natgillin/translations-raw huggingface dataset:
Patienter, som overholder alle de følgende kriterier: • Ingen egn på blaster i kredsløb eller ekstramedullær sygdom • M1- knoglemarv (≤ 5% blaster) • Det perifere blodbillede normaliseret (trombocyttal ≥ 100 x 109/ l og ANC ≥ 1, 0 x 109/ l)
Patients who met each of the following criteria: • No evidence of circulating blasts or extramedullary disease • An M1 bone marrow (≤ 5% blasts) • Recovery of peripheral counts (platelets ≥ 100 x 109/ l and ANC ≥ 1.0 x 109/ l)
CRp = Komplet remission uden fuldstændig normalisering af trombocyttal PR = Partiel remission
CRp = Complete Remission in the Absence of Total Platelet Recovery PR = Partial Remission
• Patienter, der overholder alle kriterierne for CR undtagen normalisering af trombocyttal (> 100 x 109/ l Patienter, som overholder alle de følgende kriterier: • Blaster fuldstændig forsvundet fra kredsløb • M2- knoglemarv (≥ 5% og ≤ 25% blaster) – udseende som for normale progenitorceller • M1- knoglemarv, der ikke kunne henregnes til CR eller CRp
• Patients who met all of the criteria for a CR except for recovery of platelet counts to > 100 x 109/ l Patients who met each of the following criteria: • Complete disappearance of circulating blasts • An M2 bone marrow (≥ 5% and ≤ 25% blasts) and appearance of normal progenitor cells • An M1 marrow that did not qualify for CR or CRp
• (Antal patienter med CR + antal patienter med CRp) - antal valgbare patienter, der fik clofarabin
• (Number of patients with a CR + Number of patients with a CRp) ÷ Number of eligible patients who received clofarabine
Clofarabins sikkerhed og effekt blev evalueret i et fase I, åbent, non- komparativt dosiseskalerings - forsøg med 25 pædiatriske patienter med recidiverende eller refraktær leukæmi (17 ALL, 8 AML), som ikke havde opnået bedring med standardbehandling, eller som ikke kunne få anden behandling.
The safety and efficacy of clofarabine were evaluated in a phase I, open-label, non-comparative, dose-escalation study in 25 paediatric patients with relapsed or refractory leukaemia (17 ALL; 8 AML) who had failed standard therapy or for whom no other therapy existed.
Administration begyndte med en dosis på 11, 25 og eskalerede til 15, 30, 40, 52 og 70 mg / m2/ dag som intravenøs infusion i 5 dage hver 2. – 6. uge afhængigt af toksicitet og respons.
Dosing commenced at 11.25 with escalation to 15, 30, 40, 52 and 70 mg/ m2/ day by intravenous infusion for 5 days every 2 to 6 weeks depending on toxicity and response.
Tretten af disse patienter (9 ALL, 4 AML) fik et behandlingsregime, der bestod af clofarabin 52 mg/ m2/ dag.
Thirteen of these patients (9 ALL, 4 AML) were treated with the 52 mg/ m2/ day clofarabine regimen.
Ud af de 17 ALL- patienter opnåede 4 komplet remission (24%, CR) og 1 partiel remission (6%, PR) med forskellige doser.
Of the 17 ALL patients, 4 achieved a complete remission (24%; CR) and 1 a partial remission (6%; PR) at varying doses.
4. 9).
Dose-limiting toxicities in this study were hyperbilirubinaemia, elevated transaminase levels and maculo-papular rash experienced at 70 mg/ m2/ day (2 ALL patients; see section 4.9).
Et fase II -, åbent, non- komparativt multicenterforsøg med clofarabin blev udført for at bestemme total remission (TR) hos tungt behandlede patienter (≤ 21 år ved første diagnosticering) med recidiverende eller refraktær ALL defineret i henhold til fransk- amerikansk- britisk klassifikation.
A multi-centre, phase II, open-label, non-comparative study of clofarabine was conducted to determine the overall remission (OR) rate in heavily pretreated patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL defined using the French-American-British classification.
Den maksimale tolererede dosis clofarabin identificeret i det ovenfor beskrevne fase I- forsøg, 52 mg/ m2/ dag, blev administreret som intravenøs infusion 5 dage i træk hver 2. – 6. uge.
9 administered by intravenous infusion for 5 consecutive days every 2 to 6 weeks.
