natgillin/translations-raw huggingface dataset:
Der blev således foretaget en indbringelse for Koordinationsgruppen vedrørende gensidig anerkendelse og decentraliserede godkendelsesprocedurer - human (CMD(h)). 
A referral was thus triggered at the Co-ordination Group for Mutual Recognition and Decentralised ProceduresHuman (CMD(h)).
Referenceproduktet i EU er Videx EC, hårde kapsler (200, 250 og 400 mg), der første gang blev godkendt i Det Forenede Kongerige den 19. september 2000. 
The reference product in EU is Videx EC (200, 250 and 400 mg) hard capsules, first authorised in the United Kingdom (UK) on 19 September 2000.
• Klinisk betydning af Cmax med didanosin 
• Clinical significance of Cmax with Didanosine
Den væsentlige betænkelighed, der var rejst af Frankrig og Nederlandene, kunne ikke afklares ved indbringelsen for CMD(h), og sagen blev derfor indbragt for Udvalget for Lægemidler til Mennesker (CHMP). 
The major concern raised by France and the Netherlands could not be solved during the CMD(h) referral and the issue was therefore referred to the Committee for Medicinal Products for Human Use (CHMP).
• udvalget er af den opfattelse, at der er påvist bioækvivalens under fastende betingelser, som er den anbefalede tilstand ved administration af didanosin, 
• The Committee is of the opinion that bioequivalence has been demonstrated under fasting conditions which is the recommended state for administration of didanosine.
Uanset om didanosin indtages med eller uden føde, er den virologiske respons bestemt af den totale eksponering for lægemidlet. 
Irrespective of whether Didanosine is taken with or without food, the virological response is based on the total drug exposure.
De to formuleringer er imidlertid ækvivalente i absorptionsgrad (dvs. AUC). 
However, both formulations are equivalent in terms of extent of absorption (i.e. AUC).
Ansøgeren forelagde litteraturhenvisninger, der viste, at AUC er den vigtigste parameter for virkningen af didanosin 9,10,11,12,13. 
The applicant provided literature references which showed that for the action of Didanosine, AUC is the most important parameter9,10,11,12,13.
Det vedgås, at disse resultater var uden for standardområdet 80125 %, men de var inden for det bredere acceptkriterium på 70-143 %, som kan anvendes for stærkt variable lægemidler. 
It is acknowledged that these results were outside the standard range of 80 - 125%; however these were within the wider acceptance criteria of 70 - 143% which may be used for highly variable drugs.
Relation between plasma concentrations of didanosin and markers of antiviral efficacy in adults with AIDS and AIDS related complex. 
Relation between plasma concentrations of didanosine and markers of antiviral efficacy in adults with AIDS and AIDS related complex.
Den postprandiale undersøgelse blev udført på forlænget tid. 
The fed study was conducted during an extended clock-stop.
På dette grundlag kan den nødvendige stikprøvestørrelse til opfyldelse af standardkriterierne for bioækvivalens være så stor som 232 forsøgspersoner for at opnå en styrke på mindst 80 %. 
Considering this, the sample size that may be required to meet the standard bio-equivalence criteria would be as high as 232 subjects to obtain power of at least 80%.
• udvalget gennemgik alle de af ansøgeren forelagte data til dokumentation af bioækvivalensen mellem didanosin og relaterede navne og referenceproduktet. 
• The Committee reviewed all the data submitted by the applicant in order to support the bioequivalence between Didanosine and associated names and the reference product.
Da produktet skal administreres mindst to timer før eller efter et måltid, er det usandsynligt, at det indtagne produkt vil blive udsat for in vivobetingelser, der svarer til betingelserne i postprandial tilstand. 
Since the product is to be administrated at least 2 hours before or after food intake, it is unlikely that the product ingested will be exposed to in vivo conditions, prevailing under fed state.
