LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease.

    Saraf, Santosh L / Hagar, Robert Ward / Idowu, Modupe / Osunkwo, Ifeyinwa / Cruz, Kimberly / Kuypers, Frans A / Brown, R Clark / Geib, James / Ribadeneira, Maria D / Schroeder, Patricia / Wu, Eric / Forsyth, Sanjeev / Kelly, Patrick F / Kalfa, Theodosia A / Telen, Marilyn J

    Blood advances

    2024  

    Abstract: Etavopivat is an investigational, once-daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study (https://clinicaltrials.gov/study/NCT03815695) was conducted to ... ...

    Abstract Etavopivat is an investigational, once-daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study (https://clinicaltrials.gov/study/NCT03815695) was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: one single-dose; two multiple ascending doses; one open-label [OL]. In the OL cohort, 15 patients (median age 33.0 [range, 17‒55] years received 400-mg etavopivat once daily for 12 weeks; 14 completed treatment. Consistent with the mechanism of PKR activation, increases in ATP and decreases in 2,3 diphosphoglycerate were observed and sustained over 12 weeks' treatment. This translated clinically to an increase in hemoglobin (mean maximal increase 1.6 [range, 0.8‒2.8] g/dL), with >1 g/dL increase in 11 (73%) patients during treatment. Additionally, oxygen tension at which hemoglobin is 50% saturated was reduced (P=.0007) with concomitant shift in point-of-sickling (P=.0034) to lower oxygen tension in oxygen-gradient ektacytometry. Hemolysis markers (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase) decreased from baseline, along with matrix metalloproteinase-9 and erythropoietin. In the OL cohort, adverse events (AEs) were mostly grade 1/2, consistent with underlying SCD; 5 patients had serious AEs. Vaso-occlusive pain episode was the most common treatment-emergent AE (n=7) in the OL cohort. In this first study of etavopivat in SCD, 400 mg once daily for 12 weeks was well-tolerated, resulting in rapid and sustained increases in hemoglobin, improved RBC physiology, and decreased hemolysis.
    Language English
    Publishing date 2024-04-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023012467
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 7153: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial.

    Forsyth, Sanjeev / Schroeder, Patricia / Geib, James / Vrishabhendra, Leela / Konstantinidis, Diamantis G / LaSalvia, Kari / Ribadeneira, Maria D / Wu, Eric / Kelly, Patrick / Kalfa, Theodosia A

    Clinical pharmacology in drug development

    2022  Volume 11, Issue 5, Page(s) 654–665

    Abstract: Etavopivat (FT-4202) is an orally administered, small-molecule allosteric activator of erythrocyte pyruvate kinase-R (PKR) in clinical development for the treatment of sickle cell disease and other hemoglobin disorders. This randomized, placebo- ... ...

    Abstract Etavopivat (FT-4202) is an orally administered, small-molecule allosteric activator of erythrocyte pyruvate kinase-R (PKR) in clinical development for the treatment of sickle cell disease and other hemoglobin disorders. This randomized, placebo-controlled, double-blind, first-in-human combination single-ascending dose and multiple-ascending dose phase 1 trial (NCT03815695) evaluated the safety and pharmacokinetics/pharmacodynamics of etavopivat in 90 healthy adult subjects. In 4 single-ascending dose cohorts, 8 participants were randomized 3:1 to a single oral dose of either etavopivat (n = 6) or placebo (n = 2). In four 14-day multiple-ascending dose cohorts, 12 participants were randomized 3:1 to 14 days of etavopivat (n = 9) or placebo (n = 3). In these studies, most treatment-emergent adverse events were of mild severity (grade 1) and none led to study discontinuation. Etavopivat exhibited a linear and time-independent pharmacokinetic profile (at doses ≤400 mg) and elicited the expected pharmacodynamic effects of PKR activation (decreased 2,3-diphosphoglycerate and increased adenosine triphosphate) and evidence of improved hemoglobin-oxygen affinity. In addition, pharmacodynamic responses were durable with effects continuing for 48 to 72 hours after the last dose, thereby supporting once-daily dosing. Food appeared to have no clinically meaningful effects on etavopivat exposure, thus facilitating administration with or without food. In conclusion, the evaluation of etavopivat in healthy subjects demonstrated proof of mechanism (PKR activation) without significant adverse events. This study also allowed for the selection of dose levels, projected to have an acceptable safety profile and provide therapeutic benefit, for evaluation in future trials in patients with sickle cell disease.
    MeSH term(s) Adult ; Anemia, Sickle Cell ; Dose-Response Relationship, Drug ; Double-Blind Method ; Hemoglobins ; Humans ; Pyruvate Kinase
    Chemical Substances Hemoglobins ; Pyruvate Kinase (EC 2.7.1.40)
    Language English
    Publishing date 2022-01-12
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649010-9
    ISSN 2160-7648 ; 2160-763X
    ISSN (online) 2160-7648
    ISSN 2160-763X
    DOI 10.1002/cpdd.1058
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.