Forsøgets hovedresultater for effekt gengives i tabellen nedenfor.
The table below summarises the key efficacy results for this study.
Patienter med ALL måtte ikke være egnet til behandling med et større kurativt potentiale og skulle være nået til andet eller senere recidiv og/ eller være refraktære, d. v. s. de havde ikke opnået remission efter mindst de sidste to regimer.
Patients with ALL must not have been eligible for therapy of higher curative potential and must have been in second or subsequent relapse and/ or refractory i. e. failed to achieve remission after at least two prior regimens.
9 4 forskellige induktionsregimer, og 18/ 61 (30%) af disse patienter havde fået mindst 1 tidligere hæmatologisk stamcelletransplantation (HSCT).
Before enrolling in the trial, 58 of the 61 patients (95%) had received 2 to 4 different induction regimens and 18/ 61 (30%) of these patients had undergone at least 1 prior haematological stem cell transplant (HSCT).
Administration af clofarabin medførte en dramatisk og hurtig reduktion af perifere leukæmiceller hos 31 ud af de 33 patienter (94%), som havde et måleligt absolut blasttal ved baseline.
Administration of clofarabine resulted in a dramatic and rapid reduction in peripheral leukaemia cells in 31 of the 33 patients (94%) who had a measurable absolute blast count at baseline.
De 12 patienter, som opnåede total remission (CR + CRp) havde en median overlevelsestid på 66, 6 uger ved skæringspunktet for dataindsamling.
The 12 patients who achieved an overall remission (CR + CRp) had a median survival time of 66.6 weeks as of the data collection cut-off date.
Respons sås hos forskellige immunfænotyper af ALL, inklusive præ- B- celle - og T- celle- ALL.
Responses were seen in different immunophenotypes of ALL, including pre-B cell and T-cell.
Selv om forekomst af transplantationer ikke var et af forsøgets endepunkter, fik 10/ 61 patienter (16%) HSCT efter behandling med clofarabin (af disse havde 3 opnået CR og 2 CRp, 3 havde opnået PR, 1 patient blev af IRRP henregnet under behandlingssvigt, og 1 blev af IRRP anset for ikke- evaluerbar.
Although transplantation rate was not a study endpoint, 10/ 61 patients (16%) went on to receive a HSCT after treatment with clofarabine (3 after achieving a CR, 2 after a CRp, 3 after a PR, 1 patient that was considered a treatment failure by the IRRP and 1 that was considered not evaluable by the IRRP).
Hovedforsøgets effektresultater hos patienter (≤ 21 år ved første diagnosticering) med recidiverende eller refraktær ALL efter mindst to forudgående behandlingsregimer Responskategori
Efficacy results from the pivotal study in patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL after at least two prior regimens Response
ITT -
ITT*
Median varighed af
Median duration of
Median tid til
Median time to
Median total
Median overall
patiente r *
category
remission (uger) (95%
remission (weeks) (95% CI)
progression (uger) ** (95%
progression (weeks)** (95% CI)
overlevelse (uger) (95%
survival (weeks) (95% CI)
(CR + CRp) CR
Overall remission (CR + CRp) CR
(20%) 7
12 (20%) 7 (12%)
(15, 4 til 58, 6) 56, 1
28.6 (9.7 to 58.6) 47.9 (6.1 to -)
(53, 7 til 89, 4) 66, 6
37.0 (15.4 to 61.9) 56.1 (13.7 to -)
(66, 6 til 89, 4)
66.6 (53.7 to 89.4) 66.6 (66.6 to 89.4)
CRp
CRp
5
5 (8%)
(4, 6 til 35, 4)
28.6 (4.6 to 35.4)
(9, 1 til 39, 4)
37.0 (9.1 to 39.4)
(9, 1 til -)
53.7 (9.1 to -)
(2, 3 til -)
5.2 (2.3 to -)
(6, 3 til -)
8.6 (6.3 to -)
(18, 1 til -)
33.0 (18.1 to -)
(6, 1 til 47, 9) Intet svar
11.7 (6.1 to 47.9) N/ A
(10, 6 til 56, 1) 4, 0
20.4 (10.6 to 56.1) 4.0
(42, 0 til 89, 4) 7, 6
66.6 (42.0 to 89.4) 7.6
Intet svar
N/ A
(3, 4 til 5, 1)
(3.4 to 5.1)
(6, 7 til 12, 6)
(6.7 to 12.6)
(4, 0 - 6, 1)
5.4 (4.0 to 6.1)
(7, 9 - 18, 1)
12.9 (7.9 to 18.1)
* ITT = intention to treat ** Patienter, der var i live og i remission på tidspunktet for sidste opfølgning, indgik på dette tidspunkt i analysen.