Ansøgeren hævdede, at forskellene i plasmakoncentrationerne af didanosin ikke har klinisk relevans som sådan, da de ikke nødvendigvis medfører ændringer i de intracellulære koncentrationer af trifosfat. 
The applicant claimed that differences in plasma concentrations of didanosine are not of clinical relevance as such since it may not result in changes in the intracellular triphosphate concentrations.
Resultaterne var tilfredsstillende hvad angår absorptionsgraden (dvs. AUC). 
The results were satisfactory in terms of extent of absorption (i.e. AUC).
Ansøgningen for didanosin og relaterede navne blev vurderet i overensstemmelse med artikel 10, stk. 3 i direktiv 2001/83/EF i alle de berørte medlemsstater. 
The application for Didanosine and associated names was considered under Article 10.3 of Directive 2001/83/EC in all Concerned Members States (CMSs).
Den iagttagne virkning af fødeindtagelse er imidlertid lavere, og det er udvalgets opfattelse, at den ikke er klinisk relevant i betragtning af virkningsmekanismen og navnlig af, at didanosin og relaterede navne skal administreres på tom mave, 
However, the observed effect of food is lower and the Committee is of the opinion that this is not clinically relevant based on considerations relating to the mechanism of action and, in particular, that Didanosine and associated names is to be administrated on an empty stomach.
1 Retningslinjer for undersøgelse af biotilgængelighed og bioækvivalens (EMA/CPMP/EWP/QWP/1401/98) 2 Retningslinjer for farmakokinetisk og klinisk vurdering af lægemiddelformer med modificeret udløsning 
1 Note for Guidance on the investigation of bioavailability and bioequivalence (EMA/CPMP/EWP/QWP/1401/98) 2 Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms
Den decentrale procedure blev afsluttet på dag 210, hvor konklusionerne i referencemedlemsstatens vurderingsrapport fik tilslutning fra størstedelen af de berørte medlemsstater bortset fra Frankrig og Nederlandene, som rejste betænkelighed ved en potentiel alvorlig risiko for den offentlige sundhed. 
The decentralised procedure was closed on day 210, with most of the CMSs agreeing with the conclusions of the reference Member State (RMS)'s assessment report except France and the Netherlands which raised a potential serious risk to public health (PSRPH).
Det bemærkes, at bioækvivalens ved fastende betingelser anses for at have størst betydning, da produktet er bestemt til indtagelse på tom mave. 
Of note, bioequivalence in fasted state is considered to be the most important as this product is intended to be taken on an empty stomach.
Denne iagttagelse er på linje med de fremlagte resultater i den aktuelle ansøgning, hvor AUC og Cmax af testproduktet nedsættes væsentligt under postprandiale betingelser. 
This observation is in line with the results presented in the current application where AUC and Cmax of the test product significantly decrease under fed conditions.
anbefalede CHMP udstedelse af markedsføringstilladelserne, for hvilke produktresuméet, etiketteringen og indlægssedlen er uændrede svarende til endelige version, der er fastlagt ved behandlingen i koordinationsgruppen som anført i bilag III for didanosin og relaterede navne (se bilag I). 
the CHMP has recommended the granting of the marketing authorisations for which the summary of product characteristics, labelling and package leaflet remain as per the final versions achieved during the Coordination group procedure as mentioned in Annex III for Didanosine and associated names (see Annex I).
For referenceproduktet medfører administration sammen med et fedtrigt måltid en væsentlig nedsættelse af AUC (19 %) og af Cmax (46 %) for didanosin. 
The administration of the reference product with a high fat meal significantly decreases the AUC (19%) and Cmax (46%) of didanosine.
Didanosin og relaterede navne er i kombination med andre antiretrovirale lægemidler indiceret til behandling af hiv-1-smittede patienter. 
Didanosine and associated names is indicated in combination with other antiretroviral drugs for the treatment of HIV-1 infected patients.
Begge undersøgelser blev udført i et åbent, randomiseret enkeltdosis-overkrydsningsdesign med to behandlinger, to sekvenser og to perioder. 
