FrancophonIA/ELRC3.0 huggingface dataset:
English: • statins, for example simvastatin, pravastatin, rosuvastatin - used to lower blood cholesterol levels
Croatian: • statini, na primjer simvastain, pravastatin, rosuvastatin - koriste se za snižavanje razine kolesterola u krvi
English: Table 3 Summary of progression-free survival and overall survival: sBRCA mutated population in Study 19
Croatian: Tablica 3 Sažetak preživljenja bez progresije bolesti i ukupnog preživljenja: populacija sa somatskom BRCA mutacijom u ispitivanju 19
English: Multipack containing 112 (2 packs of 56) film-coated tablets.
Croatian: Višestruko pakiranje koje sadrži 112 (2 pakiranja od 56) filmom obloženih tableta.
English: Large rearrangements in the BRCA1/2 genes were detected in 7.4% (10/136) of the randomised patients.
Croatian: Velika preslagivanja u BRCA1/2 genima zabilježene su u 7,4% (10/136) randomiziranih bolesnica.
English: Therefore, caution should be exercised when sensitive CYP3A substrates or substrates with a narrow therapeutic margin (e.g. simvastatin, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, sirolimus, tacrolimus and quetiapine) are combined with olaparib.
Croatian: Stoga je potreban oprez kada se osjetljivi supstrati CYP3A ili supstrati s uskim terapijskim rasponom (npr. simvastatin, cisaprid, ciklosporin, ergot alkaloidi, fentanil, pimozid, sirolimus, takrolimus i kvetiapin) primjenjuju u kombinaciji sa olaparibom.
English: Median age was 56 years in both arms.
Croatian: Medijan godina u obje skupine bio je 56.
English: Baseline testing, followed by monthly monitoring of complete blood counts is recommended for the first 12 months of treatment and periodically after this time to monitor for clinically significant changes in any parameter during treatment which may require dose interruption or reduction and/or further treatment (see sections 4.2 and 4.4).
Croatian: Preporučuje se napraviti kompletnu krvnu sliku na početku liječenja, svaki mjesec tijekom prvih 12 mjeseci liječenja te periodički nakon toga, kako bi se nadzirale moguće klinički značajne promjene bilo kojeg parametra tijekom liječenja koje bi mogle zahtijevati privremeni prekid primjene, smanjenje doze i/ili daljnje liječenje (vidjeti dio 4.2 i 4.4).
English: Interval debulking surgery was performed in 35% of the patients and of these 82% had no macroscopic residual disease reported.
Croatian: Sekundarni kirurški zahvat radi smanjenja tumorske mase (engl. interval debulking) proveden je kod 35% bolesnica, od kojih 82% nije imalo makroskopski vidljivu rezidualnu bolest.
English: The proportion of patients who progressed within 6 months of the last dose of platinum-based chemotherapy was 3.5% for olaparib and 8.4% for placebo.
Croatian: Udio bolesnica kod kojih je progresija bolesti nastupila unutar 6 mjeseci od posljednje doze kemoterapije utemeljene na platini iznosio je 3,5% uz olaparib te 8,4% uz placebo.
English: There are no data from the use of olaparib in pregnant women, however, based on the mode of action of olaparib, Lynparza should not be used during pregnancy and in women of childbearing potential not using reliable contraception during therapy and for 1 month after receiving the last dose of Lynparza.
Croatian: Nema podataka o primjeni olapariba u trudnica, međutim, na temelju načina djelovanja olapariba Lynparza se ne smije primjenjivati tijekom trudnoće niti kod žena reproduktivne dobi koje ne koriste pouzdanu kontracepciju tijekom liječenja i još mjesec dana nakon primanja posljednje doze lijeka Lynparza.
English: Median time to first onset of anaemia was approximately 4 weeks (approximately 7 weeks for CTCAE grade ≥3 events).
Croatian: Medijan vremena do prve pojave anemije bio je otprilike 4 tjedna (otprilike 7 tjedana za CTCAE stupanj ≥ 3.).
English: The European Medicines Agency has waived the obligation to submit the results of studies with Lynparza in all subsets of the paediatric population, in ovarian carcinoma (excluding rhabdomyosarcoma and germ cell tumours) (see section 4.2 for information on paediatric use).
