natgillin/translations-raw huggingface dataset:
Af de 704 patienter, som blev vurderet i MM- 009 og MM- 010 studierne, var 44, 6% i alderen 65 år og derover.
Of the 704 patients evaluated in the MM-009 and MM-010 studies, 44.6% were aged 65 or over.
I begge studier tog patienterne i lenalidomid / dexamethason - (len/ dex) - gruppen 25 mg lenalidomid peroralt, én gang dagligt på dag 1 til 21 og en tilsvarende placebokapsel én gang dagligt på dag 22 til 28 i hver 28- dages cyklus.
In both studies, patients in the lenalidomide/dexamethasone (len/dex) group took 25 mg of lenalidomide orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle.
Patienter i placebo/ dexamethason - (placebo/ dex) - gruppen tog 1 placebokapsel på dag 1- 28 i hver 28- dages cyklus.
Patients in the placebo/dexamethasone (placebo/dex) group took 1 placebo capsule on Days 1 to 28 of each 28-day cycle.
Patienter i begge behandlingsgrupper tog 40 mg dexamethason peroralt én gang dagligt på dag 1 til 4, 9 til 12 og 17 til 20 i hver 28- dages cyklus i de første 4 cyklusser af behandlingen.
Patients in both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy.
Dosis af dexamethason blev reduceret til 40 mg peroralt, én gang dagligt på dag 1 til 4 i hver 28- dages cyklus efter de første 4 cyklusser af behandlingen.
The dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 of each 28-day cycle after the first 4 cycles of therapy.
I begge studier var dosisjusteringer baseret på kliniske fund og laboratoriefund tilladt.
In both studies, dose adjustments were allowed based on clinical and laboratory finding.
Det primære endpoint i begge studier var tid til progression (TTP, Time To Progression).
The primary efficacy endpoint in both studies was time to progression (TTP).
I alt 351 patienter blev evalueret i MM- 010 studiet; heraf 176 i lenalidomid/ dexamethason- gruppen og 175 i placebo/ dexamethason- gruppen.
In total, 353 patients were evaluated in the MM-009 study; 177 in the lenalidomide/dexamethasone group and 176 in the placebo/dexamethasone group and, in total, 351 patients were evaluated in the MM-010 study; 176 in the lenalidomide/dexamethasone group and 175 in the placebo/dexamethasone group.
I begge studier blev baseline- demografiske og sygdomsrelaterede karakteristika sammenlignet mellem lenalidomid/ dexamethason- og placebo/ dexamethason- grupperne.
In both studies, the baseline demographic and disease-related characteristics were comparable between the lenalidomide/dexamethasone and placebo/dexamethasone groups.
ECOG - (Eastern Cooperative Oncology Group) - performance- status var næsten ens for begge grupper, hvilket også gjaldt for antallet og typen af tidligere behandlinger.
The ECOG performance status was comparable between both groups, as was the number and type of prior therapies.
Forud planlagte interrim- analyser af begge studier viste, at lenalidomid/ dexamethason statistisk var væsentligt bedre (p < 0, 00001) end dexamethason alene til at nå det primære endpoint, TTP.
Pre-planned interim analyses of both studies showed that lenalidomide/dexamethasone was statistically significantly superior (p < 0.00001) to dexamethasone alone for the primary efficacy endpoint, TTP.
Frekvenserne for fuldstændig respons (CR, Complete Response) og samlet respons (OR, Overall
Complete response (CR) and overall response (OR) rates in the lenalidomide/dexamethasone arm were also significantly higher than the dexamethasone/placebo arm in both studies.
Resultaterne fra disse analyser førte derefter til en afblinding i begge studier for at gøre det muligt for patienter i placebo/ dexamethason- gruppen at modtage behandling med lenalidomid/ dexamethason- kombinationen.
Results of these analyses subsequently led to an unblinding in both studies, in order to allow patients in the placebo/dexamethasone group to receive treatment with the lenalidomide/dexamethasone combination.
Tabel 1 giver en oversigt over responsfrekvenser baseret på bedømmelse af bedste respons for MM- 009 - og MM- 010- studierne.
