) kot odgovor na enoletno zdravljenje z zdravilom Norditropin pri otrocih s PWS (glede na populacijo s PWS).
English: This was a retrospective, observational, open-label, multicentre, multinational study in children with PWS treated with Norditropin off-label for short stature.
Slovenian: To je bila retrospektivna, opazovalna, odprta, multicentrična, večnacionalna študija pri otrocih s PWS, ki so bili zdravljeni z zdravilom Norditropin zaradi nizke rasti, kar ni navedeno v indikacijah.
English: Benefit-Risk
Slovenian: Ocena razmerja med koristmi in tveganji
English: The actual fat mass percentage was 38.2% at baseline, 28.1% at Year 1 and 27.1% at last observation.
Slovenian: Dejanski odstotek maščobne mase je znašal 38,2 % na začetku, 28,1 % ob prvem letu in 27,1 % ob zadnjem opazovanju.
English: The actual lean body mass percentage was 61.8% at baseline, 71.9% at Year 1 and 72.9% at last observation.
Slovenian: Dejanski odstotek mršave telesne mase je znašal 61,8 % na začetku, 71,9 % ob prvem letu in 72,9 % ob zadnjem opazovanju.
English: The estimated gain in HSDS was 1.3 to last observation (approximately 6 years).
Slovenian: Ocenjeno povečanje HSDS je znašalo 1,3 do zadnjega opazovanja (približno 6 let).
English: The CHMP concluded that the rationale for the proposed dose (i.e. 0.035 mg/kg/day) is still unclear.
Slovenian: Odbor CHMP je sklenil, da je utemeljitev za predlagani odmerek (tj. 0,035 mg/kg/dan) še vedno nejasna.
English: The CHMP concluded that the rationale for the proposed dose (i.e. 0.035 mg/kg/day) is unclear.
Slovenian: Odbor CHMP je sklenil, da je utemeljitev za predlagani odmerek (tj. 0,035 mg/kg/dan) nejasna.
English: HSDS improved from a baseline mean of -1.8 to -1.2 after 1 year and to0.7 at last observation (approximately 6 years).
Slovenian: HSDS se je izboljšala z izhodiščne srednje vrednosti -1,8 na -1,2 po 1 letu in na -0,7 ob zadnjem opazovanju (približno 6 let).
English: Moreover, the quality of the data is questionable, as height measurements at baseline were missing in 10% of the subjects.
Slovenian: Vprašljiva je tudi kakovost podatkov, saj so meritve izhodiščne višine manjkale za 10 % oseb.
English: The mean HSDS for this subgroup was -0.6 at Year 1 and -0.4 at last observation.
Slovenian: Povprečna HSDS za to podskupino je bila -0,6 ob enem letu in -0,4 ob zadnjem opazovanju.
English: No new safety concern emerged from the submitted retrospective data.
Slovenian: Iz predloženih retrospektivnih podatkov niso izhajali nobeni novi zadržki glede varnosti zdravila.
English: Overall summary of the scientific evaluation of Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names (see annex I)
Slovenian: Splošni povzetek znanstvenega vrednotenja zdravil Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezanih imen (glejte Prilogo I)
English: It is also considered that the data are unreliable and therefore the benefit risk balance of Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names in the applied indication is unfavourable.
Slovenian: Podatki se štejejo tudi za nezanesljive, zato je razmerje med koristmi in tveganji pri uporabi zdravil Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezanih imen za vloženo indikacijo neugodno;
English: Moreover, it was considered inappropriate for the MAH to refer to data from another GH product to claim the same indication since Norditropin was not authorised as a similar biological medicinal product.
Slovenian: Za neprimerno so štele tudi, da se imetnik dovoljenja za promet sklicuje na podatke drugega zdravila, ki vsebuje rastni hormon, da bi uveljavil enako indikacijo, saj zdravilo Norditropin ni bilo odobreno kot podobno biološko zdravilo.
English: In this study the dose of Norditropin administered was chosen at the discretion of the physician and adjusted accordingly during the treatment period (the mean dose was 0.03 mg/kg/day).
Slovenian: Uporabljeni odmerek zdravila Norditropin je v tej študiji izbral zdravnik po lastni presoji in ga v času zdravljenja ustrezno prilagodil (povprečni odmerek je bil 0,03 mg/kg/dan).
English: Lean body mass increased by 9.1% from baseline to last observation.
Slovenian: Mršava telesna masa se je od začetka do zadnjega opazovanja povečala za 9,1 %.
English: The estimated gain in HSDS was 1.1 to last observation.
Slovenian: Ocenjeno povečanje HSDS je znašalo 1,1 do zadnjega opazovanja.
English: HSDS improved from a baseline mean of -0.3 to 1.1 at last observation.
Slovenian: HSDS se je izboljšala z izhodiščne srednje vrednosti -0,3 na 1,1 ob zadnjem opazovanju.
English: In addition, not only improvement of growth but also improvement of body composition is part of the indication of Norditropin in PWS.
Slovenian: Del indikacije zdravila Norditropin pri PWS je poleg izboljšanja telesne višine tudi izboljšanje sestave telesa.