*ITT = intention to treat. **Patients alive and in remission at the time of last follow up were censored at that time point for the analysis.
Klinisk sikkerhed Se pkt.
Clinical safety:
4. 8.
See section 4.8.
5. 1).
The patients were enrolled into a single phase I (n = 12) or two phase II (n = 14 / n = 14) safety and efficacy studies, and received multiple doses of clofarabine by intravenous infusion (see section 5.1).
Farmakokinetikken hos patienter mellem 2 og 19 år med recidiverende eller refraktær ALL eller AML efter administration af gentagne doser clofarabin som intravenøs infusion Parameter
10 Pharmacokinetics in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML following administration of multiple doses of clofarabine by intravenous infusion Parameter
Estimater baseret på non - kompartmental analyse
Estimates based on
baseret på anden analyse
Estimates based on other
10 (n = 14 / n = 14)
non-compartmental analysis (n = 14 / n = 14)
Fordelingsvolumen (steady- state) Plasmaproteinbinding Serum- albumin Elimination:
Volume of distribution (steady state) Plasma protein binding Serum albumin Elimination:
47, 1% 27, 0%
47.1% 27.0%
Clofarabins β- halveringstid Clofarabintriphosphats halveringstid Systemisk clearance Renal clearance Dosis udskilt med urinen
5.2 hours
5, 2 timer 28, 8 l/ time/ m2 10, 8 l/ time/ m2 57%
Half-life of clofarabine triphosphate
En multivariatanalyse viste, at clofarabins farmakokinetik er vægtafhængig, og selvom det fremgik, at leukocyttallet påvirker clofarabins farmakokinetik, syntes dette ikke at være tilstrækkeligt til at fastsætte den enkelt patients behandlingsregime ud fra vedkommendes leukocyttal.
Multivariate analysis showed that the pharmacokinetics of clofarabine are weight dependent and although white blood cell (WBC) count was identified as having an impact on clofarabine pharmacokinetics, this did not appear sufficient to individualise a patient’ s dosage regimen based on their WBC count.
Intravenøs infusion af clofarabin 52 mg/ m2 gav samme eksponering inden for et stort vægtområde.
Intravenous infusion of 52 mg/ m2 clofarabine produced equivalent exposure across a wide range of weights.
4. 2).
Accordingly, longer infusion times should be considered in children weighing < 20 kg (see section 4.2).
Clofarabin elimineres via en kombination af renal og ikke- renal udskillelse.
Clofarabine is eliminated by a combination of renal and non-renal excretion.
Efter 24 timer er omkring 60% udskilt uomdannet med urinen.
After 24 hours, about 60% of the dose is excreted unchanged in the urine.
Da clofarabin imidlertid ikke metaboliseres af cytochrom P450 - (CYP -) enzymsystemet, er de renale eliminationsprocesser aktuelt ikke afdækket.
However, as clofarabine is not detectably metabolised by the cytochrome P450 (CYP) enzyme system, pathways of non-renal elimination currently remain unknown.
Voksne (> 21 og < 65 år):
Adults (> 21 and < 65 years old):
Imidlertid blev clofarabins farmakokinetik hos voksne med recidiverende eller refraktær AML efter administration af en enkelt dosis clofarabin på 40 mg / m2 givet som intravenøs infusion over 1 time sammenlignet med farmakokinetikken beskrevet ovenfor hos patienter mellem 2 og 19 år med recidiverende eller refraktær ALL eller AML efter administration af clofarabin 52 mg/ m2 som intravenøs infusion over 2 timer 5 dage i træk.
However, the pharmacokinetics of clofarabine in adults with relapsed or refractory AML following administration of a single dose of 40 mg/ m2 clofarabine by intravenous infusion over 1 hour were comparable to those described above in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML following administration of 52 mg/ m2 clofarabine by intravenous infusion over 2 hours for 5 consecutive days.
