Developing Topics.

Background: ALZ-101 is a vaccine comprised of stabilised oligomeric Aβ42 that stimulates a humoral immune response primarily targeting a toxic, low-abundant oligomeric form of Aβ. Part A of a clinical Phase 1b trial (ALZ-C-001; NCT05328115) was recently concluded with the objectives to assess the safety, tolerability and immunogenicity of ALZ-101 in subjects with mild AD or MCI due to AD.

Methods: Participants were randomised to receive placebo (n = 6), 125 µg (n = 10) or 250 µg (n = 10) doses of ALZ-101 at weeks 0, 4, 8, and 16.

A randomized pharmacokinetic-pharmacodynamic evaluation of the potential biosimilar interferon beta-1a product, CinnoVex®.

Background: The objective of the trial was to evaluate the bioequivalence of the interferon beta-1a (IFN beta-1a) biosimilar product candidate CinnoVex® with the reference product Avonex® by comparing the pharmacokinetics/pharmacodynamics (PK/PD), safety and immunogenicity of the two products in healthy subjects.

Methods: A total of 41 healthy subjects were randomized in a two-stage design to receive single doses of CinnoVex® and Avonex®. The primary PK endpoint was the area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC).

Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers.

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic Technology (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729).

Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time.

Objective: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated.

Safety and efficacy of AMG 714 in adults with coeliac disease exposed to gluten challenge: a phase 2a, randomised, double-blind, placebo-controlled study.

Background: Interleukin 15 (IL-15) is implicated in the pathophysiology of coeliac disease. AMG 714 is the first anti-IL-15 monoclonal antibody to be investigated for the treatment of coeliac disease. We aimed to investigate the effects of AMG 714 in patients with coeliac disease who underwent gluten challenge.

Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects.

Nasal spray formulations of naloxone, a mu-opioid receptor (MOR) antagonist, are currently used for the treatment of opioid overdose. They may have additional therapeutic utility also in the absence of opioid agonist drugs, but the onset and duration of action at brain MORs have been inadequately characterized to allow such projections. This study provides initial characterization of brain MOR availability at high temporal resolution following intranasal (IN) naloxone administration to healthy volunteers in the absence of a competing opioid agonist.

The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure.

Background: The primary aim of this study was to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves endothelium-dependent brachial artery flow-mediated vasodilatation (FMD) in volunteers with borderline hypertension. The secondary aim of the study was to test whether the investigational product would improve endothelium-independent nitrate-mediated vasodilatation (NMD).

Methods: This was a single centre, repeated-dose, double-blind, placebo-controlled, crossover study in 60 otherwise healthy subjects (26 men, 34 women; aged 40-65 years) with borderline hypertension (blood pressure 130-139/85-89 mmHg) or unmedicated mild hypertension (blood pressure 140-165/90-95 mmHg).