Both studies were carried out using open label, randomised, two treatment, two sequence, two period, single dose cross-over design.
8 Schrader S et al. Comparison of HIV RNA suppression produced by triple regimens containing either didanosin enteric-coated or didanosin tablet formulations each administered once daily. 
Comparison of HIV RNA suppression produced by triple regimens containing either didanosine enteric-coated or didanosine tablet formulations each administered once daily.
De indledende kliniske undersøgelser til påvisning af virkningen af didanosin til behandling af hiv-infektion blev udført med bufrede tabletter3,4,5,6,7,8. 
didanosine in treatment of HIV infecting were conducted using buffered tablets3,4,5,6,7,8.
Ansøgeren fremførte, at det betydelige fald, der under postprandiale betingelser iagttages i Cmax af testproduktet (90 % SI uden for standard område), kan tilskrives interindividuel variabilitet af Cmax, som var 36 % i den postprandiale undersøgelse. 
The Applicant claimed that the significant decrease observed under fed conditions for Cmax for the test product (90% CI outside the standard range) may be attributed to high inter-individual variability with respect to Cmax which was 36% in the study conducted under fed conditions.
Bioækvivalensundersøgelserne bekræftede, at der ikke forekom dose-dumping med didanosin og relaterede navne. 
The bioequivalence studies confirmed that dose dumping did not occur with Didanosine and associated names.
Didanosin er bestemt til administration på tom mave som angivet i det ansøgte produktresumé: “Absorptionen af didanosin er nedsat i tilstedeværelse af føde, hvorfor didanosin enterokapsler skal administreres på tom mave (mindst to timer før eller to timer efter et måltid)”. 
Didanosine is intended to be administrated on en empty stomach as stated in the proposed Summary of Product Characteristics (SmPC): “Didanosine absorption is reduced in the presence of food, and hence Didanosine gastro-resistant capsules should be administrated on an empty stomach (at least 2 hours before or 2 hours after a meal)”.
Dette tilskrives den langsommere absorptionshastighed for den enterocoatede formulering, hvilket afspejler sig i Tmax, som er ca. 2 timer for enteroformuleringen mod 0,67 timer for den bufrede tablet. 
This is attributed to the delay in absorption rate of enteric coated formulation which is reflected in the Tmax which is about 2 hours for the enteric coated formulation compared to 0.67 hours for the buffered tablet.
• Den iagttagne effekt af fødeindtagelse for test- og referenceproduktet I henhold til de gældende anbefalinger for formuleringer med modificeret udløsning1,2 kræves der bioækvivalensundersøgelser ved fastende og postprandiale betingelser. 
• Observed food effect for test and reference products As per the current recommendations for modified release formulations1,2, bioequivalence studies in fasted and fed conditions are required.
De forelagte data fra giver ikke evidens for, at der optræder in vivo-dose-dumping fra formuleringen under postprandiale betingelser. 
The presented data does not give evidence of in vivo dose-dumping from the formulation under fed conditions.
13 Stevens RC et al. Effect of food and pharmacokinetic variability on didanosin systemic exposure in HIV-infected children. 
13 Stevens RC et al. Effect of food and pharmacokinetic variability on didanosine systemic exposure in HIV-infected children.
Didanosin (2', 3'-dideoxyinosin) er en hæmmer af in vitro-replikationen af humant immundefektvirus (hiv) i dyrkede humane celler og cellelinjer. 
Didanosine (2', 3'-dideoxyinosine) is an inhibitor of the in vitro replication of human immunodeficiency virus (HIV) in cultured human cells and cell lines.
Under den decentrale procedure anførte Frankrig og Nederlandene, at der ikke var påvist bioækvivalens under postprandiale betingelser, da Cmax var uden for godkendelsesgrænserne på 80-125 %1. 
During the decentralised procedure France and the Netherlands expressed the opinion that bioequivalence had not been demonstrated in the fed conditions as Cmax was outside the 80-125% acceptability limits1.