Ældre patienter (> 65 år):
Elderly patients (≥ 65 years old):
Erfaringsgrundlaget er endnu utilstrækkeligt til at påvise sikkerhed og effekt af clofarabin til ældre patienter.
There are currently insufficient data to establish the safety and efficacy of clofarabine in elderly patients.
4. 3 og 4. 4).
There is no experience in patients with renal insufficiency (serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys (see sections 4.3 and 4.4).
Der foreligger endnu utilstrækkelige data om clofarabins farmakokinetik hos patienter med nedsat kreatininclearance til at kunne anbefale dosisreduktion hos denne patientgruppe.
To date, there are limited data on the pharmacokinetics of clofarabine in patients with decreased creatinine clearance.
4. 2 og 4. 4).
However, these data indicate that clofarabine may accumulate in such patients (see figure below and sections 4.2 and 4.4).
11 Clofarabins AUC0- 24 timer for kreatininclearance bestemt ved baseline hos patienter i mellem 2- 19 år med recidiverende eller refraktær ALL eller AML (n = 11 / n = 12) efter administration af gentagne doser af clofarabin som intravenøs infusion (Kreatininclearance bestemt i henhold til Schwartz’ s formel) 3000
11 Clofarabine AUC0-24 hours by baseline estimated creatinine clearance in patients aged between 2 to 19 years old with relapsed or refractory ALL or AML (n = 11 / n = 12) following administration of multiple doses of clofarabine by intravenous infusion (Creatinine clearance estimated using Schwartz formula) 3000
Clofarabin
Clofarabine
AUC
AUC 0-24 hours
0- 24 timer
(ng*h/ ml)
(ng* timmar/ ml) 2000
2000
Skønnet kreatininclearance (ml/ min)
Estimated creatinine clearance (ml/ min)
4. 3 og 4. 4).
There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity (see sections 4.3 and 4.4).
7- 13 gange (efter mindst 3 behandlingscykler) eller 16- 35 gange (efter en til flere behandlingscykler) højere end klinisk eksponering.
They were reported at exposure levels (Cmax) approximately 7 to 13 fold (after 3 or more dosing cycles) or 16 to 35 fold (after one or more dosing cycles) higher than clinical exposures.
Den mindste virkning observeret ved lavere doser tyder på, at der er en tærskel for hjertetoksicitet, og non- lineær plasmafarmakokinetik hos rotter kan medvirke til de observerede virkninger.
The minimal effects seen at lower doses suggest that there is a threshold for toxicities on the heart and nonlinear plasma pharmacokinetics in the rat may play a role in the observed effects.
Glomerulonefropati rapporteredes hos rotter efter 3- 5 gange større eksponering end det kliniske AUC efter 6 behandlingscykler med clofarabin.
Glomerulonephropathy was reported in rats at exposure levels 3 to 5 fold higher than the clinical AUC after 6 dosing cycles of clofarabine.
Histologisk dokumentation af leverpåvirkning sås hos hunde efter akut administration af høje doser, men det var heller ikke ledsaget af forandringer i serum - værdier.
Histological evidence of hepatic effects was seen in dogs following acute administration of high doses, but was also not accompanied by changes in serum chemistry.
Disse virkninger omfattede bilateral degeneration af epitel i tubuli seminiferi med retention af spermatider og atrofi af interstitielle celler hos rotter ved meget høje eksponeringsniveauer af clofarabin (150 mg/ m2/ dag), og celledegeneration i epididymis samt degeneration af epitel i tubuli seminiferi hos hunde ved klinisk relevant eksponeringsniveauer (> 7, 5 mg/ m2/ dag).
These effects included bilateral degeneration of the seminiferous epithelium with retained spermatids and atrophy of interstitial cells in rats at exaggerated exposure levels (150 mg/ m2/ day), and cell degeneration of the epididymis and degeneration of the seminiferous epithelium in dogs at clinically relevant exposure levels (> 7.5 mg/ m2/ day clofarabine).
12 Forsinket ovarieatrofi eller degeneration og apoptose i endometriet optrådte hos hunmus ved den eneste anvendte dosis clofarabin på 225 mg/ m2/ dag.
12 Delayed ovarian atrophy or degeneration and uterine mucosal apoptosis were observed in female mice at the only dose used of 225 mg/ m2/ day clofarabine.
2- 3 gange den kliniske eksponering (54 mg/ m2/ dag), og hos kaniner, der fik 12 mg/ m2/ dag.
