FrancophonIA/ELRC3.0 huggingface dataset:
English: A single dose study with galantamine 24 mg was not considered ethically acceptable as such a dose is not given as a first dose to patients.
Danish: En enkeltdosisundersøgelse med galantamin 24 mg blev ikke anset for etisk acceptabel, eftersom en sådan dosis ikke gives til patienterne som startdosis.
English: It was clear, that the way for computing Cmin as Cminss was preferred initially, and descriptive statistics for this parameter were submitted in the final study report.
Danish: Det stod klart, at måden at beregne Cmin som Cminss på oprindeligt blev foretrukket, og der blev indsendt beskrivende statistikker for dette parameter i den endelige undersøgelsesrapport.
English: Czech Republic
Danish: Den Tjekkiske republik
English: The Applicant also argued that %PTF is in fact a better parameter for the assessment of prolonged release products.
Danish: Ansøgeren fremførte ligeledes, at %PTF faktisk er et bedre parameter for vurderingen af depotlægemidler.
English: It was noted that while Cmin and Ctrough should be the same for immediate release products, they usually differ for prolonged release products.
Danish: Det blev bemærket, at mens Cmin og Ctrough burde være det samme for lægemidler med umiddelbar frigivelse, er de som regel forskellige for depotlægemidler.
English: The three single dose studies were carried out using the 8 and 16mg strengths:
Danish: De tre enkeltdosisundersøgelser blev foretaget ved hjælp af 8 mg- og 16 mg-styrkerne:
English: The intra-subject coefficient of variation (IS-CV) of Cminss was found to be markedly higher in comparison to Cmaxss (37.2 % vs. 11.1% for the 24mg strength).
Danish: Cminss' variationskoefficient for de enkelte deltagere i undersøgelsen (IS-CV) viste sig at være markant højere sammenlignet med Cmaxss (37,2 % sammenlignet med 11,1 % for 24 mg-styrken).
English: Furthermore as mentioned previously the Cpd and Ctrough definitions are indeed considered post-hoc, introducing an unacceptable level of bias.
Danish: Som nævnt før tages Cpd- og Ctrough-definitionerne i betragtning efterfølgende, hvilket giver et uacceptabelt skævvridningsniveau.
English: A single dose study with 24 mg was considered to be acceptable due to the poor tolerability of galantamine in patients and in healthy volunteers, provided that the following multiple dose study was performed, which included the 24 mg dose:
Danish: En enkeltdosisundersøgelse med 24 mg blev anset for acceptabel som følge af galantamins ringe tolerabilitet hos patienterne og hos sunde frivillige, under forudsætning af at der blev foretaget følgende flerdosisundersøgelse, som omfattede 24 mgdosen:
English: The CHMP were of the view that the requirements of this guideline are clear and they are based on the principle that using a derived parameter (such as %PTF) for the pharmacokinetic evaluation decreases the sensitivity to detect a possible difference between products
Danish: CHMP var af den opfattelse, at kravene i disse retningslinjer er klare, og de er baseret på princippet om, at brugen af et afledt parameter (såsom %PTF) til den farmakokinetiske vurdering mindsker muligheden for at opdage en eventuel forskel mellem lægemidlerne.
English: 1) Cminss defined as the lowest concentration on a concentration-time curve at steady-state within one dosing interval including the pre-dose concentration value.
Danish: 1) Cminss defineret som den laveste koncentration på en koncentration/tid-kurve ved steady state inden for et dosisinterval, der omfatter førdosiskoncentrationsværdien.
English: Additionally the Applicant also presented as supportive data the peak-trough-fluctuation (%PTF) values for all three strengths and an analysis using repeated measurements of Cmin pd at days 10, 11 and 12 (i.e. at the 24 mg dose) of the multiple dose study.
Danish: Som underbyggende data fremlagde ansøgeren desuden PTF-værdierne (%PTF) for alle tre styrker og en analyse, hvor der var anvendt gentagne målinger af Cmin pd på dag 10, 11 og 12 (dvs. for 24 mgdosen) i flerdosisundersøgelsen.
