natgillin/translations-raw huggingface dataset:
Avelox 400 mg - Filmtabletten 400 mg Film-coated tablet
Avelox 400 mg - Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
Netherlands Bayer HealthCare AG 51368 Leverkusen
Nizozemska Bayer HealthCare AG 51368 Leverkusen
Luxembourg Bayer Healthcare AG 51368 Leverkusen
Luksemburg Bayer Healthcare AG 51368 Leverkusen
Actira 400 mg film coated tablets400 mg Film-coated tablet
Actira 400 mg film coated tablets400 mg Filmsko obložena tableta Peroralna uporaba
Actimax 400 mg Filmtabletten 400 mg Film-coated tablet
Actimax 400 mg Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
Belgium Bayer AG 51368 Leverkusen Germany
Portugalska Bayer AG 51368 Leverkusen Nemčija
Actira 400 mg - Filmtabletten 400 mg Film-coated tablet
Actira 400 mg - Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
Octegra 400 mg - Filmtabletten 400 mg Film-coated tablet
Octegra 400 mg - Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
Actira 400 mg Filmtabletten 400 mg Film-coated tablet
Actira 400 mg Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
Moxafloxacin hydrochloride
Moksifloksacin Octegra
Octegra 400 mg Filmtabletten 400 mg Film-coated tablet
Octegra 400 mg Filmtabletten 400 mg Filmsko obložena tableta Peroralna uporaba
The response to the third part (iii) has been provided separately.
Odgovor na tretji del (iii) je podal ločeno.
According with Coupe A.J.
V skladu s Coupe A.J.
Absence of a Formulation Difference
Odsotnost razlike med formulacijama
During the course of the study, 80 adverse events were reported.
Med študijo so poročali o 80 neželenih dogodkih.
Safety results
Rezultati glede varnosti
The Applicant, given the degree of overlap between the first two parts of the question [(i) and (ii)] combined its response to these.
Predlagatelj je glede na stopnjo prekrivanja prvih dveh delov vprašanja [(i) in (ii)] podal skupen odgovor na ti dve vprašanji.
The samples were immediately stored at -25°C and transferred to the analytical facility.
Vzorci so bili takoj shranjeni pri -25 °C in preneseni v analitični laboratorij.
In conclusion, both results were considered to be fully acceptable.
Če povzamemo, veljata oba rezultata za povsem sprejemljiva.
All the available data were included without any imputation or extrapolation.
Vsi razpoložljivi podatki so bili vključeni brez imputacije ali ekstrapolacije.
The information on the originator product has been clarified to a satisfactory extent.
Informacije o originatorskem zdravilu so bile zadostno pojasnjene.
The detailed results of the long-term stability data of human samples were given.
Podani so bili podrobni rezultati podatkov o dolgoročni stabilnosti človeških vzorcev.
Initial Bioequivalence Studies
Začetni bioekvivalenčni študiji
For long-term stability a reduction was seen in pantoprazole content of between 6-8% of the nominal content, which was considered acceptable.
Pri preskusu dolgoročne stabilnosti je bilo opaženo zmanjšanje vsebnosti pantoprazola za 6-8 % nazivne vsebnosti, kar je veljalo za sprejemljivo.
The wash-out phase was 7 days.
Premor je trajal 7 dni.
All tests achieved satisfactory results with only small deviations.
Vsi preskusi so izkazali zadovoljive rezultate z le majhnimi odstopanji.
Population studied
Proučevana populacija
Main Analysis
Glavna analiza
All tests revealed acceptable results.
Vsi preskusi so izkazali sprejemljive rezultate.
There were no deaths, and no serious or other significant adverse events in the course of the study.
Med študijo ni bilo primerov smrti, niti resnih ali drugih pomembnih neželenih dogodkov.
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF PANTOPRAZOLE BLUEFISH AND ASSOCIATED NAMES (SEE ANNEX I)
SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA PANTOPRAZOLE BLUEFISH IN Z NJIM POVEZANIH IMEN (GLEJTE DODATEK I)
No extrapolation or imputation has been used in the statistical analysis.