Croatian: Europska agencija za lijekove izuzela je obvezu podnošenja rezultata ispitivanja lijeka Lynparza u svim podskupinama pedijatrijske populacije u karcinomu jajnika (osim rabdomiosarkoma i tumora zametnih stanica) (vidjeti dio 4.2 za informacije o primjeni lijeka u pedijatrijskoj populaciji).
English: Olaparib 300 mg bd n=205
Croatian: Olaparib 300 mg 2x na dan n=205
English: At the time of the analysis of PFS the median duration of treatment was 19.4 months for olaparib and 5.6 months for placebo.
Croatian: U vrijeme analize PFS-a, medijan trajanja liječenja bio je 19,4 mjeseca za olaparib i 5,6 mjeseci za placebo.
English: • if you experience any new or worsening symptoms of shortness of breath, coughing or wheezing.
Croatian: • ako primijetite pojavu novih ili pogoršanje postojećih simptoma nedostatka zraka, kašlja ili piskanja pri disanju.
English: Frequency of All CTCAE grades
Croatian: Učestalost nuspojava svih stupnjeva prema CTCAE kriterijima
English: Treatment may be interrupted to manage adverse reactions such as nausea, vomiting, diarrhoea, and anaemia and dose reduction can be considered (see section 4.8).
Croatian: Liječenje se može privremeno prekinuti radi zbrinjavanja nuspojava poput mučnine, povraćanja, proljeva i anemije, a može se razmotriti i smanjenje doze (vidjeti dio 4.8).
English: Olaparib inhibited UGT1A1 in vitro, however, PBPK simulations suggest this is not of clinical importance.
Croatian: Olaparib je inhibirao UGT1A1 in vitro, ali PBPK (engl. physiologically based pharmacokinetic) simulacije pokazuju da to nije klinički važno.
English: In rat embryofoetal development studies, and at dose levels that did not induce significant maternal toxicity, olaparib caused reduced embryofoetal survival, reduced foetal weight and foetal developmental abnormalities, including major eye malformations (e.g. anophthalmia, microphthalmia), vertebral/rib malformation and visceral and skeletal abnormalities.
Croatian: U istraživanjima embriofetalnog razvoja na štakorima, i kod doza koje nisu izazvale značajnu toksičnost majke, olaparib je smanjio preživljenje embrija/fetusa i tjelesnu težinu ploda te je uzrokovao abnormalnosti u razvoju ploda, uključujući velike malformacije očiju (npr. anoftalmija, mikroftalmija), malformacije kralježaka/rebra te malformacije unutarnjih organa i kostura.
English: Vomiting events led to interruption in 10% of olaparib-treated patients; no olaparib-treated patients experienced a vomiting event leading to dose reduction.
Croatian: Povraćanje je dovelo do privremenog prekida liječenja kod 10% bolesnica liječenih olaparibom; nijednoj bolesnici liječenoj olaparibom nije smanjena doza zbog povraćanja.
English: Patients with hormone receptor (HR)-positive breast cancer should also have progressed on or after prior endocrine therapy, or be considered unsuitable for endocrine therapy.
Croatian: Bolesnici s rakom dojke pozitivnim na hormonski receptor (engl. hormone receptor, HR) morali su doživjeti progresiju bolesti tijekom ili nakon prethodne endokrine terapije ili se smatrati nepogodnima za endokrinu terapiju.
English: There are no efficacy or safety data on maintenance retreatment with Lynparza following first or subsequent relapse in ovarian cancer patients or on retreatment of breast cancer patients (see section 5.1).
Croatian: Nema podataka o djelotvornosti i sigurnosti ponovne terapije održavanja lijekom Lynparza nakon prvog ili sljedećeg relapsa kod bolesnica s karcinomom jajnika, kao ni o djelotvornosti i sigurnosti ponovnog liječenja bolesnika s rakom dojke (vidjeti dio 5.1).
English: TNBC gBRCA mutation type (%) gBRCA1 gBRCA2 gBRCA1 and gBRCA2 ≥2 Metastatic sites (%) Location of the metastasis (%) Bone only
Croatian: Trostruko negativan rak dojke Vrsta germinativne BRCA mutacije (%) gBRCA1 gBRCA2 gBRCA1 i gBRCA2 ≥ 2 metastatska sijela (%) Lokacija metastaze (%) Samo kost
English: Adverse reactions that most commonly led to dose interruptions and/ or reductions were anaemia (13.9%), vomiting (7.1%), nausea (6.6%), fatigue/asthenia (6.1%) and neutropenia (5.8%).