English: The CHMP was therefore of the view that the risk benefit ratio of Galantamine STADA is negative and that a marketing authorization should not be granted.
Danish: CHMP var således af den opfattelse, at risk/benefit-forholdet for Galantamin STADA er negativt, og at der derfor ikke bør udstedes markedsføringstilladelse.
English: If the Cmin values of the test product tend to decrease more than in a reference product, one could also expect lower clinical efficacy of the test product.
Danish: Hvis testlægemidlets Cmin-værdier har en tendens til at falde mere end i et referencelægemiddel, kan man ligeledes forvente, at testlægemidlet har en ringere klinisk virkning.
English: 2) Cminss defined as the concentration immediately before the 4th dose (Cpd)
Danish: 2) Cminss defineret som koncentrationen umiddelbart før den fjerde dosis (Cpd).
English: This is a product, which is intended to present prolonged release characteristics and therefore the maintenance of sufficient plasma levels is among the main parameters connected to the claimed pharmaceutical form.
Danish: Det er et lægemiddel, som skal have depotkarakteristika, og derfor er fastholdelsen af tilstrækkelige plasmaniveauer et af de vigtigste parametre i forbindelse med den lægemiddelform, der er genstand for ansøgningen.
English: The CHMP was of the view that Cmin is considered to be an important rate parameter especially in multiple dose bioequivalence studies, and that demonstration of bioequivalence is of paramount importance.
Danish: CHMP var af den opfattelse, at Cmin anses for at være et vigtigt vurderingsparameter, navnlig i flerdosisundersøgelserne af bioækvivalens, og at påvisningen af bioækvivalens er af yderste vigtighed.
English: As apparent from the protocol, Cmin (defined as minimum drug concentration in the dosing interval) was pre-specified as secondary parameter (descriptive statistics) and descriptive Cmin data had already been reported in the initial submission.
Danish: Som det fremgik af protokollen, var Cmin (defineret som den laveste lægemiddelkoncentration i dosisintervallet) præspecificeret som sekundært parameter (beskrivende statistik), og beskrivende Cmin-data var allerede blevet indberettet i forbindelse med den første indsendelse.
English: In the study protocol of the multiple dose study, AUCT and Cmaxss after the 24 mg dose were proposed as primary parameters (for which bioequivalence was shown in the conventional bioequivalence range), while Cminss was not defined as primary pharmacokinetic parameter.
Danish: I undersøgelsesprotokollen for flerdosisundersøgelsen blev AUCT og Cmaxss efter 24 mg-dosen foreslået som de primære parametre (for hvilke bioækvivalensen lå inden for det konventionelle bioækvivalensinterval), mens Cminss ikke var defineret som et primært farmakokinetisk parameter.
English: The reference product is Reminyl 8mg/16mg and 24mg in the form of prolonged release capsules.
Danish: Referencelægemidlet er Reminyl 8 mg, 16 mg og 24 mg i form af depotkapsler.
English: A single dose study with the 16 mg dose after a high fat meal Single dose studies with the 8 mg and 16 mg formulations demonstrated bioequivalence with the reference product Reminyl (once daily), not only in the conventional bioequivalence range of 80-125%, but in an even tighter range of 90-111% for both AUCt and Cmax.
Danish: Enkeltdosisundersøgelserne med 8 mg- og 16 mg-formuleringerne viste bioækvivalens med referencelægemidlet Reminyl (taget én gang om dagen), ikke kun inden for det konventionelle bioækvivalensinterval på 80-125 %, men også inden for et endnu snævrere interval på 90-111 % for både AUCt og Cmax.
English: The Applicant was requested by the CHMP to provide justification for the choice of the method for Cmin calculation in the steady state study and also to discuss which definition of Cmin would best reflect the prolonged release characteristics of the product and allow detection of possible differences between test and reference product.
