natgillin/translations-raw huggingface dataset:
*Tmax expressed as time since start of ~4 hour infusion and presented as median [min, max], and occurred at the first sampling timepoint post infusion
*tmax izražen kot čas od začetka ~4-urnega infundiranja in predstavljen kot mediana [min, maks], ki se je pojavil od prve časovne točke vzorčenja po infundiranju
Study 190-203 is an ongoing open label clinical study evaluating the safety and efficacy in patients from birth to 18 years of age.
Študija 190-203 je potekajoča odprta klinična študija, v kateri ocenjujejo varnost in učinkovitost pri bolnikih od rojstva do 18 leta starosti.
If you or your child has a history of heart problems, your doctor or nurse will monitor your heart activity during each infusion.
Če imate vi ali vaš otrok težave s srcem v anamnezi, bosta zdravnik ali medicinska sestra aktivnost srca spremljala med vsakim infundiranjem.
Patients with advanced CLN2 disease and newborns may have decreased integrity of the blood-brain barrier.
Bolniki z napredovalo CLN2 in novorojenčki imajo morda zmanjšano integriteto krvno-možganske pregrade.
However, these signs may also occur in the context of device-related infections.
Ti znaki se lahko pojavijo tudi ob okužbah, povezanih s pripomočkom.
Talk to your doctor if you have any questions about your device.
Posvetujte se s svojim zdravnikom, če imate vprašanja glede pripomočka.
The medicine and solution will be given over about 2 to 4 hours and 30 minutes according to your or your child's dose.
Zdravilo in raztopina se dajeta v razponu od 2 ur do 4 ur in 30 minut, odvisno od vašega ali otrokovega odmerka.
4.7 Effects on ability to drive and use machines
4.7 Vpliv na sposobnost vožnje in upravljanje strojev
• Program the pump alarms to sound at the most sensitive settings for pressure, rate, and volume limits.
• Programirajte alarme črpalke na najbolj občutljivo nastavitev omejitev za tlak, hitrost in količino.
Your doctor will check for abnormal heart electrical activities (ECG) every 6 months.
Zdravnik bo vsakih 6 mesecev preveril morebitne nenormalne električne aktivnosti srca (EKG).
- If you or your child currently has signs of a device infection or problems with the device.
- Če imate vi ali vaš otrok trenutno znake okužbe pripomočka ali težav s pripomočkom.
Your doctor may decide to continue treatment once the device infection or problems are resolved.
Vaš zdravnik se lahko odloči za nadaljevanje zdravljenja, ko se okužba pripomočka ali težave razrešijo.
CLN2 patients with ventriculo-peritoneal shunts.
Bolniki CLN2 z ventrikulo-peritonealnimi šanti.
0 No intelligible words or vocalizations.
Ni razumljivih besed ali oglašanj.
Your doctor will discuss whether Brineura treatment is right for you or your child.
Zdravnik se bo z vami pogovoril, ali je zdravljenje z zdravilom Brineura za vas ali vašega otroka primerno.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Zaradi pomanjkanja študij o kompatibilnosti zdravila ne smemo mešati z drugimi zdravili.
• Two single-use syringes compatible with the pump equipment.
• Dve injekcijski brizgi za enkratno uporabo, združljivi z opremo črpalke.
In patients less than 2 years of age, lower doses are recommended, see paediatric population section.
Pri bolnikih, starih manj kot 2 leti, se priporočajo manjši odmerki, glejte poglavje Pediatrična populacija.
Both patients have received 8 infusions and the overall safety profile of Brineura in these younger patients appears consistent with the safety profile observed in older children.
Oba bolnika prejela 8 infuzij in splošni profil varnosti zdravila Brineura pri teh mlajših bolnikih se zdi skladen s profilom varnosti, ki so ga ugotovili pri starejših otrocih.
Treatment may be interrupted if the device needs to be replaced or until the infection clears.
Zdravljenje se lahko prekine, če je treba pripomoček zamenjati ali dokler okužba ne izzveni.
Do not thaw or warm vials any other way.
Vial ne odtajajte in grejte na noben drug način.
