Joel M. Neutel

Effects of renal impairment on the pharmacokinetics, safety, and tolerability of pudexacianinium (ASP5354) after IV administration: a mechanistic exploration

Tomoki Kojima, Masako Saitō, Toshihiro Matsuda, Neal Simmons et autres

PURPOSE: To elucidate mechanisms of renal excretion of pudexacianinium (ASP5354) and evaluate renal impairment effects on pharmacokinetics, safety, and tolerability of pudexacianinium. METHODS: Transcellular transport and transporter-mediated uptake of pudexacianinium were investigated in cells expressing human renal drug transporters P-gp, BCRP, OAT1, …

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Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension

Akshay S. Desai, Adam Karns, Jolita Badarienė, Ahmad Aswad et autres

Importance: In prior monotherapy studies of patients with hypertension, single subcutaneous doses of zilebesiran, an investigational RNA interference therapeutic, reduced serum angiotensinogen levels and systolic blood pressure (SBP) at 3 and 6 months. Objective: To evaluate the efficacy and safety of zilebesiran …

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Safety and Immunogenicity of Concomitant Administration and Combined Administration of Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine with or Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age

Joel M. Neutel, Rahsan Erdem, Qin Jiang, Kevin Cannon et autres

Concomitant administration may improve vaccination rates. This analysis of a phase 1/2 randomized study included 1073 healthy ≥65-year-olds who previously received ≥3 mRNA COVID-19 vaccine doses. Participants received concomitantly administered RSVpreF and bivalent BA.4/BA.5-adapted BNT162b2 vaccine (concomitant administration) with or without quadrivalent …

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First‐in‐Human Evaluation of Safety, Pharmacokinetics and Muscle Glycogen Lowering of a Novel Glycogen Synthase 1 Inhibitor for the Treatment of Pompe Disease

Julie C. Ullman, Ryan A. Dick, Daniela Linzner, Todd Minga et autres

Pompe disease is a rare glycogen storage disease caused by mutations in the enzyme acid α‐glucosidase (GAA) resulting in pathological accumulation of glycogen in muscle tissues leading to progressive weakness and respiratory dysfunction. Enzyme replacement therapy (ERT) with GAA is currently the …

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609-P: Effects of Oligomalt (OM), a New Slowly Digestible Carbohydrate (SDC), on Postprandial (PP) Glucose, Insulin, and GLP-1 Trajectories Compared with Maltodextrin (MD) in People with Obesity (PwO) or Type 2 Diabetes (T2D)—A Double-Blind RCT

Odd Erik Johansen, Joel M. Neutel, Sanjay Gupta, BARBARA MARIANI et autres

Introduction & Objective: to assess glucometabolic effects of OM, a novel fully digestible SDC. Methods: In a cross-over RCT, we tested 33g and 50g of OM/MD in PwO (n=26, mean age 44 yrs, BMI 29.9 kg/m2, HbA1c 5.3%), and 50g in people …

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22-PUB: Machine Learning–Based Optimization of Patient Eligibility for Oral Insulin Treatment—A Post Hoc Analysis of Phase III Trial Results

Miriam Kidron, Elad Berkman, Oshri Machluf, Raviv Pryluk et autres

Background & Objectives: The growing shift toward implementation of precision medicine to improve the prospects of achieving treatment targets requires comprehensive profiling of an array of patient-specific data. Research efforts in this arena include review of anthropometric, epidemiological and clinical features to …

ZILEBESIRAN AS ADD-ON THERAPY IN PATIENTS WITH HYPERTENSION INADEQUATELY CONTROLLED WITH A STANDARD ANTIHYPERTENSIVE MEDICATION: EFFICACY AND SAFETY RESULTS FROM THE KARDIA-2 STUDY

Manish Saxena, Ahmad Aswad, Jolita Badarienė, Farhana Kazi et autres

Objective: Zilebesiran is an investigational RNA interference therapeutic that targets hepatic angiotensinogen, the most upstream precursor of the renin-angiotensin system. In the Phase 2 KARDIA-1 study, single subcutaneous (SC) doses of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood …

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Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID‐19

Ravi Shankar Prasad Singh, Robert R. LaBadie, Sima S. Toussi, Haihong Shi et autres

Nirmatrelvir, a novel, potent, orally bioavailable severe acute respiratory syndrome coronavirus 2 main protease inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID-19 in individuals at increased risk of progression to severe disease. …

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98-OR: Oral Insulin Alleviates Liver Fibrosis and Reduces Fat in Patients with NASH and Type 2 Diabetes—Results of Phase II Clinical Trial

Yuval Ishay, Joel M. Neutel, Yotam Kolben, Ram Gelman et autres

NAFLD is the most common liver disorder in the USA. NASH is an advanced form of NAFLD and a leading cause of end-stage liver disease and indication for liver transplantation. Insulin resistance and inflammation underlie the pathogenesis of the disease. This double-blind, …

Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID ‐19, in Subjects With Renal Impairment

Sima S. Toussi, Joel M. Neutel, J. Navarro, Richard Alfred Preston et autres

Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID-19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when …

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41-LB: A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of a Natural Powder Blend (Mulberry Leaf Extract [MLE], Vitamin D, Chromium, and Fiber) on Postprandial (PP) Metabolic Response in Type 2 Diabetes (T2D)

Mafauzy Mohamed, ROBERTO ZAGURY, KALPANA BHASKARAN, Joel M. Neutel et autres

MLE contains iminosugar alkaloids (of which 1-deoxynojirimycin [DNJ] is most abundant) , and phenolic and flavonoid functional ingredients, which can modulate PP metabolism. We tested a 2 g powder blend of 250 mg MLE (containing 12.5 mg DNJ) combined with fibre (1.75 …

37-LB: Very-Low-Dose Premeal Whey Protein Microgels Reduce Postprandial (PP) Glucose in Type 2 Diabetes: A Randomized, Placebo-Controlled Crossover Study

Luiz Henrique de Gregório, Ian J. Neeland, Roberto Zagury, Bo Åhrén et autres

Whey protein (WP), found in dairy products, is rich in branched chain amino acids and bioactive peptides that stimulate the secretion of incretin hormones and insulin, but has typically required relatively high caloric doses. Technologies enhancing absorption could enable use of a …