Danish: CHMP bad ansøgeren om at give en begrundelse for valget af metode for Cmin-beregningen i steady state-undersøgelsen og ligeledes om at gøre rede for, hvilken definition af Cmin der bedst ville afspejle lægemidlets depotkarakteristika og gøre det muligt at opdage eventuelle forskelle mellem testlægemiddel og referencelægemiddel.
English: The presented results of the single multiple dose steady state study demonstrated that Cmin values after the test product are likely to be substantially lower in comparison to the reference product.
Danish: De fremlagte resultater af den enkelte steady state-flerdosisundersøgelse viste, at Cmin-værdierne efter testlægemidlet sandsynligvis er væsentligt lavere sammenlignet med referencelægemidlet.
English: The CHMP agreed that although there is no explicit recommendation for computing of Cmin for prolonged release products at the present time, recommendations connected to immediate release products cannot be extrapolated to prolonged release products, which differ from immediate release products with respect to the shape of the pharmacokinetic profile.
Danish: CHMP var enig i, at selv om der på nuværende tidspunkt ikke er nogen udtrykkelige anbefalinger for beregningen af Cmin for depotlægemidler, kan anbefalingerne i forbindelse med lægemidler med umiddelbar frigivelse ikke ekstrapoleres til depotlægemidler, som er forskellige fra lægemidler med umiddelbar frigivelse, når det gælder den farmakokinetiske profil.
English: 3) Cminss defined as the concentration 24 h after the 4th dose immediately before the next dose would be administered (Ctrough)
Danish: 3) Cminss defineret som koncentrationen 24 timer efter den fjerde dosis og umiddelbart inden næste dosis skal indgives (Ctrough).
English: Taking into account all the arguments presented, the CHMP agreed that the originally prespecified Cminss values most adequately described the release characteristics of the product in this situation.
Danish: CHMP tog alle de fremførte argumenter i betragtning og var enig i, at de oprindeligt præspecificerede Cminss-værdier var de mest velegnede til at beskrive depotkarakteristikaene for lægemidlet i denne situation.
English: Three single dose studies and one steady state study have been conducted to establish bioequivalence of the prolonged release tablets Galantamine STADA in comparison to the reference product Reminyl prolonged release capsules.
Danish: Der er blevet foretaget tre enkeltdosisundersøgelser og en steady state-undersøgelse for at fastlægge bioækvivalensen for Galantamin STADA depottabletter sammenlignet med referencelægemidlet Reminyl depotkapsler.
English: The CHMP concluded that bioequivalence had not been shown and that the pharmacokinetic characteristics suggest inferior performance of Galantamine STADA prolonged release capsules in comparison with the reference product.
Danish: CHMP konkluderede, at der ikke var påvist bioækvivalens, og at de farmakokinetiske egenskaber tyder på, at Galantamin STADA depotkapsler er mindre effektive end referenceproduktet.
English: Furthermore the pooling of the pre-dose concentrations (Cmin) in the steady state study at day 10/11/12 as a proof of bioequivalence instead of standard non-pooled data (replicate design), was not considered to be acceptable by the CHMP.
Danish: Desuden var CHMP af den opfattelse, at poolingen af førdosiskoncentrationerne (Cmin) i steady stateundersøgelsen på dag 10, 11 og 12 ikke var acceptabel som et bevis for bioækvivalens i stedet for ikke-poolede data (undersøgelse med gentagelser).
English: IS-CV of the single dose studies had been taken into account for the sample size calculation of the multiple dose study and that the study was not powered for the higher IS-CV of Cminss.
Danish: Ansøgeren forklarede, at IS-CV i enkeltdosisundersøgelserne var blevet taget i betragtning ved prøvestørrelsesberegningen for flerdosisundersøgelsen, og at undersøgelsen ikke tog sigte på en højere IS-CV for Cminss.