No fertility studies with cerliponase alfa have been conducted in animals or humans.
Študij plodnosti s cerliponazo alfa pri živalih ali ljudeh niso izvedli.
Motor
Motorika
No correlations were found between higher ADA titres and reductions in efficacy measurements.
Korelacij med višjimi titri ADA in zmanjšanjem izmerjene učinkovitosti niso ugotovili.
200 (first 4 doses) 300 (subsequent doses)
200 (prvi 4 odmerki) 300 (poznejši odmerki)
Figure 1: Infusion System Set Up
Slika 1: Nastavitev infuzijskega sistema
The posology proposed in children below 2 years has been estimated based on brain mass.
Odmerjanje, predlagano pri otrocih, starih manj kot 2 leti, je bilo ocenjeno na podlagi možganske mase.
The device helps the medicine to reach a specific part of the brain.
pomočjo pripomočka zdravilo doseže določen del v možganih.
Symptoms resolved over time or with administration of antipyretics, antihistamines and/or glucocorticosteroids.
Simptomi so izzveneli sčasoma ali z dajanjem antipiretikov, antihistaminikov in/ali glukokortikosteroidov.
Tmax*, hr
tmax*, ure
In patients less than 3 years of age the recommended dose is in accordance with the posology used in the ongoing clinical study 190-203, see section 5.1.
Pri bolnikih, starih manj kot 3 leta, je priporočeni odmerek v skladu z odmerjanjem, ki ga uporabljajo v potekajoči klinični študiji 190-203, glejte poglavje 5.1.
Convulsions resolved with standard anti-convulsive therapies, and did not result in discontinuation of Brineura treatment.
Konvulzije so izzvenele s standardnimi antikonvulzivnimi zdravljenji in niso povzročile prekinitve zdravljenja z zdravilom
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before treatment with this medicine.
Nosečnost, dojenje in plodnost Če ste noseči ali dojite, menite, da bi lahko bili noseči, ali načrtujete zanositev, se posvetujte z zdravnikom, preden zdravljenjem s tem zdravilom.
Convulsions are a common manifestation of CLN2 disease and are expected to occur in this population.
Konvulzije so pogosta manifestacija CLN2 in njihovo pojavljanje je pri tej populaciji pričakovano.
There is limited data in patients older than 8 years of age.
Podatki za bolnike, starejše od 8 let, so omejeni.
Will have obvious instability, and may have intermittent falls.
Očitna nestabilnost in možni občasni padci.
Upon completion of the infusion, the patient status should be clinically assessed and observation may be necessary for longer periods if clinically indicated, particularly in patients less than 3 years.
Po koncu infuzije je treba klinično oceniti stanje bolnika; morda ga bo treba opazovati dlje časa, če je to klinično indicirano, zlasti pri bolnikih, starih manj kot 3 leta.
However, the results of these studies in dachshund dogs cannot reliably predict human safety, because the regimen of cerliponase alfa infusions was different and highly variable even within the same study due to difficulties with the indwelling catheter system and prominent hypersensitivity reactions.
Vendar pa rezultati teh študij na psu jazbečarju ne morejo z gotovostjo napovedati varnosti pri človeku, saj je bil režim infundiranja cerliponaze alfa drugačen in se je zelo razlikoval tudi v okviru iste študije zaradi težav z vsajenim katetrskim sistemom in izrazitih preobčutljivostnih reakcij.
- If you or your child has had life-threatening allergic reactions to cerliponase alfa or any of the other ingredients of this medicine (listed in section 6), and the reactions continue to happen when cerliponse alfa is given again.
- Če ste vi ali vaš otrok imeli življenje ogrožajočo alergijsko reakcijo na cerliponazo alfa ali katero koli sestavino tega zdravila (navedeno v poglavju 6) in se reakcija ob ponovni uporabi cerliponaze alfa ponovi.
In study 190201, 23 patients were treated for 48 weeks (1 patient withdrew after week 1 due to the inability to continue with study procedures).
V študiji 190-201 je bilo 23 bolnikov zdravljenih 48 tednov (1 bolnik je po 1. tednu prekinil sodelovanje zaradi nezmožnosti nadaljevanja s študijskimi postopki).
Findings from studies 190-201 and 190-202 were compared with a natural history control group that included patients that satisfied the inclusion criteria for studies 190-201 and 190-202.
Izsledke iz študij 190-201 in 190-202 so primerjali s kontrolno skupino z naravnim potekom, ki je vključevala bolnike, ki so izpolnili vključitvene kriterije za študiji 190-201 in 190-202.
This disease model primarily served to investigate the pharmacodynamic and pharmacokinetic properties of cerliponase alfa, but also aimed to evaluate the toxicity of the substance.
Model bolezni je bil primarno namenjen proučevanju farmakodinamičnih in farmakokinetičnih lastnosti cerliponaze alfa, pa tudi oceni toksičnosti učinkovine.
Pharmacotherapeutic group: other alimentary tract and metabolism products, enzymes, ATC code: A16AB17.
Farmakoterapevtska skupina: druga zdravila za bolezni prebavil in presnove, encimi, oznaka ATC: A16AB17.
In order to further evaluate the treatment effectiveness as a delay in progression of CLN2 motor-language clinical sale and to further evaluate the safety and tolerability of cerliponase alfa, the MAH will submit the results of study 190-203 including at least 5 patients below the age of 2 years.
Za nadaljnjo oceno učinkovitosti zdravljenja kot zakasnitev napredovanja CLN2 na klinični lestvici za ocenjevanje motorično-govornih spretnosti in nadaljnjo oceno varnosti in prenašanja cerliponaze alfa, bo imetnik dovoljenja za promet z zdravilom predložil rezultate študije 190-203, v katero bo vključenih vsaj 5 bolnikov, mlajših od 2 let.
Patients who experienced moderate hypersensitivity adverse events were tested for drug-specific IgE and found to be negative.
Bolnike, ki so imeli zmerne preobčutljivostne neželene učinke, so testirali za IgE, specifičen za zdravilo, in ugotovili, da so negativni.
Your doctor may lower the dose or the speed of the infusion based on your response during the treatment.
Zdravnik lahko odmerek ali hitrost infundiranja zmanjša na podlagi vašega odziva med zdravljenjem.
After long periods of use, the access device may need to be replaced and will be determined by your doctor.
Po daljšem času uporabe je treba pripomoček za dostop zamenjati, kar določi zdravnik.
The inline filter may be integral to the infusion set.
Filter v liniji je lahko integriran v infuzijski set.
Each domain encompasses scores of 3 (grossly normal) to 0 (profoundly impaired), for a total possible score of 6, with unit decrements representing milestone events in the loss of previously attained functions of ambulation and speech.
Vsaka domena je zajemala ocene od 3 (večinoma normalno) do 0 (skrajno okvarjeno), pri čemer je bila najvišja možna skupna ocena 6, s pojemki enot, ki so predstavljali mejnik dogodkov pri izgubi predhodno pridobljene funkcije mobilnosti in govora.
The observed treatment effect was considered clinically meaningful in light of the natural history of untreated CLN2 disease.
Opaženi učinek zdravljenja se obravnava kot klinično pomemben v luči naravnega poteka nezdravljene CLN2.
frequency convention defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Opaženi neželeni učinki so navedeni spodaj po organskih sistemih in pogostnosti, skladno z opredelitvijo pogostnosti po MedDRA, kot: zelo pogosti (≥1/10), pogosti (≥1/100 do <1/10), občasni (≥1/1.000 do <1/100), redki (≥1/10.000 do <1/1.000), zelo redki (<1/10.000), neznana pogostnost (ni mogoče oceniti iz razpoložljivih podatkov).
The European Medicines Agency has deferred the obligation to submit the results of studies with Brineura in one or more subsets of the paediatric population in CLN2 (see section 4.2 for information on paediatric use).
Evropska agencija za zdravila je začasno odložila zahtevo za predložitev rezultatov študij z zdravilom Brineura za eno ali več podskupin pediatrične populacije s CLN2 (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
Cerliponase alfa is a recombinant form of human tripeptidyl peptidase-1 (rhTPP1).
Mehanizem delovanja Cerliponaza alfa je rekombinantna oblika humane tripeptidil-peptidaze-1 (rhTPP1).
• Two single-use hypodermic syringe needles, (21 G, 25.4 mm).
• Dve hipodermični igli za brizgo za enkratno uporabo, (21 G, 25,4 mm).
6.7 (first 4 doses) 10 (subsequent doses)
6,7 (prvi 4 odmerki) 10 (poznejši odmerki)
Cerliponase alfa is taken up by target cells and translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor).
Ciljne celice cerliponazo alfa privzemajo in prenesejo do lizosomov s pomočjo receptorja CI-MPR (Cation Independent Mannose-6Phosphate Receptor) (znan tudi kot receptor M6P/IGF2).
Mean (SD)
Povprečje (SD)
Material degradation of the intracerebroventricular access device reservoir occurs after long periods of use according to preliminary results of benchtop testing and as observed in clinical trials with approximately 4 years of use.
Degradacija materiala rezervoarja pripomočka za intracerebroventrikularni dostop se pojavi po daljšem obdobju uporabe v skladu s predhodnimi rezultati laboratorijskega testiranja in kot je bilo ugotovljeno v kliničnih preskušanjih po približno 4 letih uporabe.
Adverse reactions are presented in order of decreasing seriousness.
Neželeni učinki so navedeni po padajoči resnosti.
A total of 15 patients out of 23 (65%) had no overall decline in CLN2 score, irrespective of baseline score, and 2 of these 15 patients increased their score by one point during the treatment period.
Skupaj 15 od 23 bolnikov (65 %) ni imelo skupnega upada ocene CLN2, neodvisno od izhodiščne ocene, pri 2 od teh 15 bolnikov pa se je ocena v obdobju zdravljenja zvišala za eno točko.
The activated proteolytic enzyme (rhTPP1) cleaves tripeptides from the N-terminus of the target protein with no known substrate specificity.
Aktivirani proteolitični encim (rhTPP1) cepi tripeptide na N-koncu ciljne beljakovine brez znane specifičnosti za substrat.
From a microbiological point of view, open vials or medicinal product held in syringes should be used immediately.
Z mikrobiološkega vidika je treba odprte viale ali zdravilo v injekcijskih brizgah uporabiti takoj.
Continuation of long-term treatment should be subject to regular clinical evaluation whether the benefits are considered to outweigh the potential risks to individual patients.
V nadaljevanju dolgotrajnega zdravljenja je treba s kliničnim ocenjevanjem redno preverjati, ali so koristi zdravljenja večje od možnih tveganj za posamezne bolnike.
Prior to the launch of BRINEURA in each Member State (MS), the Marketing Authorisation Holder (MAH) must agree about the content and format of the educational materials, including communication media, distribution modalities, and any other aspects of the programme, with the National Competent Authority (NCA).
Pred prihodom zdravila BRINEURA na trg v vsaki državi članici se mora imetnik dovoljenja za promet z zdravilom s pristojnim nacionalnim organom dogovoriti o vsebini in obliki izobraževalnega gradiva, vključno s sredstvi obveščanja, načinom razdeljevanja in vsemi drugimi vidiki programa.
All pharmacokinetic parameters were similar following the initial infusion on Day 1 and following infusions at Week 5 and Week 13, indicating no apparent accumulation or time dependent PK of cerliponase alfa in CSF or plasma when administered at of dose of 300 mg once every other week.
Vsi farmakokinetični parametri so bili podobni po začetni infuziji na 1. dan in po infuzijah v 5. tednu in 13. tednu, kar kaže, da ni očitnega kopičenja ali od časa odvisne FK cerliponaze alfa v CSL ali plazmi, če se daje v odmerku 300 mg enkrat vsak drugi teden.
Cerliponase alfa is a proteolytic inactive proenzyme (zymogen) that is activated in the lysosome.
Cerliponaza alfa je proteolitični inaktivni proencim (cimogen), ki se aktivira v lizosomu.
In cardiac normal patients, regular 12-lead ECG evaluations should be performed every 6 months.
Pri bolnikih z normalnim srcem je treba redno ocenjevanje z EKG-jem z 12 kanali izvajati vsakih 6 mesecev.
You or your child may get problems with the implanted device used during treatment with Brineura (see section 4 “Possible side effects”), including infection or a fault in the device.
Vi ali vaš otrok imate lahko težave z vsajenim pripomočkom, ki se uporablja med zdravljenjem z zdravilom Brineura (glejte poglavje 4 "Možni neželeni učinki"), vključno z okužbo ali okvaro pripomočka.
Hypersensitivity reactions were reported in 14 out of 24 patients (58%) treated with Brineura.
O preobčutljivostnih reakcijah so poročali pri 14 od 24 bolnikov (58 %), zdravljenih z zdravilom
Your doctor may give you or your child medicines, such as antipyretics to reduce fever or antihistamines to treat allergic reactions before each treatment with Brineura to reduce side effects that can occur during or shortly after treatment.
Zdravnik lahko vam ali vašemu otroku da zdravila, kot so antipiretiki za znižanje telesne temperature ali antihistaminiki za zdravljenje alergijskih reakcij, pred vsakim zdravljenjem z zdravilom Brineura za zmanjšanje neželenih učinkov, ki se lahko pojavijo med zdravljenjem ali tik po njem.
Chemical and physical in-use stability has been demonstrated for up to 12 hours at room temperature (19-25°C).
Kemična in fizikalna stabilnost za uporabo je bila dokazana za obdobje do 12 ur pri sobni temperaturi (19 °C do 25 °C).
Posology was based upon analysis of differences in brain mass values for children less than 3 years of age.
Odmerjanje je temeljilo na analizi razlik v vrednosti možganske mase za otroke, stare manj kot 3 leta.
Brineura must be administered using aseptic technique to reduce the risk of infection.
Za dajanje zdravila Brineura je treba uporabiti aseptično tehniko, da se zmanjša tveganje za okužbe.
Overall, 23 (96%) subjects who received cerliponase alfa experienced an event that mapped to the Convulsions Standardized MedDRA Query.
Skupaj je 23 (96 %) oseb, ki so prejemale cerliponazo alfa, doživelo dogodek, ki je bil mapiran v standardizirano MedDRA poizvedbo za konvulzije (Convulsions Standardized MedDRA
A length of 150 to 206 cm (not to exceed 400 cm) and an inner diameter of 0.1 cm is recommended.
Priporoča se dolžina od 150 do 206 cm (ne več kot 400 cm) in notranji premer 0,1 cm. • Potreben je 0,2 µm filter v liniji.
They are also responsible for disposing of any unused Brineura properly.
Odgovorna sta tudi za pravilno odstranitev neporabljenega zdravila Brineura.
The flushing solution may contain particles that dissolve when the vial is fully thawed.
Raztopina za izpiranje lahko vsebuje delce, ki se raztopijo, ko je viala do konca odtaljena.
If immediate use is not possible, unopened vials of Brineura or flushing solution should be stored at 2-8°C and used within 24 hours.
Če vsebine ne morete uporabiti takoj, lahko neodprte viale zdravila Brineura ali raztopine za izpiranje shranite pri 2-8 °C, nato pa ju porabite v 24 urah.
Results from the natural history control group demonstrate CLN2 disease is a rapidly progressive neurodegenerative disease with predictable decline in motor and language function with an estimated mean rate of decline in the CLN2 score of 2 points per 48 weeks.
Rezultati iz kontrolne skupine z naravnim potekom kažejo, da je CLN2 hitro napredujoča nevrodegenerativna bolezen z napovedljivim upadom motorične in govorne funkcije z ocenjeno povprečno stopnjo upada ocene za CLN2 2 točki na 48 tednov.
CSF (N=17) Mean (SD)
CSL (N = 17)
Withdraw 0.5 ml to 1 ml of CSF to check patency of the intracerebroventricular access device.
Izvlecite 0,5 ml do 1 ml CSL, da preverite prehodnost pripomočka za intracerebroventrikularni dostop.
There are no data on the presence of cerliponase alfa in human milk, the effects of cerliponase alfa on the breastfed child, or the effects of cerliponase alfa on milk production.
Podatkov o prisotnosti cerliponaze alfa v materinem mleku pri ljudeh, učinkih cerliponaze alfa na dojenega otroka ali učinkih cerliponaze alfa na nastajanje mleka ni.
Brineura has not been given to patients with advanced disease at the start of treatment or in children younger than 2 years of age.
Zdravila Brineura niso dajali bolnikom z napredovalo boleznijo ob začetku zdravljenja ali otrokom, mlajšim od 2 let.
The access devices were replaced and patients resumed treatment with Brineura.
Pripomoček za dostop je bil zamenjan in bolniki so nadaljevali zdravljenje z zdravilom Brineura.
Electrocardiogram (ECG) monitoring during infusion should be performed in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may develop conduction disorders or heart disease.
Spremljanje z elektrokardiogramom (EKG) med infundiranjem je treba izvajati pri bolnikih, pri katerih so v anamnezi bradikardija, motnje prevajanja ali strukturna bolezen srca, saj se lahko pri nekaterih bolnikih s CLN2 pojavijo motnje prevajanja ali bolezen srca.
The most commonly reported convulsion events include seizure, epilepsy and generalized tonic-clonic seizure.
Najpogostejši poročani dogodki konvulzij vključujejo epileptični napad, epilepsijo in generaliziran tonično-klonični napad.
Dispose of the infusion components, needles, unused solutions and other waste materials in accordance with local requirements.
Komponente za infundiranje, igle, neporabljeno raztopino in druge odpadne materiale odstranite v skladu z lokalnimi zahtevami.
Table 3: CLN2 Clinical Rating Scale
Preglednica 3: Klinična ocenjevalna lestvica CLN2
Brineura contains sodium:
Zdravilo Brineura vsebuje natrij:
If the infusion is interrupted due to a hypersensitivity reaction, it should be restarted at approximately onehalf the initial infusion rate at which the hypersensitivity reaction occurred.
Pri prekinitvi infundiranja zaradi preobčutljivostne reakcije je treba nadaljevati s približno polovično začetno hitrostjo infundiranja, pri kateri se je pojavila preobčutljivostna reakcija.
Cerliponase alfa is a recombinant human protein and systemic exposure is limited due to intracerebroventricular administration, therefore interactions between cerliponase alfa and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur.
Cerliponaza alfa je rekombinantni humani protein in sistemska izpostavljenost je omejena zaradi intracerebroventrikularnega dajanja, zato interakcije med cerliponazo alfa in zdravili, ki jih presnavljajo encimi citokroma P450, niso verjetne.
Treatment should be based on the benefits and risks to the individual patient as assessed by the physician.
Zdravljenje mora temeljiti na zdravnikovi oceni koristi in tveganj za posamičnega bolnika.
The signs and symptoms of device-related infections may not be apparent, therefore, CSF samples should routinely be sent for testing to detect subclinical device infections.
Znaki in simptomi okužb, povezanih s pripomočkom, morda ne bodo očitni, zato je treba vzorce CSL rutinsko pošiljati na testiranje za odkrivanje subkliničnih okužb pripomočka.
Life-threatening anaphylactic reaction to the active substance or to any of the excipients listed in section 6.1, if re-challenge is unsuccessful (see section 4.4).
Življenje ogrožajoča anafilaktična reakcija na učinkovino ali katero koli pomožno snov, navedeno v poglavju 6.1, če ponovna uporaba ni uspešna (glejte poglavje 4.4).
Your doctor will check your or your child's heart rate, blood pressure, respiratory rate, and temperature before, during, and after treatment.
Zdravnik bo preveril vaš ali otrokov srčni utrip, krvni tlak, hitrost dihanja in temperaturo pred zdravljenjem, med njim in po njem.
The most common manifestations included pyrexia with vomiting, pleocytosis, or irritability, which are inconsistent with classic immune mediated hypersensitivity.
Najpogostejše manifestacije so vključevale pireksijo z bruhanjem, pleocitozo ali razdražljivost, kar je neskladno s klasično preobčutljivostjo, pri kateri posreduje imunski sistem.