31 research outputs found

    Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial

    No full text
    Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600mg once daily (QD), ALV 800mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received 31weeks of randomized treatment; patients completed 48weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P0.0131), with highest cEVR rate seen with ALV 400mg BID (74% vs 36% with PR alone; P40weeks of randomized treatment, the SVR12 rate was 89% for ALV 400mg BID vs 30% for PR alone (P=0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents

    Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

    No full text
    Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. Results A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Conclusions Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens

    Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-na\uefve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

    No full text
    BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-\u3b12a and ribavirin (PR) in treatment-na\uefve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received 6512 weeks and 20% had received 6524 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-na\uefve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens

    Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial

    No full text
    Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600mg once daily (QD), ALV 800mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received 31weeks of randomized treatment; patients completed 48weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P0.0131), with highest cEVR rate seen with ALV 400mg BID (74% vs 36% with PR alone; P40weeks of randomized treatment, the SVR12 rate was 89% for ALV 400mg BID vs 30% for PR alone (P=0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents

    Biology and biotechnology of Trichoderma

    Get PDF
    Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications

    Interakcije nekih plijesni i aflatoksinogenog soja Asspergillus flavus NRRL 3251

    Get PDF
    The objective of this study was to evaluate biotic interaction between some mould species and active producer of aflatoxin B1 Aspergillus flavus NRRL 3251, co-cultured in yeast-extract sucrose (YES) broth. Twenty-five mould strains of Alternaria spp., Cladosporium spp., Mucor spp., A. flavus and A. niger, used as biocompetitive agents, were isolated from outdoor and indoor airborne fungi, scrapings of mouldy household walls, and from stored and post-harvest maize. Aflatoxin B1 was extracted from mould biomasses with chloroform and detected using the multitoxin TLC method. The results confirm antagonistic interaction between all strains tested. With Alternaria spp. and Cladosporium spp., aflatoxin B1 production decreased 100 %, compared to detection in a single culture of A. flavus NRRL 3251 (Cmean=18.7 µg mL-1). In mixed cultures with Mucor spp., aflatoxin B1 levels dropped to (5.6-9.3) µg mL-1, and the inhibition was from 50 % to 70 %. Four of five aflatoxin non-producing strains of A. flavus interfered with aflatoxin production in mixed culture, and reduced AFB1 productivity by 100 %. One strain showed a lower efficacy in inhibiting AFB1 production (80 %) with a detectable amount of AFB1 3.7 µg mL-1 when compared to control. A decrease in toxin production was also observed in dual cultivation with A. niger strains. It resulted in 100 % reduction in three strains), 90 % reduction in one strain (Cmean=1.9 µg mL-1) and 80 % reduction in one strain (Cmean=3.7 µg mL-1) inhibition.Cilj rada bio je procijeniti biotske interakcije između sojeva različitih vrsta plijesni i kontrolnog soja Aspergillus flavus NRRL 3251, producenta aflatoksina B1 (AFB1). Inhibitorno djelovanje u miješanim kulturama na tvorbu AFB1 ispitano je na dvadeset pet sojeva Alternaria, Cladosporium, Mucor i Aspergillus vrsta izoliranih iz zraka, strugotina pljesnivih zidova te uskladištenog i prezimljenog kukuruza. Biosinteze su provedene u tekućoj hranjivoj podlozi s kvaščevim ekstraktom (YESbujon). Ekstrakcije AFB1 iz biomase izvršene su multitoksinskom metodom tankoslojne kromatografije. Rezultati biotskih interakcija pokazali su antagonistički odnos svih testiranih sojeva. Alternaria i Cladosporium vrste simultano inokulirane sporama A. flavus NRRL 3251 inhibirale su tvorbu AFB1 100 % u odnosu na dokazani toksin u kontrolnoj biosintezi (konc. 18,7 µg mL-1). U miješanim kulturama vrstama roda Mucor dokazane su padajuće koncentracije AFB1 (9,3 µg mL-1, 7,5 µg mL-1 i 5,6 µg mL-1), odnosno inhibicija tvorbe toksina 50 % do 70 %. Atoksinogeni sojevi A. flavus inhibirali su tvorbu AFB1 80 % (1 soj, konc. 3,7 µg mL-1) i 100 % (4 soja). Antagonističko djelovanje prema toksinogenom soju, smanjujući tvorbu AFB1 u rasponu 80 % do 100 % (konc. 1,9 µg mL-1 i 3,7 µg mL-1), dokazano je u uzgojnim biosintezama s A. niger

