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Bengt I Eriksson - One of the best experts on this subject based on the ideXlab platform.

  • an open label study of the pharmacokinetics and pharmacodynamics of dabigatran etexilate 150 mg once daily in caucasian patients with Moderate Renal Impairment undergoing primary unilateral elective total knee or hip replacement surgery
    Thrombosis Research, 2016
    Co-Authors: Bengt I Eriksson, Joachim Stangier, Martin Feuring, Zsolt Mikuska, Jean Amiral, Sebastian Haertter, Gerhard Nehmiz, Jeffrey I Weitz
    Abstract:

    Abstract Background In adults with Moderate Renal Impairment (creatinine clearance [CrCl] 30–50 mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150 mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. Methods Single-arm, open-label phase 4 study ( NCT01184989 ) in Caucasian patients receiving dabigatran etexilate 75 mg 1–4 h after surgery and 150 mg qd on days 2–10 (TKR) or days 2–35 (THR). Plasma total dabigatran concentrations (day 6 ± 1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot® Thrombin Inhibitors). Results Of 112 patients (mean CrCl 42.5 mL/min, age 79.1 years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5 ng/mL (10th–90th percentile 19.7–120) and 166 ng/mL (49.1–364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50–500 ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of ± 15%. Conclusions These findings in Caucasians with Moderate Renal Impairment undergoing THR or TKR support the use of the 150 mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful.

  • thromboprophylaxis with dabigatran etexilate in patients over seventy five years of age with Moderate Renal Impairment undergoing or knee replacement
    International Orthopaedics, 2012
    Co-Authors: Ola E Dahl, Andreas A Kurth, Nadia Rosencher, Herbert Noack, Andreas Clemens, Bengt I Eriksson
    Abstract:

    Purpose Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced Renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation.

  • erratum to thromboprophylaxis in patients older than 75 years or with Moderate Renal Impairment undergoing knee or hip replacement surgery
    International Orthopaedics, 2012
    Co-Authors: Ola E Dahl, Andreas A Kurth, Nadia Rosencher, Herbert Noack, Andreas Clemens, Bengt I Eriksson
    Abstract:

    Erratum to: International Orthopaedics (SICOT) DOI 10.1007/s00264-011-1393-5 The Article Title of the original publication of this paper contained an error. The correct Article Title should have been “Thromboprophylaxis in patients older than 75 years or with Moderate Renal Impairment undergoing knee or hip replacement surgery”.

Socrates E Papapoulos - One of the best experts on this subject based on the ideXlab platform.

Kenneth G Saag - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of febuxostat extended release and immediate release in patients with gout and Moderate Renal Impairment phase ii placebo controlled study
    Arthritis Research & Therapy, 2018
    Co-Authors: Lhanoo Gunawardhana, Andrew Whelton, Barbara Hunt, Majin Castillo, Michael Becker, Kenneth G Saag
    Abstract:

    Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and Moderate Renal Impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min). This was an exploratory, 3-month, phase II, multicenter, placebo-controlled, double-blind proof-of-concept study. Patients (n = 189) were randomized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg, XR 40 mg, IR 80 mg, or XR 80 mg once daily. Endpoints included: proportion of patients with serum uric acid (sUA) < 5.0 mg/dl at month 3 (primary endpoint), proportion of patients with sUA < 6.0 mg/dl at month 3, and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months. At month 3, all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl (p < 0.05 vs placebo). A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg (p = 0.034); proportions were similar in the IR 80 mg and XR 80 mg groups. Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 (p < 0.05 vs placebo) and experienced ≥ 1 gout flare (significant for all comparisons, except XR 40 mg). Incidences of treatment-related adverse events were low across all treatment groups; the majority were mild or Moderate with no apparent trends correlating with IR or XR doses. The most common treatment-emergent adverse event was hypertension. One death (unrelated to the study drug) was reported. These exploratory data demonstrate that febuxostat (XR and IR) formulations were effective and well tolerated in patients with gout and Moderate Renal Impairment. ClinicalTrials.gov, NCT02128490 Registered on 29 April 2014.

Andreas Clemens - One of the best experts on this subject based on the ideXlab platform.

  • observational study of dabigatran etexilate 150 mg in patients with Moderate Renal Impairment undergoing elective total hip or knee replacement
    Thrombosis Research, 2016
    Co-Authors: Charlesmarc Samama, Nadia Rosencher, Andreas Clemens, Eva Kleine, Martin Feuring, Martina Brueckmann, Jenny Gullberg, Simon P Frostick
    Abstract:

    Abstract Introduction The standard dabigatran etexilate dosage for prevention of venous thromboembolism (VTE) after elective total hip or knee replacement (THR/TKR) is 220mg once daily (qd), with 150mg qd for patients with Moderate Renal Impairment. As clinical trial experience in patients with Moderate Renal Impairment was limited at the time of approval, we conducted an observational study to evaluate the 150mg qd dose. Materials and methods This open-label, prospective, uncontrolled, observational study in patients with creatinine clearance (CrCl) 30–50mL/min was conducted in seven European countries. Patients received 75mg dabigatran etexilate 1–4h after surgery and 150mg qd on days 2–10 (TKR) or 2–35 (THR), per the European Summary of Product Characteristics. Coprimary outcomes were major bleeding events (MBEs) and a composite of symptomatic VTE and all-cause mortality. Results 428 Renally impaired patients with median CrCl 43.4mL/min (range 30.0–49.9), and median age 80years (range 32–96) received dabigatran etexilate: median treatment duration THR 31days, TKR 28days. Ten MBEs occurred in nine patients (2.1%; 95% confidence interval [CI]: 1.0–4.0; THR 1.8%; TKR 2.4%); none were fatal or involved a critical organ. Symptomatic VTE and all-cause mortality occurred in three patients (0.7%; 95% CI: 0.1–2.0; THR 0.9%; TKR 0.5%). Overall, 54 patients discontinued treatment prematurely, including 35 due to an adverse event (nine bleeding-related) and 16 switching to another anticoagulant. Conclusions Dabigatran etexilate 150mg qd had a good safety profile and was efficacious in fragile, elderly, Renally impaired patients undergoing THR or TKR. These findings from the clinical practice setting add to the existing clinical trial data.