V statistični analizi ni bila uporabljena ekstrapolacija ali imputacija.
The documentation of the analytical methods comprised an Analytical Report and a Re-validation report.
Dokumentacija analitičnih metod je vključevala analitično poročilo in poročilo o revalidaciji.
The Applicant submitted analytical reports for the studies.
Predlagatelj je predložil analitična poročila k študijam.
The mean ratio “test over reference” was calculated as 85.6 with 90 % confidence intervals of 77.6-95.6 %.
Povprečno razmerje med „testno in referenčno vrednostjo“ je bilo izračunano kot 85,6 z 90 % intervali zaupanja od 77,6 do 95,6 %.
The Applicant submitted an additional validation study.
Predlagatelj je predložil dodatno validacijsko študijo.
If a reliable estimate of terminal half-life is necessary this should be obtained by collecting at least three to four samples during the terminal log linear phase.
Če je potrebna zanesljiva ocena končnega razpolovnega časa, jo je mogoče pridobiti z zbiranjem najmanj treh do štirih vzorcev med končno logaritemsko-linearno fazo.
et al. (1991) food may delay gastric emptying up to 10-11 hours and thus can influence the timing of the absorption of orally administered drugs.
et al. (1991) lahko hrana odloži praznjenje želodca do 10-11 ur in s tem vpliva na čas absorpcije peroralno dajanih zdravil.
The CHMP acknowledged the analysis of the whole sample including all cases and concluded that both of the formulations studied can be considered as bioequivalent.
CHMP je potrdil analizo celotnega vzorca vključno z vsemi primeri in sklenil, da je obe proučevani formulaciji mogoče šteti kot bioekvivalentni.
SE-111 23 Stockholm Sweden
SE-111 23 Stockholm Švedska
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES
DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVILA, POTI UPORABE ZDRAVILA, PREDLAGATELJEV V DRŽAVAH ČLANICAH
The change of name was caused by company takeover.
Vzrok za spremembo naziva je bil prevzem družbe.
This, in general, is achieved if the AUC derived from measurements is at least 80 % of the AUC extrapolated to infinity.
To je v splošnem zagotovljeno, če znaša AUC, ki je izpeljana iz meritev, najmanj 80 % AUC, ekstrapolirane do neskončnosti.
• A case will be considered to be an outlier if at least one of the following conditions apply: - There is complete or almost complete lack of absorption of the drug (AUClast is less than 10 % of the mean values of the corresponding formulation) - If T-max is >12 h
• vrednost bo veljala za osamelca, če je izpolnjen vsaj eden od naslednjih pogojev: - popolna ali skoraj popolna odsotnost absorpcije zdravila (AUClast je pod 10 % povprečnih vrednosti pripadajoče formulacije); - če je T-maks >12 ur.
A period of 15 hours was consequently deemed to be suitable for quantification of at least 80 % of the total AUC, as recommended in the guidelines.
Obdobje 15 ur je tako veljalo za ustrezno za kvantifikacijo najmanj 80 % skupnega obsega AUC, kot priporočajo smernice.
The CHMP found satisfactory justifications regarding the study design in respect to:
Odbor CHMP je pridobil zadovoljive utemeljitve v zvezi z zasnovo študije glede:
Sampling Schedule
Urnik vzorčenja
The observation period of 30 hours exceeded the minimal requirement for studies with pantoprazole, which is considered to be 24 hours.
Opazovano obdobje 30 ur je presegalo minimalno zahtevo za študije s pantoprazolom, kjer znaša 24 ur.
The Applicant answered that a less strict requirement may apply for pantoprazole and submitted a report on the expected clinical relevance of the delayed absorption of pantoprazole observed in the study 2009-2106.
Predlagatelj je odgovoril, da utegne za pantoprazol veljati manj stroga zahteva, in predložil poročilo o pričakovanem kliničnem pomenu odložene absorpcije pantoprazola, ki je bila opažena v študiji 2009-2106.
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR POSITIVE OPINION
DODATEK II ZNANSTVENI ZAKLJUČKI IN PODLAGA ZA POZITIVNO MNENJE
The CHMP acknowledged that in and exclusion criteria, as well as subjects included, number and type of protocol deviations were considered acceptable.