Table 1 summarises response rates based on the best response assessments for studies MM-009 and MM-010.
I en poolet opfølgningsanalyse af MM- 009 - og MM- 010- studierne (n = 704), var gennemsnitstiden for TTP 48, 3 uger (95% konfidensinterval:
In a pooled follow-up analysis of studies MM-009 and MM-010 (N = 704), the median TTP was 48.3 weeks (95% CI:
41, 1; 60, 1) hos de patienter, der fik behandling med lenalidomid/ dexamethason (n = 353), mens gennemsnitstiden for TTP var 20, 1 uger (95% konfidensinterval:
41.1, 60.1) in patients treated with lenalidomide/dexamethasone (n = 353) versus 20.1 weeks (95% CI:
19, 9; 20, 7) i placebo/ dexamethason- patientgruppen (n = 351).
19.9, 20.7) in patients treated with placebo/dexamethasone (n = 351).
Gennemsnitstiden for progressionsfri overlevelse (PFS, Progression Free Survival) var 47, 3 uger (95% konfideninterval:
The median time of progression free survival (PFS) was 47.3 weeks (95% CI:
36, 9; 58, 4) hos patienterne, der fik behandling med lenalidomid/ dexamethason, mens den var på 20, 1 uger (95% konfidensinterval:
36.9, 58.4) in patients treated with lenalidomide/dexamethasone versus 20.1 weeks (95% CI:
18, 1; 20, 3) i placebo/ dexamethason- patientgruppen.
18.1, 20.3) in patients treated with placebo/dexamethasone.
Behandlingens gennemsnitsvarighed var på 28, 1 uger (min:
The median duration of treatment was 28.1 weeks (min:
Frekvenserne for fuldstændig respons (CR, Complete Response), delvis respons (PR, Partial Response) og samlet respons (OR, Overall Response) i lenalidomid/ dexamethason- armen var væsentligt højere end i dexamethason/ placebo- armen i begge studier.
Complete response (CR), partial response (PR) and overall response (OR) rates in the lenalidomide/dexamethasone arm were significantly higher than in the dexamethasone/placebo arm in both studies.
Gennemsnitsvarigheden af opfølgningen var 98, 0 uger (min:
The overall survival (OS) in the pooled studies at one year after the start of treatment was 82% in patients treated with lenalidomide/dexamethasone versus 75% in patients treated with placebo/dexamethasone, with a median follow-up duration of 98.0 weeks (min:
Selvom 170 ud af 351 patienter, som blev randomiseret til placebo/ dexamethason, modtog behandling med lenalidomid/ dexamethason, efter at studierne var blevet afblindet, viste den poolede analyse af den samlede overlevelse (OS) en statistisk væsentlig overlevelsesfordel for lenalidomid/ dexamethason sammenlignet med placebo/ dexamethason (hazard ratio = 0, 75, 95% konfidensinterval = [0, 59; 0, 95], p = 0, 015).
Despite the fact that 170 out of the 351 patients randomised to placebo/dexamethasone received treatment with lenalidomide/dexamethasone after the studies were unblinded, the pooled analysis of OS demonstrated a statistically significant survival advantage for lenalidomide/dexamethasone relative to placebo/dexamethasone (hazard ratio = 0.75, 95% CI = [0.59, 0.95], p=0.015).
Tabel 1 giver en oversigt over de vigtigste effektresultater af de poolede opfølgningsanalyser for MM- 009 - og MM- 010- studierne.
Table 1 summarises key efficacy results of the pooled follow-up analyses of studies MM-009 and MM-010.