Increases in postimplantation loss, reduced foetal body weights and decreased litter sizes together with increases in the number of malformations (gross external, soft tissue) and skeletal alterations (including retarded ossification) were reported in rats receiving doses which produced approximately 2 to 3 fold the clinical exposure (54 mg/ m2/ day) and in rabbits receiving 12 mg/ m2/ day clofarabine.
Grænsen for udviklingstoksicitetsforsøg ansås at være 6 mg/ m2/ dag hos rotter og 1, 2 mg/ m2/ dag hos kaniner.
(There are no exposure data in rabbits.) The threshold for developmental toxicity was considered to be 6 mg/ m2/ day in rats and 1.2 mg/ m2/ day in rabbits.
Det ikke- observerbare effektniveau for maternel toksicitet hos rotter var 18 mg/ m2/ dag, mens det hos kaniner var over 12 mg/ m2/ dag.
The no-observable effect level for maternal toxicity in rats was 18 mg/ m2/ day and in rabbits was more than 12 mg/ m2/ day.
Genotoksicitetsforsøg viste, at clofarabin ikke var mutagent i en tilbagemutationstest med bakterier, men var klastogent i en ikke- aktiveret kromosomal aberrationstest af ovarieceller fra kinesiske hamstere og i en in vivo- mikronukleustest hos rotter.
Genotoxicity studies demonstrated that clofarabine was not mutagenic in the bacterial reverse mutation assay, but did induce clastogenic effects in the non-activated chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells and in the in vivo rat micronucleus assay.
Det fortyndede sterile koncentrat holder sig fysik og kemisk stabilt i 3 dage ved 2ºC - 8º C og ved stuetemperatur.
The diluted sterile concentrate is chemically and physically stable for 3 days at 2 to 8°C and at room temperature.
Hvis det ikke anvendes umiddelbart, er brugeren ansvarlig for opbevaringstid og - betingelser før brug, som normalt ikke må overstige 24 timer ved 2ºC - 8ºC, med mindre fortynding har fundet sted under kontrollerede og validerede aseptiske betingelser.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C unless dilution has taken place under controlled and validated aseptic conditions.
20 ml hætteglas af type I- glas med brombutyl gummiprop, flip- off plombering af polypropylen og aluminiumsforsegling.
20 ml, Type I glass vial with bromobutyl rubber stopper, polypropylene flip-off cap and aluminium overseal.
Hvert af hætteglassene indeholder 20 ml sterilt koncentrat, og de er pakket i en æske.
The vials contain 20 ml sterile concentrate and are packaged in a box.
Hver æske indeholder 3, 4, 10 eller 20 hætteglas.
Each box contains 3, 4, 10 or 20 vials.
13 6. 6 Regler for destruktion og anden håndtering
13 6.6 Special precautions for disposal and other handling
Evoltra 1 mg/ ml koncentrat til infusion, opløsning, skal fortyndes før administration.
Evoltra 1 mg/ ml concentrate for solution for infusion must be diluted prior to administration.
Opløsningen filtreres gennem et sterilt 0, 2 µm sprøjtefilter og fortyndes så med 9 mg/ ml (0, 9%) natriumchlorid til fortynding af infusionskoncentrat, så der opnås et samlet volumen som angivet i eksemplerne på tabellen nedenfor.
It should be filtered through a sterile 0.2 micrometre syringe filter and then diluted with sodium chloride 9 mg/ ml (0.9%) intravenous infusion to produce a total volume according to the examples given in the table below.
Volumenet af den færdige opløsning kan dog variere noget afhængigt af patientens kliniske status og lægens skøn.
However, the final dilution volume may vary depending on the patient’ s clinical status and physician discretion.
(Hvis det ikke er muligt at anvende et 0, 2 µm sprøjtefilter, skal det sterile koncentrat forfiltreres gennem et 5 µm filter, fortyndes og dernæst administreres gennem et 0, 22 µm in- line filter).
(If the use of a 0.2 micrometre syringe filter is not feasible, the sterile concentrate should be pre-filtered with a 5 micrometre filter, diluted and then administered through a 0.22 micrometre in-line filter.)