Didanosin skal først intracellulært omdannes til sin aktive metabolit, ddATP (der er ansvarlig for den antivirale aktivitet), som har en væsentligt længere intracellulær halveringstid (ca. 43 timer) end plasmahalveringstiden for didanosin. 
Didanosine has to be first converted intracellularly to its active metabolite ddATP (responsible for antiviral activity) which has a significantly longer intracellular half-life (about 43 hours) as compared with plasma half-life of didanosine.
Hovedformålet med den postprandiale bioækvivalensundersøgelse er at udelukke fødemiddeleffekt såsom “dose-dumping” (hurtig udløsning) (navnlig for enteroformuleringer) og manglende beskyttelse mod syremedieret nedbrydning i ventriklen. 
The main purpose of conducting bioequivalence fed study is to exclude food related effects, such as dose-dumping (in particular for gastro-resistant formulations) or failure of protection from acid mediated degradation in the stomach.
Det forhold, at begge formuleringer er blevet anvendt til samme indikationer og i samme doser, anses derfor for at tyde på, at AUC er mere relevant til sikring af virkningen af didanosin ved antiviral behandling, og at ændringerne i Cmax næppe vil forringe den antivirale virkning. 
Therefore, it is considered that the fact that both formulations have been used for the same indications and at similar doses suggests that AUC is more relevant for ensuring efficacy of didanosine in antiviral therapy, and the changes in Cmax are unlikely to compromise antiviral efficacy.
Didanosin og relaterede navne (enterokapsler, 400 mg) blev sammenlignet med referenceproduktet Videx EC (enterokapsler, 400 mg) hos 60 voksne forsøgspersoner under fastende betingelser. 
Didanosine and associated names (Gastro-resistant capsules 400 mg) was compared to the reference product Videx EC (Gastro-resistant capsules 400 mg) in 60 healthy adults under fasting conditions.
4 Damle BD et al. Bioequivalence of two formulations of didanosin, encapsulated enteric-coated beads and buffered tablet, in healthy volunteers and HIV-infected subjects. 
Damle BD et al. Bioequivalence of two formulations of didanosine, encapsulated enteric-coated beads and buffered tablet, in healthy volunteers and HIV-infected subjects.
De indsigende medlemsstater fandt desuden, at ansøgerens argumenter ikke tog tilstrækkeligt hensyn til konsekvenserne af den iagttagne forskel mellem testproduktet og referenceproduktet i farmakokinetikken af didanosin under postprandiale betingelser. 
In addition, the objecting Members States considered that the arguments provided by the applicant did not sufficiently address the consequences of the difference observed in didanosine pharmacokinetics in the fed state between test and reference products.
De farmakokinetiske undersøgelser, der er udført med formuleringer af didanosin, viser, at administration af produktet sammen med et måltid eller umiddelbart efter et måltid medfører nedsat in vivo-biotilgængelighed af lægemidlet. 
Pharmacokinetics studies conducted on Didanosine formulations reveal that administration of the product with food or immediately after food results in decreased in vivo availability of the drug.
De farmakokinetiske data viser, at den plasmakoncentration (C max), der opnås med didanosin formuleret som enterokapsler, er ca. 40 % lavere end med den bufrede tabletformulering. 
The pharmacokinetics data reveals that the plasma concentration (Cmax) obtained from enteric-coated capsule formulation of didanosine is about 40% lower as compared to the buffered tablet formulation.
Vurdering Til påvisning af sikkerheden og virkningen af didanosin og relaterede navne i kombination med andre antiretrovirale lægemidler til behandling af hiv-1-smittede patienter var ansøgningsdossieret baseret på to enkeltdosis-bioækvivalensundersøgelser, den ene under fastende betingelser, den anden under postprandiale betingelser. 