Tabel 1:
13 Table 1:
Oversigt over resultater for effektanalyser på tidspunktet for afblinding af studierne — Poolede MM- 009 og MM- 010 studier
Summary of Results of Efficacy Analyses as of Dates Studies Were Unblinded — Pooled Studies MM-009 and MM-010
Hazard ratio/ Odds ratioa, 95% konfideninterval, p- værdi
Hazard ratio/odds ratioa,
Gennemsnitlig Time To Progression [uger]
Median Time To Progression [weeks]
0, 35 [0, 29; 0, 43] p < 0, 001 b
0.35 [0.29, 0.43]
Overall Response [n,%]
Overall Response [n,%]
0, 18 [0, 13; 0, 25], p < 0, 001 c
0.18 [0.13, 0.25], p < 0.001 c
Complete Response [n,%]
Complete Response [n,%]
0, 12 [0, 05; 0, 26], p < 0, 001 c
0.12 [0.05,0.26], p < 0.001 c
Partial Response [n,%]
Partial Response [n,%]
161 (45, 6)
161 (45.6)
70 (19, 9)
70 (19.9)
0, 30 [0. 21; 0, 42], p < 0, 001 c
0.30 [0.21, 0.42], p < 0.001 c
Gennemsnitlig Progression Free Survival [uger]
Median Progression Free Survival [weeks]
47, 3
47.3
0, 38 [0, 32; 0, 46] p < 0, 001 b
0.38 [0.32, 0.46]
[36, 9; 58, 4]
[36.9, 58.4] [18.1, 20.3]
1- års Overall Survival- frekvens
1-year Overall Survival rate
0, 75 [0, 59, 0, 95] 0, 015 b
0.75 [0.59, 0.95] p = 0.015 b
Hazard ratio gælder for TTP, PFS og OS; odds ratio for responsfrekvenser.
Hazard ratio is for TTP, PFS and OS, odds ratio is for response rates.
En værdi under 1 i kombination med en p- værdi på under 0, 025 tyder på, at len/ dex er placebo/ dex overlegen b:
A value below 1 in combination with a P value below 0.025 indicates superiority of len/dex over placebo/dex b:
One- tailed log rank test c:
One- tailed log rank test c:
One tailed kontinuitetskorrigeret chi- square test
One tailed continuity-corrected chi-square test
Lenalidomid har et asymetrisk kulstofatom og kan derfor eksistere som de optisk aktive former S (-) and R( +).
Lenalidomide has an asymmetric carbon atom and can therefore ex ist as the optically active forms S(-) and R(+).
Lenalidomid er generelt mere opløselig i organiske opløsningsmidler, men udviser den største opløselighed i 0, 1N HCl- buffer.
Lenalidomide is generally more soluble in organic solvents but exhibits the greatest solubility in 0.1N HCl buffer.
Absorption Lenalidomid absorberes hurtigt hos raske frivillige efter peroral administration med maksimale plasmakoncentrationer mellem 0, 625 og 1, 5 timer efter dosisindtagelse.
Absorption Lenalidomide, in healthy volunteers, is rapidly absorbed following oral administration with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose.
Administration samtidig med mad ændrer ikke absorptionens omfang.
Co-administration with food does not alter the extent of absorption.
Den maksimale koncentration (Cmax) og arealet under koncentrationstidskurven (AUC) øges proportionalt med stigende dosis.
The maximum concentration (Cmax) and area-under-the- concentration time curve (AUC) increase proportionately with increases in dose.
Gentagne doseringer forårsager ingen udpræget akkumulering af lægemidlet.
Multiple dosing does not cause marked drug accumulation.
Den relative eksponering af lenalidomids S - og R- enantiomerer i plasma er ca. henholdsvis 56% og 44%.
In plasma, the relative exposures of the S- and R- enantiomers of lenalidomide are approximately 56% and 44%, respectively.
Fordeling (14C) - lenalidomids binding til plasmaproteiner in vitro var lav med gennemsnitlig plasmaproteinbinding på 22, 7% og 29, 2% hos henholdsvis patienter med myelomatose og raske forsøgspersoner.
Distribution In vitro (14C)-lenalidomide binding to plasma proteins was low with mean plasma protein binding at 22.7% and 29.2% in multiple myeloma patients and healthy volunteers, respectively.
Metabolisme og udskillelse In vitro- forsøg tyder på, at lenalidomid ikke har nogen hæmmende virkning på CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 og CYP3A.
Metabolism and excretion In vitro studies indicate that lenalidomide has no inhibitory effect on CYP1 A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A.