English: Cminss and peak-trough fluctuation (PTF) were considered as secondary parameters as well as all pharmacokinetic parameters for the other two dosage strengths The multiple dose study was designed to mirror clinical conditions by up-titration of all three doses.
Danish: Cminss og PTF (peak-trough fluctuation) blev anset for at være sekundære parametre ligesom alle farmakokinetiske parametre for de to andre doseringsstyrker.
English: A single dose study with the 8 mg dose under fasting conditions
Danish: En enkeltdosisundersøgelse med 8 mg-dosen i fastende tilstand
English: Strength Pharmaceutical Form Route of administration
Danish: Lægemiddelform Indgivelsesvej
English: However the CHMP noted that since the study did not have a replicate design, the IS-CV may in fact also include differences between products and is not true intra-subject CV.
Danish: CHMP bemærkede dog, at eftersom det ikke var en undersøgelse med gentagelser, kan IS-CV reelt også omfatte forskelle mellem lægemidlerne, hvilket indebærer, at det ikke er en egentlig variationskoefficient for de enkelte deltagere i undersøgelsen.
English: A single dose study with the 16 mg dose under fasting conditions
Danish: En enkeltdosisundersøgelse med 16 mg-dosen i fastende tilstand
English: In addition the CHMP was also of the view that for cholinesterase inhibitors like galantamine, the relationship between administered dose and therapeutic effect is not entirely clear, and for this reason the results from the bioequivalence studies are considered to be of primary importance in this application.
Danish: Desuden var CHMP af den opfattelse, at når det gælder cholinesterasehæmmere som galantamin, er forholdet mellem den indgivne dosis og den terapeutiske effekt ikke fuldstændigt klart.
English: “Assessment of bioequivalence will be based on AUCτ, Cmax and Cmin applying similar statistical procedures as for the immediate release formulations.”
Danish: Release Oral and Transdermal Dosage Forms" (CPMP/EWP/280/96 corr), hvor der står, at følgende gælder for steady state-undersøgelsen: "Vurderingen af bioækvivalens vil være baseret på AUCτ, Cmax og Cmin, idet der anvendes de samme statistiske procedurer som for formuleringer med umiddelbar frigivelse."
English: However the CHMP highlighted Section 5 of the current CPMP Note for Guidance on Modified Release Oral and Transdermal Dosage Forms (CPMP/EWP/280/96 corr), which states that the following applies for the steady state study:
Danish: CHMP henviste dog til punkt 5 i CHMP's gældende "Note for Guidance on Modified
English: GALANTAX XL 8 mg prolonged-release tablets
Danish: GALANTAX XL 8 mg prolonged-release tablets 8 mg
English: GALANTAX XL 16 mg prolonged-release tablets
Danish: GALANTAX XL 16 mg prolonged-release tablets 16 mg
English: GALANTAX XL 24 mg prolonged-release tablets 24 mg
Danish: GALANTAX XL 24 mg prolonged-release tablets
English: Whereas
Danish: Styrke
English: Pharmaceutical Form
Danish: Lægemiddelform Indgivelsesvej
English: Invented name Strength
Danish: Særnavn
English: London, 24 January 2008 Doc.
Danish: London, den 24. januar 2008 Dok.
English: QUESTIONS AND ANSWERS ON THE WITHDRAWAL OF THE MARKETING APPLICATION for SINEREM
Danish: SPØRGSMÅL OG SVAR I FORBINDELSE MED TILBAGETRÆKNING AF ANSØGNINGEN OM MARKEDSFØRINGSTILLADELSE for SINEREM
English: The CHMP normally takes up to 210 days to evaluate a new application.
Danish: CHMP bruger normalt op til 210 dage på at evaluere en ny ansøgning.
English: The application was at day 175 when the company withdrew.
Danish: Ansøgningsproceduren var ved dag 175, da virksomheden trak sin ansøgning tilbage.
English: What is Sinerem?
Danish: Hvad er Sinerem?