Croatian: Nuspojave koje su najčešće dovele do privremenog prekida primjene i/ili smanjenja doze bile su anemija (13,9%), povraćanje (7,1%), mučnina (6,6%), umor/astenija (6,1%) i neutropenija (5,8%).
English: You will be asked to take 200 mg (2 x 100 mg tablets)
Croatian: Liječnik će Vam reći da uzimate 200 mg (2 tablete od 100 mg)
English: The most common histological type was serous (96%), endometrioid histology was reported in 2% of the patients.
Croatian: Histološki je najčešći tip tumora bio serozni (96%), dok je endometrioidni tip prijavljen kod 2% bolesnica.
English: • Your doctor will tell you how many capsules of Lynparza to take.
Croatian: • Liječnik će Vam reći koliko kapsula lijeka Lynparza trebate uzeti.
English: At the time of the analysis of PFS the median duration of treatment was 8 months for olaparib and 4 months for placebo.
Croatian: U vrijeme analize PFS-a medijan trajanja liječenja bio je 8 mjeseci za olaparib i 4 mjeseca za placebo.
English: Number of events: Total number of patients (%)
Croatian: Broj događaja: ukupan broj bolesnica (%)
English: Patients were stratified based on: receipt of prior chemotherapy regimens for metastatic breast cancer (yes/no), hormone receptor (HR) positive vs triple negative (TNBC), prior platinum treatment for breast cancer (yes/no).
Croatian: Bolesnici su bili stratificirani na temelju prethodne primjene kemoterapije za liječenje metastatskog raka dojke (da/ne), pozitivnog nalaza testa na hormonski receptor (HR) naspram trostruko negativnog raka dojke te prethodnog liječenja platinom za rak dojke (da/ne).
English: Anaemia and other haematological toxicities were generally low grade (CTCAE grade 1 or 2), however, there were reports of CTCAE grade 3 and higher events.
Croatian: Anemija i druge hematološke toksičnosti obično su niskog stupnja (1. ili 2. stupnja prema CTCAE kriterijima), ali prijavljeni su i događaji ≥ 3. stupnja prema CTCAE kriterijima.
English: If you think any of these may apply to you, talk to your doctor, pharmacist or nurse before or during treatment with Lynparza.
Croatian: Ako mislite da bi se nešto od navedenoga moglo odnositi na Vas, obratite se svom liječniku, ljekarniku ili medicinskoj sestri prije ili tijekom liječenja lijekom Lynparza.
English: However, there was a slight reduction in embryofoetal survival.
Croatian: Međutim, zabilježeno je blago smanjenje preživljenja embrija/fetusa.
English: Patients were randomised into the study a median of 40 days after completing their final platinum chemotherapy.
Croatian: Bolesnice su bile randomizirane za sudjelovanje u ispitivanju 40 dana (medijan) nakon završetka posljednje kemoterapije platinom.
English: In cancers that lack functional components of HRR such as BRCA1 or 2, DNA DSBs cannot be repaired accurately or effectively.
Croatian: Kod karcinoma kod kojih nedostaju funkcionalne sastavnice potrebne za homolognu rekombinaciju, kao što su geni BRCA1 ili 2, dvolančani lomovi DNK ne mogu se pravilno ili učinkovito popraviti.
English: Co-administration with food slowed the rate (tmax delayed by 2 hours) and marginally increased the extent of absorption of olaparib (AUC increased by approximately 20%).
Croatian: Istodobna primjena s hranom usporila je brzinu apsorpcije olapariba (tmax je nastupio 2 sata kasnije) i marginalno povećala njezin opseg (AUC se povećao za približno 20%).
English: Each hard capsule contains 50 mg of olaparib.
Croatian: Jedna tvrda kapsula sadrži 50 mg olapariba.
English: Median TSST (months)
Croatian: Medijan TSST-a (mjeseci)
English: In the olaparib and placebo arms, 6% and 5% of patients had prior bevacizumab, respectively.
Croatian: U skupinama liječenim olaparibom i placebom, 6% i 5% bolesnica prethodno su primile bevacizumab.
English: Genetic counselling for patients tested for mutations in BRCA1/2 genes should be performed according to local regulations.