Størstedelen af lenalidomid udskilles uændret via nyrerne.
A majority of lenalidomide is eliminated unchanged through urinary excretion.
Hos patienter med normal nyrefunktion udgjorde den andel, som blev udskilt via nyrerne, 65- 85% af den samlede clearance.
The contribution of renal excretion to total clearance in subjects with normal renal function was 65-85%.
Det er observeret, at eliminations- halveringstiden øges med dosis fra cirka 3 timer ved 5 mg op til cirka 9 timer ved doser på 400 mg (den højere dosis menes at give et bedre estimat af t½).
The half-life of elimination has been observed to increase with dose, from approximately 3 hours at 5 mg up to approximately 9 hours at doses of 400 mg (the higher dose is believed to provide a better estimate of t½).
Steady- state- niveau nås på dag 4.
Steady-state levels are achieved by Day 4.
Farmakokinetiske analyser hos patienter med nedsat nyrefunktion antyder, at nedsættelsen af nyrefunktionen (< 50 ml/ min) falder proportionelt med den samlede lægemiddeleliminering, hvilket giver en stigning i AUC.
Pharmacokinetics analyses in patients with impaired renal function indicate that as renal function decreases (< 50 ml/min), the total drug clearance decreases proportionally resulting in an increase in AUC.
3, 5 timer hos forsøgspersoner med kreatinin- clearance > 50 ml/ min til mere end 9 timer hos forsøgspersoner med nedsat nyrefunktion < 50 ml/ min.
The half-life of lenalidomide increased from approximately 3.5 hours in subjects with creatinine clearance > 50 ml/min to more than 9 hours in subjects with reduced renal function < 50 ml/min.
Den nedsatte nyrefunktion ændrede dog ikke den perorale optagelse af lenalidomid.
However, renal impairment did not alter the oral absorption of lenalidomide.
4. 2.
Recommended dose adjustments in patients with impaired renal function are described in section 4.2.
Farmakokinetiske analyser baseret på studier med myelomatose viser, at lenalidomid absorberes hurtigt ved alle dosisniveauer med maksimale plasmakoncentrationer, som forekommer mellem 0, 5 og 4, 0 timer efter dosis på både dag 1 og 28.
Pharmacokinetic analyses based on multiple myeloma studies indicate that lenalidomide is rapidly absorbed at all dose levels, with maximum plasma concentrations occurring between 0.5 and 4.0 hours post-dose both on Days 1 and 28.
Cmax og AUC værdier stiger proportionelt med dosis efter enkelte og gentagne doser hos patienter med myelomatose.
The Cmax and AUC values increase proportionally with dose
Eksponeringen hos myelomatose- patienter er en smule højere baseret på Cmax og AUC- værdier sammenlignet med raske mandlige forsøgspersoner, da clearance - / biotilgængelighedsfraktionen af et lægemiddel (CL/ F) hos myelomatose- patienter er lavere (cirka 200 ml/ min sammenlignet med 300 ml/ min) end hos raske forsøgspersoner.
Exposure in multiple myeloma patients is slightly higher based on Cmax and AUC values as compared to healthy male volunteers since the clearance/bioavailable fraction of a drug (CL/F) in multiple myeloma patients is lower (approximately 200 ml/min compared to 300 ml/min) than it is in healthy volunteers.
Dette er i overensstemmelse med den nedsatte nyrefunktion hos patienterne med myelomatose, formentlig på grund af deres alder (gennemsnitlig patientalder på 58 vs.
This is consistent with the compromised renal function in the multiple myeloma patients, possibly as a consequence of their age (average patient age of 58 vs.
29 for raske forsøgspersoner) og deres sygdom.
29 for healthy volunteers) and their disease.
Der er blevet udført et forsøg angående embryoføtal udvikling med aber, som fik lenalidomid i doser på op til 4 mg/ kg/ dag.
An embryofoetal development study has been conducted in monkeys administered lenalidomide at doses up to 4 mg/kg/day.