In order to demonstrate the safety and efficacy of Didanosine and associated names in combination with other antiretroviral drugs in the treatment of HIV-1 infected patients, the application dossier was based on two single dose bioequivalence studies, one under fasting state and one under fed state.
ddATP hæmmer desuden hivrevers transkriptase ved at konkurrere med deoxyadenosintrifosfat (dATP) om binding til enzymets aktive sæde, hvorved det hindrer den provirale DNA-syntese. 
In addition, ddATP inhibits HIV-reverse transcriptase by competing with deoxyadenosine-triphosphate (dATP) for binding to the enzyme's active site, preventing proviral DNA synthesis.
I den postprandiale undersøgelse var resultaterne tilfredsstillende hvad angår absorptionsgraden (dvs. AUC), idet 90 % SI var inden for standardområdet 80,00-125,00 %. 
In the fed study, the results were satisfactory in terms of extent of absorption (i.e. AUC) with 90% CI within standard range of 80.00 - 125.00%.
Når didanosin er trådt ind i cellen, omdannes det enzymatisk til dideoxyadenosintrifosfat (ddATP), som er den aktive metabolit. 
After didanosine enters the cell, it is enzymatically converted to dideoxyadenosine-triphosphate (ddATP), its active metabolite.
3 Damle BD et al. Pharmacokinetics and gamma scintigraphy evaluation of two enteric coated formulations of didanosin in healthy volunteers. 
Damle BD et al. Pharmacokinetics and gamma scintigraphy evaluation of two enteric coated formulations of didanosine in healthy volunteers.
I den virale nukleinsyrereplikation blokerer indbygningen af dette 2', 3'-dideoxynukleosid for kædeforlængelsen, hvorved det hæmmer den virale replikation. 
In viral nucleic acid replication, incorporation of this 2', 3'-dideoxynucleoside prevents chain extension, and thereby inhibits viral replication.
9 La Porte C et al. Pharmacokinetic interaction study of indinavir/ritonavir and the enteric-coated capsule formulation of didanosin in healthy volunteers. 
Chicago 2001 La Porte C et al. Pharmacokinetic interaction study of indinavir/ritonavir and the enteric-coated capsule formulation of didanosine in healthy volunteers.
Fødeindtagelse kan derfor anses for at have samme effekt på test- og referenceproduktet i form af reduktion af Cmax og AUC. 
Hence, both test and reference products can be considered as having similar food effect in terms of reduction in Cmax and AUC.
De primære farmakokinetiske parametre (Cmax og AUC) var tilfredsstillende i undersøgelsen ved fastende betingelser, idet 90 % sikkerhedsintervallet (SI) var inden for standardkriteriet på 80,00 
The primary pharmacokinetic parameters (Cmax and AUC) were satisfactory in the fasting study with the 90% confidence interval (CI) falling within the standard criteria of 80.00 - 125.00%.
Udvalget vedgik, at den maksimale plasmakoncentration (Cmax) var uden for acceptgrænserne 80-125 % ifølge det konventionelle kriterium for bioækvivalens. 
The Committee acknowledged that the conventional criterion for bioequivalence for maximum plasma concentration (Cmax) was outside the 80-125% acceptability limits.
Absorptionen af didanosin er således nedsat under postprandiale betingelser både for testproduktet og referenceproduktet, hvilket tyder på, at de to produkter påvirkes på samme måde af fødeindtagelse hvad angår reduktion af Cmax og AUC, uden at der er tegn på dose-dumping. 
Therefore, for both the test and the reference product in the fed state the absorption of didanosine decreases which indicate that both products possess similar food effect in terms of reduction in Cmax and AUC with no evidence of dose-dumping.
• udvalget bemærkede, at fødeindtagelse nedsatte plasmakoncentrationerne for begge formuleringer i den postprandiale undersøgelse. 
• The Committee noted that in the fed study, both formulations were subject to a food effect reducing plasma concentrations.
I den aktuelle ansøgning var AUC både under fastende og postprandiale betingelser inden for acceptkriteriet på 80-125 %. 
In the current application, the AUC under both fasted and fed conditions was within the acceptance criteria of 80
2006; 7: 155-162 11 Hernandez-novoa B et al. Effect of food on the antiviral activity of didanosin enteric-coated capsules: A pilot comparative study. 
Hernandez-novoa B et al. Effect of food on the antiviral activity of didanosine enteric-coated capsules: A pilot comparative study.
Lægemidlet er ikke længere autoriseret til salg©EMEA 2007 
Medicinal product no longer authorise©EMEA 2007
Europa-Kommissionen udstedte en markedsføringstilladelse for Velosulin med gyldighed i hele Den Europæiske Union til Novo Nordisk A/S den 7. oktober 2002. 
The European Commission granted a marketing authorisation valid throughout the EU for Velosulin to Novo Nordisk A/S on 7 October 2002.
Det forklarer, hvordan Udvalget for Humanmedicinske Lægemidler (CHMP) vurderede de gennemførte undersøgelser og nåede frem til sine anbefalinger om, hvordan lægemidlet skal 
It explains how the Committee for Medicinal products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
Velosulin var effektivt til behandling af såvel type 1- som type 2-diabetes. 
Velosulin was effective for both type 1 and type 2 diabetes.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved Velosulin er større end risiciene ved behandling af diabetes. 
The Committee for Medicinal products for Human Use (CHMP) decided that Velosulin's benefits are greater than its risks for the treatment of diabetes.
Hvilke risici er der forbundet med Velosulin? 
What is the risk associated with Velosulin?
Diabetes er en sygdom, hvor kroppen ikke producerer tilstrækkeligt insulin til at kontrollere blodsukkeret. 
Diabetes is a disease in which the body does not produce enough insulin to control the blood glucose.
Patientens blodsukker skal kontrolleres regelmæssigt for at fastsætte den effektive minimumsdosis. 
The patient's blood glucose (sugar) should be tested regularly to find the lowest effective dose.
Ved at holde bloksukkeret under kontrol mindskes sukkersygesymptomerne og -komplikationerne. 
By controlling the blood glucose, the symptoms and complications of diabetes are reduced.
Velosulin bør ikke anvendes hos personer, som kan være overfølsomme (allergiske) over for insulin human (rDNA) eller et af de øvrige stoffer. 
Velosulin should not be used in people who may be hypersensitive (allergic) to insulin human (rDNA) or to any of the other ingredients.
Erstatningsinsulinen fungerer på samme måde som naturligt produceret insulin og hjælper glukosen til at trænge ind i cellerne fra blodet. 
The replacement insulin acts in same way as naturally produced insulin and helps glucose to enter cells from the blood.
De undersøgelser, der understøtter brugen af Velosulin er de samme, som er blevet anvendt til at understøtte brugen af Actrapid, et andet insulinpræparat, der er godkendt i EU. 
The studies used to support Velosulin are those that have been used to support Actrapid, another insulin approved in the European Union (EU).
Velosulin medførte et fald i HbA1c-niveauet, hvilket tyder på, at blodsukkeret var blevet holdt under kontrol på et niveau, der svarede til det, der var observeret for andet humant insulin. 
Velosulin led to a decrease in the level of HbA1c, indicating that blood glucose levels had been controlled to a similar level to that seen with the other human insulin.
Velosulin indgives ved konstant subkutant infusion (under huden) ved hjælp af en insulininfusionspumpe. 
Velosulin is intended for continuous subcutaneous infusion (under the skin) using an insulin infusion pump.
I undersøgelserne målte man blodsukkeret i fastende tilstand eller mængden af et stof (glykosyleret hæmoglobin, HbA1c), der viser, hvor godt blodsukkeret reguleres. 
The studies measured the level of fasting blood sugar or a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.
Velosulin indeholder det aktive stof insulin human (rDNA). 
It contains the active substance insulin human (rDNA).