English: the CHMP has recommended the refusal of the variation of the Marketing Authorisations for Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro and associated names (see Annex I).
Slovenian: je Odbor za zdravila za uporabo v humani medicini priporočil zavrnitev spremembe dovoljenj za promet z zdravili Norditropin SimpleXx, Norditropin NordiFlex, Norditropin FlexPro in povezanimi imeni (glejte Prilogo I).
English: When standardised to the normal population, an estimated mean gain in HSDS of 0.7 was obtained after 1 year of Norditropin treatment in short children with PWS.
Slovenian: Ocenjeno povprečno povečanje HSDS v vrednosti 0,7, standardizirano na normalno populacijo, je bilo doseženo po 1 letu zdravljenja z zdravilom Norditropin pri otrocih nizke rasti s PWS.
English: When standardised to the PWS population, an estimated mean gain in HSDS of 0.9 was obtained after 1 year of Norditropin treatment in short children with PWS.
Slovenian: Ocenjeno povprečno povečanje HSDS v vrednosti 0,9, standardizirano na populacijo s PWS, je bilo doseženo po 1 letu zdravljenja z zdravilom Norditropin pri otrocih nizke rasti s PWS.
English: In addition, it is not considered acceptable to refer to the prospective data obtained with another GH product in order to claim the same indication with the same dose regimen, in view of the legal basis of the marketing authorisation of Norditropin, i.e.
Slovenian: Poleg tega je ob upoštevanju pravne podlage za izdajo dovoljenja za promet z zdravilom Norditropin, tj. člena 8(3) Direktive 2001/83/ES, neprimerno, da se imetnik dovoljenja za promet sklicuje na prospektivne podatke, pridobljene za drugo zdravilo, ki vsebuje rastni hormon, da bi uveljavil enako indikacijo z enakim režimom odmerjanja.
English: The children were naïve to GH therapy at the time of first dose of Norditropin.
Slovenian: V času prvega odmerka zdravila Norditropin otroci še niso bili izpostavljeni zdravljenju z rastnim hormonom.
English: Date of first authorisation: 25 July 2008 Date of latest renewal: 21 June 2013
Slovenian: Datum prve odobritve: 25. julij 2008 Datum zadnjega podaljšanja: 21. junij 2013
English: This might cause you to move or cough at the end of the operation
Slovenian: Zaradi tega se boste morda tudi premaknili ali zakašljali ob koncu operacije.
English: Gender: No gender differences were observed.
Slovenian: Spol: Niso opazili nobenih razlik med spoloma.
English: CV=coefficient of variation
Slovenian: KV=koeficient variacije
English: An increased risk of bleeding cannot be excluded in patients:
Slovenian: Povečanega tveganja za krvavitve ni mogoče izključiti pri bolnikih:
English: You may still be given Bridion, but you need to discuss it first.
Slovenian: Morda vam bo kljub temu dal zdravilo Bridion, vendar se morata najprej pogovoriti o tem.
English: Information on healthy volunteers:
Slovenian: Podatki o zdravih prostovoljcih:
English: From a microbiological point of view, the diluted product should be used immediately.
Slovenian: Z mikrobiološkega stališča je treba razredčeno zdravilo uporabiti takoj.
English: Storage will be handled by healthcare professionals.
Slovenian: Za shranjevanje bodo poskrbeli zdravstveni delavci.
English: A mass balance study demonstrated that > 90% of the dose was excreted within 24 hours.
Slovenian: Študija masnega ravnotežja je pokazala, da se > 90 % odmerka zdravila izloči v 24 urah.
English: Mean Predicted PK parameters (CV%)
Slovenian: Povprečje predvidenih PK parametrov (KV %)
English: Bradycardia may occasionally lead to cardiac arrest.
Slovenian: Bradikardija lahko občasno vodi do srčnega zastoja.
English: Patients with severe hepatic impairment should be treated with great caution.
Slovenian: Bolnike s hudo jetrno okvaro je treba zdraviti zelo previdno.
English: Children and adolescents This medicine is not recommended for infants less than 2 years of age.
Slovenian: Otroci in mladostniki Uporaba tega zdravila ni priporočljiva za dojenčke, mlajše od 2 let.
English: The above mentioned interactions for adults and the warnings in section 4.4 should also be taken into account for the paediatric population.
Slovenian: Zgoraj omenjene interakcije pri odraslih bolnikih in opozorila iz poglavja 4.4 morate torej upoštevati tudi pri pediatričnih bolnikih.
English: Demographics
Slovenian: Demografija
English: Toremifene:
Slovenian: Toremifen:
English: Minimum waiting time
Slovenian: Minimalni časovni presledek
English: 5 minutes
Slovenian: 5 minut
English: Children and adolescents:
Slovenian: Otroci in mladostniki:
English: Effects on blood tests
Slovenian: Vpliv na krvne preiskave
English: The same dose recommendations as for adults should be followed.
Slovenian: Pri njih je treba upoštevati enaka priporočila kot za vse odrasle bolnike.