Foreløbige fund fra dette igangværende forsøg viser, at lenalidomid forårsager misdannelser (forkortede ekstremiteter, bøjede fingre/ tæer, håndled og/ eller hale, for mange eller manglende fingre/ tæer) hos afkom af hunaber som har fået lægemidlet under graviditeten.
Preliminary findings from this on-going study showed that lenalidomide produced malformations (short limbs, bent digits, wrist and/or tail, supernumerary or absent digits) in the offspring of female monkeys who received the drug during pregnancy.
Thalidomid forårsagede samme type misdannelser i det samme forsøg.
Thalidomide produced similar types of malformations in the same study.
De dødelige minimumsdoser efter peroral administration var > 2000 mg/ kg/ dag hos gnavere.
Lenalidomide has a potential for acute toxicity; minimum lethal doses after oral administration were > 2000 mg/kg/day in rodents.
Gentagen peroral administration af 75, 150 og 300 mg/ kg/ dag til rotter i op til 26 uger gav en reversibel behandlingsrelateret stigning i nyre- bækken- mineralisering ved alle 3 doser, navnlig hos hunnerne.
Repeated oral administration of 75, 150 and 300 mg/kg/day to rats for up to 26 weeks produced a reversible treatment-related increase in kidney pelvis mineralisation in all 3 doses, most notably in females.
Niveauet uden observerede negative effekter (No observed adverse effect level, NOAEL) blev vurderet til at være mindre end 75 mg/ kg/ dag og er cirka 25 gange større end den humane, daglige eksponering baseret på AUC- eksponeringen.
The no observed adverse effect level (NOAEL) was considered to be less than 75 mg/kg/day, and is approximately 25-fold greater than the human daily exposure based on AUC exposure.
Gentagen peroral administration af 4 og 6 mg/ kg/ dag til aber i op til 20 uger forårsagede dødelighed og væsentlig toksicitet (udpræget vægttab, reduktion af røde og hvide blodlegemer og trombocyttal, blødning fra flere organer, inflammation af mavetarmkanalen, lymfom - og knoglemarvsatrofi).
Repeated oral administration of 4 and 6 mg/kg/day to monkeys for up to 20 weeks produced mortality and significant toxicity (marked weight loss, reduced red and white blood cell and platelet counts, multiple organ haemorrhage, gastrointestinal tract inflammation, lymphoid, and bone marrow atrophy).
Gentagen peroral administration af 1 og 2 mg/ kg/ dag til aber i op til 1 år fremkaldte reversible ændringer i knoglemarvens cellularitet, et let fald i forholdet mellem myeloide: erythroide celler og thymusatrofi.
Repeated oral administration of 1 and 2 mg/kg/day to monkeys for up to 1 year produced reversible changes in bone marrow cellularity, a slight decrease in myeloid:erythroid cell ratio and thymic atrophy.
Der blev observeret en svag suppression af antallet af hvide blodlegemer ved 1 mg/ kg/ dag, hvilket nogenlunde svarer til dosis hos mennesker på basis af AUC- sammenligninger.
Mild suppression of white blood cell count was observed at 1 mg/kg/day corresponding to approximately the same human dose based on AUC comparisons.
Mutagenicitets- studier in vitro (bakteriel mutation, humane lymfocytter, muselymfomer, Syrisk Hamster- fostercelle- transformation) og in vivo (mikronukleustest i rotter) viste ingen lægemiddel - relaterede virkninger på hverken gen - eller kromosom- niveau.
In vitro (bacterial mutation, human lymphocytes, mouse lymphoma, Syrian Hamster Embryo cell transformation) and in vivo (rat micronucleus) mutagenicity studies revealed no drug related effects at either the gene or chromosomal level.
Der er tidligere blevet gennemført udviklingsmæssige toksicitetsforsøg med kaniner.
Developmental toxicity studies were previously conducted in rabbits.
I disse forsøg fik kaninerne lenalidomid peroralt i doser på 3, 10 og 20 mg/ kg/ dag.
In these studies, rabbits were administered 3, 10 and 20 mg/kg/day orally.