Croatian: Genetičko savjetovanje za bolesnike testirane na mutacije gena BRCA1/2 treba provoditi u skladu s lokalnim propisima.
English: Carcinogenicity Carcinogenicity studies have not been conducted with olaparib.
Croatian: Kancerogenost Nisu provedena ispitivanja kancerogenosti olapariba.
English: A benefit was also observed in patients with BRCA1/2 wild-type/variants of uncertain significance (BRCA1/2 wt/VUS), although of a lesser magnitude.
Croatian: BRCA wild-type/variants of uncertain significance , BRCA1/2 wt/VUS), iako u manjem opsegu.
English: Instead, alternative and error-prone pathways are activated, such as the classical non-homologous end joining (NHEJ) pathway, leading to increased genomic instability.
Croatian: Umjesto toga se aktiviraju drugi putovi kod kojih često dolazi do pogrešaka, poput klasičnog povezivanja nehomolognih krajeva (engl. non-homologous end joining, NHEJ), što povećava genomsku nestabilnost.
English: Lynparza is contraindicated during breast-feeding and for 1 month after receiving the last dose, given the pharmacologic property of the product (see section 4.3).
Croatian: Lynparza je kontraindicirana tijekom dojenja i još mjesec dana nakon uzimanja posljednje doze, s obzirom na farmakološka svojstva lijeka (vidjeti dio 4.3).
English: • herbal remedies containing St John's Wort (Hypericum perforatum) - used mainly for depression
Croatian: • biljne pripravke koji sadrže gospinu travu (Hypericum perforatum) - uglavnom se koristi za liječenje depresije
English: • phenytoin, carbamazepine, phenobarbital - used as a sedative or to treat fits (seizures) and epilepsy
Croatian: • fenitoin, karbamazepin, fenobarbital - koriste se za smirenje (sedaciju) te za liječenje napadaja i epilepsije
English: Pre-planned subgroup analysis by BRCA-mutation status identified patients with BRCA-mutated ovarian cancer (n=136, 51.3%) as the subgroup that derived the greatest clinical benefit from olaparib maintenance monotherapy.
Croatian: Unaprijed planirana analiza podskupina prema statusu mutacije BRCA gena pokazala je da su bolesnice oboljele od karcinoma jajnika s mutacijom BRCA gena (n=136; 51,3%) činile podskupinu koja je imala najveću kliničku korist od monoterapije održavanja olaparibom.
English: It is not known whether olaparib or its metabolites are found in seminal fluid.
Croatian: Nije poznato izlučuju li se olaparib ili njegovi metaboliti u sjemenu tekućinu.
English: In the placebo-treated group, 8.1% of patients remained on treatment for ≥2 years and 1.6% for ≥5 years.
Croatian: U skupini koja je primala placebo 8,1% bolesnica nastavilo je liječenje tijekom ≥ 2 godine, dok se njih 1,6% liječilo ≥ 5 godina.
English: Some of the patients had a history of previous cancer or of bone marrow dysplasia.
Croatian: Neki su bolesnici u povijesti bolesti imali prethodni rak ili displaziju koštane srži.
English: There is limited experience of overdose with olaparib.
Croatian: Iskustvo sa predoziranjem olaparibom je ograničeno.
English: Secondary efficacy endpoints included time from randomisation to second progression or death (PFS2), overall survival (OS), time from randomisation to discontinuation of treatment or death (TDT), time from randomisation to first subsequent anticancer therapy or death (TFST) and health related quality of life (HRQoL).
Croatian: Sekundarne mjere ishoda za djelotvornost uključivale su vrijeme od randomizacije do druge progresije bolesti ili smrti (PFS2), ukupno preživljenje (engl. overall survival, OS), vrijeme od randomizacije do prekida liječenja ili smrti (engl. time to discontinuation of treatment or death, TDT), vrijeme od randomizacije do prve sljedeće terapije za rak ili smrti (engl. time to first subsequent therapy or death, TFST) i kvalitetu života vezanu uz zdravlje (engl. health related quality of life, HRQoL).
English: After a number of rounds of replication, genomic instability can reach insupportable levels and result in cancer cell death, as cancer cells already have a high DNA damage load relative to normal cells.