CHMP je menil, da so merila za vključitev in izključitev ter vključene osebe, število in vrsta odstopanj od protokola sprejemljivi.
All of them were of mild severity, some adverse events were eventually related to the study medication.
Vsi so bili blagi, nekatere neželene dogodke je bilo na koncu mogoče pripisati proučevanemu zdravilu.
It included the requested data about long-term stability of human plasma samples along with long-term stability data of stock solutions (749 days at -25°C) and auto-sampler stability (122.5 hours at 5°C).
Ta je vključevala zahtevane podatke o dolgoročni stabilnosti vzorcev človeške plazme skupaj s podatki o dolgoročni stabilnosti osnovnih raztopin (749 dni pri -25 °C) in stabilnosti avtomatskega vzorčevalnika (122,5 ur pri 5 °C).
Furthermore a complete analytical certificate (of test and reference product) was provided with all results being compliant with specifications.
Poleg tega je predložil celotno analitično potrdilo (testnega in referenčnega zdravila) za vse rezultate, ki so skladni s specifikacijami.
For Cmax the confidence interval is 77.6-95.6% which is slightly below the acceptance interval (80-125) but the intraindividual variability (2 period 2 sequence design) is higher than 30% (36%), similar to the data reported in the literature for pantoprazole.
Za Cmaks je interval zaupanja 77,6-95,6 %, kar je nekoliko nižje od intervala sprejemljivosti (80-125), vendar je variabilnost med posamezniki (zasnova 2 obdobij in 2 zaporedij) večja od 30 % (36 %), kar je podobno podatkom, ki so navedeni v literaturi za pantoprazol.
The sampling times were extended at the end of the observation period, which seemed to be considering the weaknesses of the previous study.
Časi vzorčenja so bili proti koncu obdobja opazovanja podaljšani, kar je bila šibka točka prejšnje študije.
Based on a terminal elimination half-life of approximately 1 hour, three times the half-life was considered sufficient to cover the elimination of 83 % of the drug, and five times the half-life was considered to allow for almost complete elimination.
Na podlagi končne eliminacijske razpolovne dobe približno 1 ure je bila razpolovna doba trikrat potrjena za zadostno, da zajame eliminacijo 83 % zdravila, petkrat pa za zadostno, da zagotovi skoraj popolno eliminacijo.
Because different batches were used in the previous bioequivalence studies and in the confirmatory one, the Applicant presented comparative dissolution studies at pH 6 and 6.8 for these different batches.
Ker so bile v prejšnjih bioekvivalenčnih študijah in v potrditveni študiji uporabljene različne serije, je predlagatelj predložil primerljive študije raztapljanja pri pH 6 in 6,8 za te različne serije.
The CHMP considered the Applicant's response acceptable.
CHMP je menil, da je odgovor predlagatelja sprejemljiv.
The CHMP considered that the drug intake after breakfast (30 minutes) was sufficiently short.
Odbor CHMP je menil, da je bilo zdravilo dano dovolj zgodaj po zajtrku (30 minut).
The statistical analysis carried out with all the evaluable data for all volunteers was presented as the secondary analysis.
Statistična analiza, ki je bila izvedena z vsemi ocenljivimi podatki za vse prostovoljce, je bila predstavljena kot sekundarna analiza.
In the food-interaction study, the protocol set-out criteria for outliers based on pilot data that defined possible exclusions based on the following:
V študiji medsebojnega delovanja s hrano so bila v protokolu določena merila za osamelce na podlagi pilotnih podatkov, ki določajo morebitne izključitve na podlagi naslednjega:
The CHMP concluded that the evaluation of the percentage of the extrapolated AUC showed completely appropriate sampling period/sampling times.
CHMP je sklenil, da je ocena odstotka ekstrapoliranega AUC pokazala povsem ustrezno obdobje vzorčenja/čase vzorčenja.
The statistical analysis carried out according to the predefined criteria established in the protocol was presented as the main analysis.
Statistična analiza, ki je bila izvedena v skladu z vnaprej določenimi merili iz protokola, je bila predstavljena kot glavna analiza.