    Clinical effects of erdosteine in the treatment of acute respiratory tract diseases in children

    No full text
    Erdosteine has positive effects on mucus rheology and transport due to the active metabolite (Metabolite 1) which contains a free thiol group. Erdosteine inhibits bacterial adhesiveness and has antioxidant properties. A synergistic effect of erdosteine with various antibiotics has been demonstrated in pharmacological and clinical studies. The present study was multicenter, randomized, double-blind and placebo-controlled. The aims of the study were to compare a combination of erdosteine with amoxicillin against an amoxicillin-placebo combination in pediatric patients with acute lower respiratory tract disease. A total of 158 patients (78 in the erdosteine group and 80 in the placebo group) were treated for 7 2 days. The efficacy parameters were cough (primary), polypnea, rhonchi, rales and body temperature (all measured at baseline, on Day 3 and at the end of treatment). Safety was assessed by strictly monitoring the occurrence of adverse events and using standard laboratory parameters. The results of the intention-to-treat analysis showed that the severity of cough was decreased by 47% at Day 3 in the erdosteine group with a statistically significant difference compared to placebo, the difference was still significant at the final visit. The decrease in the severity of rales was significantly greater at Day 3 in the erdosteine group than in the placebo group. The incidence of polypnea and rhonchi in the two groups showed similar decreases, an improvement mainly due to the antibiotic. No adverse events occurred and no adverse changes in laboratory parameters were observed. It is concluded that the combination of erdosteine and amoxicillin is a safe medication which is clinically superior to that of the antibiotic combined with placebo, especially in regard to the effects on cough

    Efficacy and safety of inhaled budesonide delivered once or twice daily via HFA-134a in mild to moderate persistent asthma in adult patients. Comparison with budesonide CFC

    Get PDF
    AbstractThis study was undertaken to investigate whether budesonide 400μg twice daily (Chiesi Farmaceutici S.p.A.) given with the HFA-134a propellant is equivalent in efficacy and safety to the same dose regimen delivered with the marketed CFC product in adult asthmatics with mild to moderate persistent asthma; the effects of budesonide HFA 800μg once daily were also studied. After a 2-week run-in, a total number of 98, 103 and 97 patients were assigned to the 12-week treatment with budesonide given with HFA or CFC twice daily (morning and evening), or HFA once daily (morning), respectively. The main outcome variable morning PEFR, as well as evening PEFR and clinical symptoms (day-time and night-time asthma attacks, number of asthma-induced night-time awakenings and overall symptoms’ scores) were measured daily by patients. Other standard pulmonary function testing were measured at clinic visits. A blood sample for morning serum dosing (8.00–10.00 AM) was taken at baseline and at endpoint. Adverse events and vital signs were also recorded.Significant improvements at endpoint in morning and evening PEFR, as well as in clinic PEFR and MEF50, were observed in both the twice daily groups only. An exact proof of equivalence between HFA and CFC given twice daily was demonstrated for the primary parameters, morning PEFR (equivalence pre-defined limits were ±40.27l/min, difference between means=4.0l/min and 95% CI −6.9–14.9) and secondary parameters as evening PEFR: (limits ±40.19l/min, difference between means=2.1l/min and 95% Confidence interval (CI) −9.4–13.5) and FEV1 (limits ±0.27l, difference between means=0.0l and 95% CI −0.11–0.10). Less evident (but within limits) proofs of equivalence were shown in the comparisons with the once daily group. No substantial differences between the three groups were observed for the other efficacy variables, including symptoms and use of rescue salbutamol, which significantly improved over the run-in values in all groups.Minimal and non-significant decreases over pre-treatment values were observed in the three groups for morning serum cortisol levels: the analysis of individual data has shown a better outcome in the HFA twice daily regimen, compared with the other two groups. Again, a similar amount of patients in both the twice daily groups reported drug-related adverse events, which were more frequent in the once daily HFA group.Therefore, the results of this study have shown that inhaled budesonide given with new HFA-134a propellant can replace microgram-equivalent doses of the corresponding marketed CFC product when given twice daily. An overall maintainment and an unchanged risk-benefit ratio has emerged for budesonide HFA given once daily, which was however slightly inferior compared with the standard twice daily regimens
    corecore