En manglende mellemlap i lungerne blev observeret ved 10 og 20 mg/ kg/ dag afhængig af dosis, og fejlplacerede nyrer blev observeret ved 20 mg/ kg/ dag.
An absence of the intermediate lobe of the lung was observed at 10 and 20 mg/kg/day with dose dependence and displaced kidneys were observed at 20 mg/kg/day.
Variationer i bløddele og skeletter hos fostre sås ved 10 og 20 mg/ kg/ dag.
Soft tissue and skeletal variations in the foetuses were also observed at 10 and 20 mg/kg/day.
Vandfri lactose Mikrokrystallinsk cellulose Croscarmellosenatrium Magnesiumstearat
Lactose, anhydrous Cellulose, microcrystalline Croscarmellose sodium Magnesium stearate
Blæk til tryk:
Printing ink:
Shellac Propylenglycol Sort jernoxid (E172) Kaliumhydroxid
Shellac Propylene glycol Black iron oxide (E172) Potassium hydroxide
Må ikke opbevares ved temperaturer over 25°C.
Do not store above 25 C
Disse kapsler leveres i kartoner.
The capsules are provided in carton packs.
Hver karton indeholder tre polyvinylchlorid (PVC) / polychlorotrifluoroethylen (PCTFE) / aluminium- blister, hver med 7 kapsler.
Each pack contains three Polyvinylchloride (PVC) / Polychlorotrifluoroethylene (PCTFE) / Aluminium foil blisters, each with seven capsules.
Dette giver et samlet antal på 21 kapsler per pakning.
This gives a total of 21 capsules per pack.
Ikke anvendte lægemidler skal afleveres til apoteket.
Unused medicinal product should be returned to the pharmacist.
Celgene Europe Limited Riverside House Riverside Walk Windsor Berkshire SL4 1NA Storbritannien
Celgene Europe Limited Riverside House Riverside Walk Windsor Berkshire SL4 1NA United Kingdom
14, 06, 2007
14/06/2007
Hver kapsel indeholder 294 mg vandfri lactose.
Each capsule contains 294 mg of anhydrous lactose.
Blågrønne/ lysegule kapsler, der er mærket “ REV 10 mg ”.
Blue-green/pale yellow capsules marked “REV 10 mg”.
Behandling med lenalidomid må ikke påbegyndes, hvis det absolutte neutrofiltal < 1 x 109/ l og / eller trombocyttal < 75 x 109/ l eller, afhængig af infiltrationen af plasmaceller i rygmarven, thrombocyttal < 30 x 109/ l.
Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) < 1.0 x 109/l, and/or platelet counts < 75 x 109/l or, dependent on bone marrow infiltration by plasma cells, platelet counts < 30 x 109/l.
18 • Dosisreduktionstrin
17 • Dose reduction steps
19 patienter har nedsat nyrefunktion, skal dosis vælges med omhu, og det tilrådes at overvåge nyrefunktionen.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it would be prudent to monitor renal function.
Der kræves ingen dosisjusteringer for patienter med let nedsat nyrefunktion.
18 No dose adjustments are required for patients with mild renal impairment.
15 mg hver anden dag **
1 5 mg every other day**
Kriterier for, at kvinder ikke er fødedygtige En kvindelig patient eller en kvindelig partner af en mandlig patient betragtes som værende fødedygtig, medmindre hun opfylder mindst et af følgende kriterier: • Alder ≥ 50 år med naturlig amenorrhoea i ≥ 1 år * • Tidlig menopause bekræftet af en specialiseret gynækolog • Tidligere bilateral salpingo- ooforektomi eller hysterektomi • XY- genotype, Turner- syndrom, uterus- agenesi.
Criteria for women of non-childbearing potential A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: • Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year* • Premature ovarian failure confirmed by a specialist gynaecologist • Previous bilateral salpingo-oophorectomy, or hysterectomy • XY genotype, Turner syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential.
20 * Amenorrhoea som følge af cancerbehandling udelukker ikke fødedygtighed.
Counselling For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: • She understands the expected teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, 4 weeks before starting treatment, throughout the entire duration of treatment, and 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception