A Phase 1 Study in Healthy Subjects to Evaluate the Safety and Pharmacokinetics of a Human Monoclonal Antibody (S315) Against Diphtheria Toxin.

Background: Diphtheria is a recurrent threat with endemic still occurs in many parts of the world. The standard of care is horse serum-derived diphtheria antitoxin (eDAT), which is in critical short supply globally. S315 is a fully human, monoclonal immunoglobulin G1 neutralizing antibody, specific to the receptor-binding domain of diphtheria toxin.

Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity.

Objective: Glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonists may provide greater weight loss than agonists targeting the GLP-1 receptor alone. We report results from three phase 1 trials investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of the glucagon/GLP-1 receptor co-agonist NNC9204-1177 (NN1177) for once-weekly subcutaneous use in adults with overweight or obesity.

Methods: Our focus was a 12-week, multiple ascending dose (MAD), placebo-controlled, double-blind trial in which adults (N = 99) received NN1177 (on an escalating dose regimen of 200, 600, 1300, 1900, 2800, 4200 and 6000 μg) or placebo.

A Phase I, Open-label, Randomized, Crossover Study of the Relative Bioavailability of Capsule and Granule Formulations of Selumetinib.

Purpose: Selumetinib (ARRY-142886) is an oral, potent, and highly selective allosteric mitogen-activated protein kinase kinase 1/2 inhibitor approved for the treatment of pediatric patients (≥2 years of age) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. This Phase I crossover study (NCT03649165) evaluated the pharmacokinetic properties and palatability of a new granule formulation of selumetinib.

Methods: Healthy volunteers were randomized to 1 of 2 sequences; selumetinib granule (25 mg) followed by selumetinib capsules (50 mg [2 × 25 mg]) and vice versa.

AZD5634, an inhaled ENaC inhibitor, in healthy subjects and patients with cystic fibrosis.

Background: Epithelial sodium channel (ENaC) inhibitors may offer clinical benefit in cystic fibrosis (CF); however, data are limited. We report the outcomes of a Phase I (NCT02679729) and a Phase Ib (NCT02950805) study of AZD5634, a novel inhaled ENaC inhibitor.

Methods: A Phase I, first-in-human, single-blind, placebo-controlled, single ascending dose, sequential dose group study assessed the safety, tolerability, and pharmacokinetics of AZD5634 in healthy subjects (n=53) in part A following inhaled doses up to 1700 µg, and, in part B, following administration of single inhaled (1700 µg) and intravenous (65 µg) doses.