Forslag til fortynding baseret på den anbefalede dosering af 52 mg/ m2/ dag clofarabin
Suggested dilution schedule based on the recommended dosage of 52 mg/ m2/ day clofarabine
Legemsoverflade (m2) ≤ 1, 44 1, 45 - 2, 40 2, 41 – 2, 50
Body surface area (m2) ≤ 1.44 1.45 to 2.40 2.41 to 2.50
Sterilt koncentrat (ml) * ≤ 74, 9 75, 4 – 124, 8 125, 3 – 130, 0
Sterile concentrate (ml)* ≤ 74.9 75.4 to 124.8 125.3 to 130.0
Total fortyndingsvolumen 100 ml 150 ml 200 ml
Total diluted volume 100 ml 150 ml 200 ml
* 1 ml koncentrat indeholder 1 mg clofarabin.
*Each ml of concentrate contains 1 mg of clofarabine.
Til en patient med legemsoverflade ≤ 0, 38 m2 skal der derfor kun anvendes en del af indholdet i et enkelt hætteglas til at fremstille den anbefalede døgndosis clofarabin.
Therefore, for patients with a body surface area ≤ 0.38 m2, the partial contents of a single vial will be required to produce the recommended daily dosage of clofarabine.
Til en patient med legemsoverflade > 0, 38 m2 vil der imidlertid være behov for at anvende indholdet fra 1- 7 hætteglas til at fremstille den anbefalede døgndosis clofarabin.
However, for patients with a body surface area > 0.38 m2, the contents of between 1 to 7 vials will be required to produce the recommended daily dosage of clofarabine.
Det fortyndede sterile koncentrat skal fremstå som en klar, farveløs opløsning.
The diluted sterile concentrate should be a clear, colourless solution.
Denne opløsning skal kontrolleres visuelt for partikelindhold og misfarvning før administration.
Visually inspect for particulate matter and discolouration prior to administration.
Ikke anvendt opløsning skal bortskaffes.
Any unused product must be discarded.
Genzyme Europe BV Gooimeer 10 1411DD Naarden Holland
Genzyme Europe BV Gooimeer 10 1411DD Naarden The Netherlands
Tlf: +31 (0) 35 699 12 00 Fax: +31 (0) 35 694 32 14
Tel: +31 (0)35 699 12 00 Fax: +31 (0) 35 694 32 14
14 9.
14 8.
Maj 2006
29 May 2006.
FREMSTILLERE AF DET BIOLOGISK AKTIVE STOF OG FREMSTILLERE ANSVARLIG FOR BATCHFRIGIVELSE
MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
Penn Pharmaceutical Services Limited Tafarnaubach Industrial Estate Tredegar Gwent NP22 3AA Storbritannien
Penn Pharmaceutical Services Limited Tafarnaubach Industrial Estate Tredegar Gwent NP22 3AA United Kingdom
Pharmachemie B. V (PCH) Swensweg 5 Haarlem Holland
Pharmachemie B. V (PCH) Swensweg 5 Haarlem The Netherlands
Resultaterne af undersøgelserne vil danne grundlaget for den årlige revurdering af risk/ benefit- forholdet.
The Marketing Authorisation Holder (MAH) shall complete the following programme of studies within the specified time frame, the results of which shall form the basis of the annual reassessment of the benefit/ risk profile.
Kliniske aspekter 1.
Clinical aspects 1.
MAH har forpligtet sig til at udarbejde data fra en farmakokinetisk populationsanalyse af clofarabin- koncentrationer til børn og voksne samt andre data, der vil understøtte en anbefaling om dosisjusteringer til patienter med moderat nyreinsufficiens, inden den 31. marts 2009.
The MAH has committed to provide data from a population PK analysis of paediatric and adult clofarabine concentrations, as well as additional data, which will support a recommendation of dose adjustments in patients with moderate renal impairment, by 31 March 2009.
MAH vil inden denne dato desuden overveje behovet for yderligere et klinisk forsøg.
The MAH will also consider the need for an additional clinical study, by this date.
MAH har forpligtet sig til at monitorere for og indberette toksicitet i alle igangværende og planlagte kliniske afprøvninger.
The MAH has committed to monitor and report toxicity in all ongoing and planned clinical trials.
Indehaveren af markedsføringstilladelse vil fremsende periodiske rapporter til opdatering af sikkerheden (PSUR) med de fastsatte standardintervaller.
The marketing authorisation holder will provide updates in accordance with standard PSUR timings.
Forfaldsdag:
Due date:
Standardintervaller for PSUR.
Standard PSUR timings.