Analytical Methods and Pharmacokinetic Variables
Analitične metode in farmakokinetične spremenljivke
The design of this study was considered inappropriate with respect to the following: - sampling times (should have been at least 24 h) - protocol specifications regarding outliers, and the subsequent exclusion of the outliers.
Zasnova te študije je štela za neustrezno zaradi naslednjega: - časi vzorčenja (morali bi znašati najmanj 24 ur) - specifikacije protokola glede osamelcev in naknadna izključitev osamelcev.
The CHMP concluded that both formulations are equivalent and are therapeutically equivalent and that there is no risk to the clinical management of the patients.
Sklenil je, da sta obe formulaciji enakovredni in terapevtsko enakovredni ter da ne predstavljata tveganja za klinično obravnavanje bolnikov.
In this study, the AUC met the required acceptance interval for bioequivalence (80-125).
V tej študiji je bil AUC v zahtevanem sprejemljivem intervalu za bioekvivalenco (80-125).
(ii) The results of the analyses of the data from the study and why the applicant considers they exclude a formulation difference under fed conditions.
(ii) Rezultati analiz podatkov iz študije in zakaj predlagatelj meni, da ti rezultati izključujejo razliko med formulacijama pri uporabi po zaužitju hrane.
The Applicant showed that the number of patients with an increased % of extrapolated AUC was very low and the variability in both parameters of interest was very high.
Dokazal je, da je bilo število bolnikov s povečanim odstotkom ekstrapoliranega AUC zelo nizko in da je bila variabilnost pri obeh proučevanih parametrih zelo visoka.
The evaluation of the lag-time showed clinically negligible differences regarding the delay of absorption of pantoprazole from the two preparations.
Ocena časovnega zamika je pokazala klinično zanemarljive razlike glede odložitve absorpcije pantoprazola iz dveh pripravkov.
The Applicant pointed out that in defined situations, as for pantoprazole, wider interval (75-133 %) for Cmax may be acceptable “if justified, addressing in particular any safety or efficacy concerns for patients switched between formulations”.
Predlagatelj je opozoril, da utegne biti v določenih situacijah, npr. pri pantoprazolu, sprejemljiv širši interval (75-133 %) za Cmaks „z utemeljitvijo zlasti kakršnih koli zadržkov glede varnosti ali učinkovitosti za bolnike, ki bi jim zamenjali formulacijo“.
All but one of them had either been classified as being clinically not significant or been resolved after the follow-up conducted by the Applicant.
Vse razen ene so bile opredeljene za klinično nepomembne oz. so bile odpravljene po nadaljnjem spremljanju, ki ga je opravil predlagatelj.
There were laboratory abnormalities in the post-study laboratory evaluations for altogether 11 subjects.
Laboratorijske abnormalnosti v laboratorijskih ocenah po zaključku študije so bile opažene pri skupno 11 osebah.
The CHMP concluded that no safety concerns can be derived from the submitted data.
CHMP je sklenil, da iz predloženih podatkov ni mogoče ugotoviti pomislekov glede varnosti.
-the sampling schedule, -the pre-definition of outliers, -the results of the confirmatory study, the dissolution testing, and the result of long term stability of the frozen plasma.
-urnika vzorčenja, -vnaprejšnje določitve osamelcev, -rezultatov potrditvene študije, preskusa raztapljanja in rezultata dolgoročne stabilnosti zamrznjene plazme.
Within the response, the Applicant submitted also the results of the confirmatory bioequivalence study (2009-2106), with sampling period up to 30 hours.
Odgovoru je predlagatelj priložil tudi rezultate potrditvene bioekvivalenčne študije (2009-2106) z obdobjem vzorčenja do 30 ur.
The Applicant presented the population recruited for the confirmatory study.
Predlagatelj je predstavil populacijo, ki je sodelovala v potrditveni študiji.
Fleisher et al, 1996 and de Campos et al. 2007, described that BCS class III drugs present a highly variable pharmacokinetic disposition when taken with a meal due to a reduction of the absorption by simple physical barriers.
Fleisher et al, 1996 in de Campos et al., 2007 so navedli, da imajo zdravila razreda III biofarmacevtskega klasifikacijskega sistema visoko variabilno farmakokinetično dispozicijo, če se dajejo ob obroku, in sicer zaradi zmanjšanja absorpcije zaradi preprostih fizikalnih ovir.
The expert referred to the results of study 2009-2106 and concluded that there was no dose dumping effect, that a delayed start of the antisecretory effect was observed corresponding to the first dose, and subsequent doses had a minor effect on acid suppression.
Strokovnjak se je skliceval na rezultate študije 2009-2106 in ugotovil, da ni bilo učinka sprostitve celotnega odmerka naenkrat, da je bila odložitev antisekretornega učinka opažena po prvem odmerku ter da so imeli naknadni odmerki majhen učinek na zaviranje izločanja kisline.
Pantoprazole is also known to exhibit delayed absorption and increased pharmacokinetic variability when taken with food in some individuals, though the extent of absorption [AUC] is generally considered not to be affected (Radhofer-Welte, 1999, and Fitton and Wiseman and 1996 Andersson).
Pantoprazol je znan tudi po tem, da odloži absorpcijo in poveča farmakokinetično variabilnost pri nekaterih posameznikih ob jemanju s hrano, čeprav na obseg absorpcije [AUC] v splošnem ne vpliva (Radhofer-Welte, 1999, in Fitton in Wiseman ter 1996 Andersson).
The CHMP noted that the expansion of the stated confidence interval for Cmax was not prospectively defined in the study protocol.
CHMP je menil, da razširitev navedenega intervala zaupanja za Cmaks ni bila vnaprej opredeljena v protokolu študije.
The parameters determined, methods used for analysis, and success criteria appear to be standard and are considered acceptable; however the CHMP asked the Applicant to clarify the failed demonstration of bioequivalence regarding the parameter Cmax in the study report.
Opredeljeni parametri, uporabljene metode analize in merila uspešnosti so standardni in sprejemljivi, vendar je CHMP predlagatelja pozval, naj v poročilu o študiji pojasni neuspel dokaz bioekvivalence za parameter Cmaks.
The European Guidelines lay down the criteria for the design of bioavailability and bioequivalence studies (CPMP/EWP/QWP/1401/98).
Evropske smernice določajo merila za zasnovo študije biološke razpoložljivosti in bioekvivalence (CPMP/EWP/QWP/1401/98).
The reference product patients' leaflet was also provided.
Predloženo je bilo tudi navodilo za bolnike za uporabo referenčnega zdravila.
(iii) The results of additional dissolution testing, designed to mimic the gastric environment under fed conditions, and the further support provided by these data together with the discussion of the possible clinical relevance/applicability.
(iii) Rezultati dodatnega preskusa raztapljanja, namenjenega posnemanju želodčnega okolja po zaužitju hrane, in nadaljnja podpora, ki jo zagotavljajo ti podatki, skupaj z obrazložitvijo možnega kliničnega pomena/uporabljivosti.
The Applicant determined the sampling schedule in the study undertaken taking into account the general information from the available published references which in general supported a gastric emptying time range of less than 1 hour to approximately 5 hours where varying intakes of food were involved.
Predlagatelj je opredelil urnik vzorčenja v izvedeni študiji ob upoštevanju splošnih informacij iz razpoložljivih objavljenih referenc, ki v splošnem podpirajo časovni razpon praznjenja želodca od manj kot 1 ure do približno 5 ur, pri čemer se upoštevajo različni vnosi hrane.
Confirmatory Pharmacokinetic Study (study code: 2009-2106)
Potrditvena farmakokinetična študija (koda študije: 2009-2106)
The CHMP considered that the Applicant has complied with the requested response and submitted the data, along with additional data regarding stability of pantoprazole under different conditions.
CHMP je menil, da se je predlagatelj ustrezno odzval na zahtevek in predložil podatke, vključno z dodatnimi podatki o stabilnosti pantoprazola v različnih pogojih.
It was anticipated that outliers would occur with both study groups (test and originator groups) in the fed study.
Pričakovano je bilo, da bodo osamelci prisotni v obeh študijskih skupinah (skupini s testnim in originatorskim zdravilom) v študiji po zaužitju hrane.
The CHMP noted that the results were coherent with the available published information on food interaction of pantoprazole formulations, which describe a potential delayed absorption and an increase in variability.
Odbor CHMP je ugotovil, da se rezultati ujemajo z razpoložljivimi objavljenimi informacijami o medsebojnem delovanju formulacij pantoprazola s hrano, ki opisujejo morebitno odloženo absorpcijo in povečanje variabilnosti.
The Applicant presented the results of a further confirmatory fed study, with a final sampling point of 30 hours.
Predlagatelj je predstavil rezultate nadaljnje potrditvene študije po zaužitju hrane s končno vzorčno točko 30 ur.
the CHMP has recommended the granting of the Marketing Authorisations subject to the conditions, as set out in Annex IV.
CHMP je priporočil odobritev dovoljenja za promet z zdravilom v skladu s pogoji iz Dodatka IV.
The primary analysis was conducted on AUClast and Cmax, using the log-transformed ratios and 90 % Confidence Intervals (CIs).
Primarna analiza je vključevala analizo AUClast in Cmaks z logaritemsko preoblikovanimi razmerji in 90 % intervali zaupanja.
Confirmatory Food Interaction Study -2009-2106
Potrditvena študija medsebojnega delovanja s hrano - 2009-2106
The CHMP concluded, based on the study results, that a difference in PK mechanism for the test and the originator is extremely unlikely given the clear demonstration of bioequivalence in the main analysis and in the secondary (whole analysis with measurable values).
CHMP je na podlagi rezultatov študije sklenil, da je razlika v mehanizmu farmakokinetike pri testnem in originatorskem zdravilu izjemno malo verjetna glede na jasen dokaz bioekvivalence v glavni in v sekundarni analizi (celotna analiza z merljivimi vrednostmi).
The CHMP concluded that the overall study design was acceptable.
CHMP je sklenil, da je celotna zasnova študije sprejemljiva.
As such, the planned sampling schedule should provide an adequate estimation of the Cmax and should cover the plasma concentration time curve sufficiently to provide a reliable estimate of the extent of absorption.
Načrtovani urnik vzorčenja mora podati ustrezno oceno Cmaks in zadostno opredeliti krivuljo plazemske koncentracije v odvisnosti od časa, da se zagotovi zanesljiva ocena obsega absorpcije.
This kinetic alteration appears frequently with pantoprazole and is the basis as to why the Summary of Product Characteristics for Pantoprazole products in the EU state: ‘Swallow whole with water before a meal'.
Ta kinetična sprememba je pogosta pri pantoprazolu, zato je v povzetku glavnih značilnosti zdravil, ki vsebujejo pantoprazol, v EU navedeno: „Pogoltnite cele z vodo pred obrokom“
The CHMP considered that the overall analytical documentation was satisfactory, however retrieved the issue of long-term stability as a major objection and requested the Applicant to submit long-term stability data in the answer to the adopted LoOI.
CHMP je menil, da je celotna analitična dokumentacija zadostna, vendar je izpostavil vprašanje dolgoročne stabilnosti kot glavni zadržek in predlagatelja pozval, naj odgovoru na sprejet seznam izrazitih zadržkov priloži podatke o dolgoročni stabilnosti.
The CHMP adopted also a LoOIs asking the Applicant to further clarify the pending issues.
CHMP je sprejel tudi seznam izrazitih zadržkov, v katerem je predlagatelja pozval, naj podrobneje pojasni še nerešena vprašanja.
The Applicant provided the evaluation of lag-times and % extrapolated AUC.
Predložil je oceno časovnih zamikov in odstotek ekstrapoliranega AUC.
• The rate of outlying cases from the test formulation must be no greater than the reference + 20 %
• delež osamelcev za testno formulacijo ne sme biti večji od referenčnega +20 % (zaokroženo na najbližjo celo vrednost);
Pharmacokinetic Variables
Farmakokinetične spremenljivke