    Afdhal, Nezam H / Dusheiko, Geoffrey M / Giannini, Edoardo G / Chen, Pei-Jer / Han, Kwang-Hyub / Mohsin, Aftab / Rodriguez-Torres, Maribel / Rugina, Sorin / Bakulin, Igor / Lawitz, Eric / Shiffman, Mitchell L / Tayyab, Ghias-Un-Nabi / Poordad, Fred / Kamel, Yasser Mostafa / Brainsky, Andres / Geib, James / Vasey, Sandra Y / Patwardhan, Rita / Campbell, Fiona M /
    Theodore, Dickens

    Gastroenterology

    2014  Volume 146, Issue 2, Page(s) 442–52.e1

    Abstract: Background & aims: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, ... ...

    Abstract Background & aims: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.
    Methods: Patients with HCV infection and thrombocytopenia (platelet count <75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy.
    Results: More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/μL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2.
    Conclusions: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/therapeutic use ; Benzoates/therapeutic use ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Hematologic Agents/therapeutic use ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Humans ; Hydrazines/therapeutic use ; Induction Chemotherapy ; Intention to Treat Analysis ; Interferon-alpha/therapeutic use ; Liver Cirrhosis/blood ; Liver Cirrhosis/complications ; Liver Cirrhosis/virology ; Maintenance Chemotherapy ; Male ; Middle Aged ; Platelet Count ; Polyethylene Glycols/therapeutic use ; Pyrazoles/therapeutic use ; Recombinant Proteins/therapeutic use ; Ribavirin/therapeutic use ; Thrombocytopenia/blood ; Thrombocytopenia/drug therapy ; Thrombocytopenia/virology ; Treatment Outcome ; Young Adult
    Chemical Substances Antiviral Agents ; Benzoates ; Hematologic Agents ; Hydrazines ; Interferon-alpha ; Pyrazoles ; Recombinant Proteins ; Polyethylene Glycols (30IQX730WE) ; Ribavirin (49717AWG6K) ; peginterferon alfa-2b (G8RGG88B68) ; peginterferon alfa-2a (Q46947FE7K) ; eltrombopag (S56D65XJ9G)
    Language English
    Publishing date 2014-02
    Publishing country United States
    Document type Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2013.10.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ui V Zs.44: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 572: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article: Ertapenem monotherapy versus combination therapy with ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections in adults.

    Yellin, Albert E / Hassett, James M / Fernandez, Alvaro / Geib, James / Adeyi, Ben / Woods, Gail L / Teppler, Hedy

    International journal of antimicrobial agents

    2002  Volume 20, Issue 3, Page(s) 165–173

    Abstract: The efficacy and safety of intravenous (IV) ertapenem, 1 and 1.5 g once a day, for treatment of adults with complicated intra-abdominal infection were compared with those of IV ceftriaxone 2 g once a day plus IV metronidazole 500 mg every 8 h. After at ... ...

    Abstract The efficacy and safety of intravenous (IV) ertapenem, 1 and 1.5 g once a day, for treatment of adults with complicated intra-abdominal infection were compared with those of IV ceftriaxone 2 g once a day plus IV metronidazole 500 mg every 8 h. After at least 3 days of IV therapy and satisfactory clinical response, patients could be switched to oral ciprofloxacin plus metronidazole. Fifty-nine patients were randomized to receive ertapenem 1 g and 51 to receive ertapenem 1.5 g; 55 patients were randomized to each comparator group. At the test of cure, 4-6 weeks post therapy, in the 1 g cohort, 84% (26/31) of patients treated with ertapenem and 85% (35/41) with comparator therapy had a favourable clinical and microbiological assessment. Success rates in the 1.5 g cohort were 83% (22/29) and 77% (24/31) in the ertapenem and comparator groups, respectively. Drug-related adverse events were generally similar in both treatment groups. Ertapenem 1 or 1.5 g once a day followed by optional oral therapy appeared similar to combined therapy with ceftriaxone plus metronidazole with the same optional oral switch for treatment of complicated intra-abdominal infections in adults. Although not compared directly in a randomized fashion, the efficacy and safety profiles of ertapenem 1 and 1.5 g appeared comparable. Ertapenem was generally well tolerated and had an overall safety profile similar to ceftriaxone plus metronidazole.
    MeSH term(s) Abdomen/microbiology ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents/administration & dosage ; Anti-Infective Agents/adverse effects ; Anti-Infective Agents/therapeutic use ; Bacterial Infections/drug therapy ; Ceftriaxone/administration & dosage ; Ceftriaxone/adverse effects ; Ceftriaxone/therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Ertapenem ; Female ; Humans ; Injections, Intravenous ; Lactams ; Male ; Metronidazole/administration & dosage ; Metronidazole/adverse effects ; Metronidazole/therapeutic use ; Middle Aged ; beta-Lactams
    Chemical Substances Anti-Bacterial Agents ; Anti-Infective Agents ; Lactams ; beta-Lactams ; Metronidazole (140QMO216E) ; Ceftriaxone (75J73V1629) ; Ertapenem (G32F6EID2H)
    Language English
    Publishing date 2002-09
    Publishing country Netherlands
    Document type Clinical Trial ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/s0924-8579(02)00160-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3368: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 500: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top