Croatian: Nakon nekoliko replikacijskih ciklusa, genomska nestabilnost može poprimiti neodržive razmjere i dovesti do smrti karcinomske stanice, jer su karcinomske stanice već visoko opterećene oštećenjem DNK u odnosu na normalne stanice.
English: There are limited clinical data in patients aged 75 years and over.
Croatian: Klinički podaci o primjeni kod bolesnika u dobi od 75 i više godina su ograničeni.
English: Frequency of CTCAE grade 3 and above
Croatian: Učestalost nuspojava 3. i višeg stupnja prema CTCAE kriterijima
English: Due to the effect of food on olaparib absorption, patients should take Lynparza at least one hour after food, and refrain from eating preferably for up to 2 hours afterwards.
Croatian: Budući da hrana utječe na apsorpciju olapariba, bolesnice trebaju uzeti lijek Lynparza najmanje jedan sat nakon obroka te ne jesti po mogućnosti do 2 sata nakon toga.
English: The safety profile is based on pooled data from 1,826 patients with solid tumours treated with Lynparza monotherapy in clinical trials at the recommended dose.
Croatian: Sigurnosni profil temelji se na objedinjenim podacima prikupljenima kod 1826 bolesnica sa solidnim tumorima koje su u kliničkim ispitivanjima primale monoterapiju lijekom Lynparza u preporučenoj dozi.
English: Lynparza is a white, opaque, hard capsule, marked with “OLAPARIB 50 mg” and the AstraZeneca logo in black ink.
Croatian: Lynparza je bijela, neprozirna tvrda kapsula s oznakom „OLAPARIB 50 mg“ i logom tvrtke AstraZeneca otisnutima crnom tintom.
English: Olaparib inhibits CYP3A4 in vitro and is predicted to be a mild CYP3A inhibitor in vivo.
Croatian: Olaparib inhibira CYP3A4 in vitro i predviđa se da je slabi inhibitor CYP3A in vivo.
English: CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib.
Croatian: CYP3A4/5 su izoenzimi pretežno odgovorni za metabolički klirens olapariba.
English: A value <1 favours olaparib.
Croatian: Vrijednost <1 ide u korist olapariba.
English: • response to platinum chemotherapy, or
Croatian: • na temelju odgovora na kemoterapiju platinom
English: The incidence of MDS/AML cases was similar among gBRCA1m and gBRCA2m patients (1.7% and 1.4%, respectively).
Croatian: Incidencija slučajeva MDS-a/AML-a bila je slična među bolesnicima s gBRCA1 mutacijom i onima s gBRCA2 mutacijom (1,7% odnosno 1,4%).
English: Following oral administration of olaparib via the capsule formulation, absorption is rapid with peak plasma concentrations typically achieved between 1 to 3 hours after dosing.
Croatian: Nakon peroralne primjene olapariba u obliku kapsula, apsorpcija je brza, a vršne koncentracije u plazmi obično se postižu 1 do 3 sata nakon primjene doze.
English: Co-administration with food slowed the rate (tmax delayed by 2.5 hours and Cmax reduced by approximately 21%) but did not significantly affect the extent of absorption of olaparib (AUC increased 8%).
Croatian: Istodobna primjena s hranom usporila je brzinu apsorpcije olapariba (tmax je nastupio 2,5 sati kasnije, a Cmax se smanjio za približno 21%), ali to nije značajno utjecalo na njezin opseg (AUC se povećao za 8%).
English: Please note Lynparza is also available as a 50 mg capsule.
Croatian: Imajte na umu da je Lynparza dostupna i u obliku kapsule od 50 mg.
English: Do not switch to Lynparza tablets unless your doctor tells you
Croatian: Ne smijete početi uzimati Lynparza tablete ako Vam to nije rekao Vaš liječnik.
English: Figure 7 PFS (BICR), Forest plot, by prespecified subgroup
Croatian: Slika 7 PFS (prema ocjeni BICR-a) po unaprijed specificiranim podskupinama, grafikon raspona pouzdanosti
English: The limited data for these somatic tumour BRCA (sBRCA) mutated patients show that fewer patients on olaparib reported progression events or death events compared with placebo (Table 3).
Croatian: Ograničeni podaci za te bolesnice sa somatskom BRCA mutacijom u tumoru pokazuju da je kod manjeg broja bolesnica na olaparibu, u usporedbi s placebom, prijavljen događaj progresije ili smrtni ishod (Tablica 3).