  • thromboprophylaxis with dabigatran etexilate in patients over seventy five years of age with Moderate Renal Impairment undergoing or knee replacement
    International Orthopaedics, 2012
    Co-Authors: Ola E Dahl, Andreas A Kurth, Nadia Rosencher, Herbert Noack, Andreas Clemens, Bengt I Eriksson
    Abstract:

    Purpose Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced Renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation.

  • erratum to thromboprophylaxis in patients older than 75 years or with Moderate Renal Impairment undergoing knee or hip replacement surgery
    International Orthopaedics, 2012
    Co-Authors: Ola E Dahl, Andreas A Kurth, Nadia Rosencher, Herbert Noack, Andreas Clemens, Bengt I Eriksson
    Abstract:

    Erratum to: International Orthopaedics (SICOT) DOI 10.1007/s00264-011-1393-5 The Article Title of the original publication of this paper contained an error. The correct Article Title should have been “Thromboprophylaxis in patients older than 75 years or with Moderate Renal Impairment undergoing knee or hip replacement surgery”.

  • economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with Moderate Renal Impairment undergoing total knee or hip replacement
    Thrombosis and Haemostasis, 2009
    Co-Authors: Sorrel Wolowacz, Herbert Noack, Andreas Clemens, Neil Roskell, Jonathan M Plumb, Paul A Robinson, G Dolan, I J Brenkel
    Abstract:

    Oral dabigatran etexilate is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement or total hip replacement. We investigated the cost-effectiveness of the 150 mg once daily (od) dose recommended for patients aged over 75 or with Moderate Renal Impairment, from a United Kingdom National Health Service perspective. Dabigatran etexilate was compared with subcutaneous enoxaparin 40 mg od, using a decision model. Risks for VTE and bleeding were derived from subgroup analyses of the phase III trials. Dabigatran etexilate was less costly than enoxaparin; cost savings varied from £62 to £274 (base-case analyses) and were primarily due to differences in administration costs. Results were robust across a range of sensitivity analyses. Dabigatran etexilate 150 mg od is cost saving compared with enoxaparin 40 mg od in patients aged over 75years and in patients with Moderate Renal Impairment, with comparable efficacy and safety.

Ofri Mosenzon - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of oral semaglutide in patients with type 2 diabetes and Moderate Renal Impairment pioneer 5 a placebo controlled randomised phase 3a trial
    The Lancet Diabetes & Endocrinology, 2019
    Co-Authors: Ofri Mosenzon, Simon Heller, Richard E. Pratley, Signe Rosenlund, Jan W. Eriksson, Thozhukat Sathyapalan, Thalia Marie Blicher, Ole H. Hels, Cyrus Desouza, R Abramof
    Abstract:

    Summary Background Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with Renal Impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and Moderate Renal Impairment. Methods This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and Renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6; p Interpretation Oral semaglutide was effective in patients with type 2 diabetes and Moderate Renal Impairment, potentially providing a new treatment option for this population. Safety, including Renal safety, was consistent with the GLP-1 receptor agonist class. Funding Novo Nordisk A/S.

  • 1004-P: Oral Semaglutide vs. Placebo in Patients with Type 2 Diabetes and Moderate Renal Impairment: PIONEER 5
    Diabetes, 2019
    Co-Authors: Ofri Mosenzon, Simon Heller, Richard E. Pratley, Signe Rosenlund, Jan W. Eriksson, Thozhukat Sathyapalan, Thalia Marie Blicher, Ole H. Hels, Cyrus Desouza
    Abstract:

    Patients (pts) with T2D and Renal Impairment have limited glucose-lowering treatment options. Oral semaglutide (sema) 14 mg once daily (N=163) was compared with placebo (pbo, N=161) in a 26-week, randomized, phase 3a trial (NCT02827708) in pts with T2D and Moderate Renal Impairment (eGFR 30-59 mL/min/1.73 m2), receiving 1-2 glucose-lowering agents (could include basal insulin). Endpoints: change in HbA1c (primary) and body weight (BW, secondary) to week 26. Two estimands were defined: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized pts. Oral sema was superior to (treatment policy) and significantly better than (trial product) pbo in reducing HbA1c and BW (Table). More pts reached HbA1c, BW loss, and composite targets with oral sema. At follow-up, eGFR was unchanged. Fewer pts on oral sema required rescue medication (4 vs. 10%). Adverse events were more frequent with oral sema (74 vs. 65%), most often mild/Moderate nausea (19 vs. 7%). More patients on oral sema prematurely discontinued trial product (15 vs. 5%), mainly due to nausea and vomiting. In conclusion, in pts with T2D and Moderate Renal Impairment, oral sema provided superior glycemic control and BW loss compared to pbo at 26 weeks, did not appear to affect Renal function, and was well tolerated in line with the population and GLP-1RA class. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker9s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S. Rosenlund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.W. Eriksson: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Zealand Pharma A/S. Consultant; Self; Novo Nordisk A/S. Speaker9s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. T. Sathyapalan: Speaker9s Bureau; Self; Novo Nordisk Foundation. Other Relationship; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Sanofi-Aventis. T.M. Blicher: Employee; Self; Novo Nordisk A/S. O.H. Hels: Employee; Self; Novo Nordisk A/S. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi US. Funding Novo Nordisk A/S