English: What documentation did the company present to support its application to the CHMP?
Danish: Hvilken dokumentation har virksomheden fremlagt til støtte for sin ansøgning til CHMP?
English: The effects of Sinerem were first tested in experimental models before being studied in humans.
Danish: Virkningerne af Sinerem er først blevet undersøgt i forsøgsmodeller, inden de blev undersøgt hos mennesker.
English: If you are in a clinical trial or compassionate use programme and need more information about your treatment, contact the doctor who is giving it to you.
Danish: Hvis du deltager i en klinisk undersøgelse eller i et program for anvendelse med særlig udleveringstilladelse og har behov for yderligere oplysninger om din behandling, kan du kontakte den læge, der giver behandlingen.
English: It was to be used as a ‘contrast agent' to help make internal body structure more visible on the scan.
Danish: Det skulle anvendes som et "kontraststof" for at hjælpe med at gøre den indre legemsstruktur mere synlig på scanningen.
English: How far into the evaluation was the application when it was withdrawn?
Danish: Hvor langt var man kommet med evalueringen, da ansøgningen blev trukket tilbage?
English: What was the recommendation of the CHMP at that time?
Danish: Hvad var CHMP's anbefaling på det pågældende tidspunkt?
English: It contains extremely small particles of iron oxide (nanoparticles).
Danish: Det indeholder meget små jernoxidpartikler (nanopartikler).
English: Following the CHMP's opinion, it usually takes around 2 months for the European Commission to grant a licence.
Danish: Efter at CHMP har afgivet sin udtalelse, er Europa-Kommissionen sædvanligvis ca. to måneder om at udstede tilladelsen.
English: What was Sinerem expected to be used for?
Danish: Hvad forventedes Sinerem anvendt til?
English: What were the main concerns of the CHMP?
Danish: Hvori bestod CHMP's største betænkeligheder?
English: There was one main study of the effectiveness of Sinerem, involving a total of 271 patients with pelvic cancers.
Danish: Der var én hovedundersøgelse af effekten af Sinerem med i alt 271 patienter med cancer i bækkenregionen.
English: Based on the review of the initial documentation, the CHMP prepares a list of questions at day 120, which is sent to the company.
Danish: På baggrund af gennemgangen af den oprindelige dokumentation udarbejder CHMP en liste med spørgsmål på dag 120, og denne liste fremsendes til den pågældende virksomhed.
English: This should help making a difference between normal lymph nodes that contain macrophages and therefore magnetic particles, and lymph nodes that are invaded with cancer cells and contain fewer macrophages and fewer magnetic particles.
Danish: Det skulle gøre det nemmere at skelne imellem normale lymfeknuder, som indeholder makrofager og derfor magnetiske partikler, og lymfeknuder, som er invaderet af cancerceller og indeholder færre makrofager og færre magnetiske partikler.
English: Once the company has supplied responses to the questions, the CHMP reviews them and may, before giving an opinion, ask any remaining questions at day 180.
Danish: Når virksomheden har afgivet sine svar på spørgsmålene, gennemgår CHMP disse og stiller eventuelt yderligere spørgsmål på dag 180, inden det afgiver sin udtalelse.
English: When exposed to the action of an external magnet as during an MRI scan, the particles become magnetic, and they can be seen more easily on the scan image.
Danish: Når de udsættes for virkningen fra eksterne magneter under en MR-scanning, bliver partiklerne magnetiske og kan nemmere ses på scanningsbilledet.
English: These are part of the lymphatic system, a network of structures in the body involved in body defence (immune system).
Danish: De indgår i det lymfatiske system, et netværk af strukturer i kroppen, som har med kroppens immunforsvar at gøre.
English: The patients underwent two MRI scans to detect any cancer cells in their lymph nodes, one with Sinerem and one without.
Danish: Patienterne gennemgik to MR-scanninger for at påvise eventuelle cancerceller i deres lymfeknuder, en med Sinerem og en uden.