English: There was no strategy for multiple testing in place for the sub-group analyses.
Croatian: Nije postojala strategija za višestruko testiranje u analizama podskupina.
English: (E172), iron oxide black (E172) (150 mg tablets only).
Croatian: crni željezov oksid (E172) (samo tablete od 150 mg)
English: PFS (DCO 30 June
Croatian: PFS (završni datum prikupljanja podataka: 30. lipnja
English: There are limited data in patients with somatic BRCA mutated tumours; 10 patients in the olaparib arm and 10 patients in the placebo arm were defined as having somatic BRCA1/2 mutation.
Croatian: Podaci o bolesnicama koje su imale tumore sa somatskim mutacijama BRCA gena su ograničeni; za 10 bolesnica u skupini liječenoj olaparibom i 10 bolesnica u skupini koje su primile placebo zaključeno je da su imale somatske BRCA1/2 mutacije.
English: Breast-feeding during treatment and 1 month after the last dose (see section 4.6).
Croatian: Dojenje tijekom liječenja i mjesec dana nakon zadnje doze (vidjeti dio 4.6).
English: The analysis was performed using a Cox proportional hazard model including response to previous platinum chemotherapy (CR or PR), and time to disease progression (>6-12 months and >12 months) in the penultimate platinum-based chemotherapy as covariates.
Croatian: Analiza je provedena uz primjenu Coxova modela proporcionalnog hazarda u kojem su kovarijante bile odgovor na prethodnu kemoterapiju platinom (CR ili PR) i vrijeme do progresije bolesti (>6-12 mjeseci i > 12 mjeseci) nakon pretposljednje kemoterapije utemeljene na platini.
English: What Lynparza is and what it is used for
Croatian: Što je Lynparza i za što se koristi
English: There are no data in patients with severe hepatic impairment (Child-Pugh classification C).
Croatian: Nema podataka o primjeni kod bolesnika s teškim oštećenjem jetrene funkcije (Child-Pugh klasifikacija C).
English: Baseline testing, followed by monthly monitoring, of complete blood counts is recommended for the first 12 months of treatment and periodically after this time to monitor for clinically significant changes in any parameter during treatment (see section 4.8).
Croatian: Preporučuje se napraviti kompletnu krvnu sliku na početku liječenja, svaki mjesec tijekom prvih 12 mjeseci liječenja te periodički nakon toga, kako bi se nadzirale moguće klinički značajne promjene bilo kojeg parametra tijekom liječenja (vidjeti dio 4.8).
English: Retrospective testing of patients with available tumour samples was performed using central testing and generated successful results in 341 patients, of which 95% had an eligible mutation (known [n=47] or likely pathogenic [n=277]) and 2 gBRCAwt patients were confirmed to have sBRCAm only.
Croatian: Retrospektivno testiranje bolesnica s dostupnim tumorskim uzorcima provedeno je primjenom centralnog testa; dobiveni su uspješni rezultati za 341 bolesnicu, od kojih je njih 95% imalo mutaciju koja ih je činila pogodnima za liječenje (patogenu [n=47] ili vjerojatno patogenu [n=277]), dok je kod 2 bolesnice s gBRCA divljim tipom potvrđena samo somatska BRCA mutacija.
English: In the olaparib and placebo arms, 17% and 20% of patients had prior bevacizumab, respectively.
Croatian: U skupinama liječenim olaparibom i placebom, 17% i 20% bolesnica prethodno su primile bevacizumab.
English: Adverse reactions that most commonly led to permanent discontinuation were anaemia (1.3%), nausea (0.8%) and thrombocytopenia (0.5%).
Croatian: Nuspojave koje su najčešće dovele do trajnog prekida liječenja bile su anemija (1,3%), mučnina (0,8%) i trombocitopenija (0,5%).
English: Data from a double-blind placebo-controlled study showed median increase up to 23% from baseline remaining consistent over time and returning to baseline after treatment discontinuation, with no apparent clinical sequelae.
Croatian: Podaci iz dvostruko slijepog, placebom kontroliranog ispitivanja ukazali su na medijan porasta početne vrijednosti za do 23%, koji je bio postojan tijekom vremena, a vratio se na početnu vrijednosti nakon prekida liječenja, bez primjetnih kliničkih posljedica.