English: The patients then had an operation to remove the lymph nodes, and the results of the scans were compared by three different specialist readers to the results obtained when looking at the lymph nodes under a microscope to see if they contained any cancer cells.
Danish: Patienterne fik derefter fjernet lymfeknuderne ved en operation, og resultaterne af scanningerne blev af tre forskellige specialister sammenlignet med de resultater, som var fremkommet ved at betragte lymfeknuderne under et mikroskop for at se, om de indeholdt cancerceller.
English: Active substance: Superparamagnetic iron oxide nanoparticles stabilised with dextran and sodium citrate
Danish: Superparamagnetisk jernoxid nanopartikler stabiliseret med dextran og natriumcitrat
English: When a cancer is in the process of spreading, the cancer cells travel within the lymphatic system, and can be detected in the lymph nodes.
Danish: Når en cancer er i færd med at sprede sig, bevæger cancercellerne sig inde i det lymfatiske system og kan registreres i lymfeknuderne.
English: How is Sinerem expected to work?
Danish: Hvordan forventedes Sinerem at virke?
English: Sinerem was to be used to see if the cancer was spreading, by helping visualise the patients' lymph nodes.
Danish: Sinerem skulle anvendes til at vise, om canceren spredte sig, ved at hjælpe med at visualisere patientens lymfeknuder.
English: The active substance in Sinerem is iron oxide in the form of nanoparticles in a clear, colloidal (jellylike) solution of dextran, a type of sugar.
Danish: Det aktive stof i Sinerem er jernoxid i form af nanopartikler i en klar kolloid (gelelignende) opløsning af dextran, som er en sukkertype.
English: On 13 December 2007, Guerbet officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Sinerem, intended for diagnostic use for the characterisation of lymph nodes visualised by MRI (magnetic resonance imaging) in the evaluation of primary tumour spread in pelvic cancers.
Danish: Den 13. december 2007 meddelte Guerbet officielt Udvalget for Humanmedicinske Lægemidler (CHMP), at man ønsker at trække sin ansøgning tilbage om markedsføringstilladelse for Sinerem til diagnostisk brug ved karakterisering af lymfeknuder visualiseret ved MR-scanning (magnetisk resonansscanning) under evaluering af primær tumorspredning ved cancer i bækkenregionen.
English: The main concern of the CHMP was that the effectiveness of Sinerem in enhancing the images seen in the MRI scan had not been shown.
Danish: CHMP's største betænkeligheder var, at Sinerems effekt med hensyn til at forstærke billederne i MRscanningen ikke var blevet påvist.
English: What are the consequences of the withdrawal for patients undergoing clinical trials / compassionate use programmes with Sinerem?
Danish: Hvilke konsekvenser har tilbagetrækningen for patienter, der deltager i kliniske undersøgelser med Sinerem eller i programmer for anvendelse med særlig udleveringstilladelse?
English: Sinerem is a powder to be made up into a solution for infusion (drip into a vein).
Danish: Sinerem er et pulver til fremstilling af en infusionsopløsning (intravenøst drop).
English: Pelvic cancers are cancers affecting organs in the lower abdomen, such as the prostate gland, the bladder, the womb or the cervix.
Danish: Cancer i bækkenregionen omfatter cancer som påvirker organerne i den nederste del af maven som prostata, blæren, underlivet eller livmoderhalsen.
English: Therefore, at the time of the withdrawal, the CHMP's view was that the benefits of Sinerem as a diagnostic agent in the characterisation of lymph nodes in patients with pelvic cancer had not been sufficiently demonstrated and any benefits did not outweigh the identified risks.
Danish: På tidspunktet for tilbagetrækning var det CHMP's opfattelse, at fordelene ved Sinerem som diagnostisk middel ved karakterisering af lymfeknuder hos patienter med cancer i bækkenregionen ikke var tilstrækkelig påvist, og at eventuelle fordele ikke opvejede de identificerede risici.