A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia.

Aims: TAK-041 (NBI-1065846), an orally available, investigational, small molecule agonist of GPR139, an orphan G-protein-coupled receptor, has shown promise in preclinical studies for the treatment of symptoms associated with schizophrenia. Here, we report the results from a phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy adults and exploratory efficacy assessment of TAK-041 as adjunctive therapy to antipsychotics in adults with stable schizophrenia (ClinicalTrials.gov: NCT02748694).

Mucus plugging, air trapping, and bronchiectasis are important outcome measures in assessing progressive childhood cystic fibrosis lung disease.

Objective: To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements.

Methods: Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV ) 99 [12.

Pharmacokinetic Interaction Between Fingolimod and Carbamazepine in Healthy Subjects.

This open-label, single-sequence study in healthy subjects investigated the effects of steady-state carbamazepine on the pharmacokinetic (PK) profile of a single 2-mg dose of fingolimod. In period 1, a single oral dose of fingolimod 2 mg (day 1) was followed by PK and safety assessments up to 36 days. In period 2, carbamazepine was administered in flexible, up-titrated doses (600 mg twice daily maximum) for 49 days.

Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial.

Introduction: AQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia.

Methods: This was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia.

Cardiac Effects of Siponimod (BAF312) Re-initiation After Variable Periods of Drug Discontinuation in Healthy Subjects.

Purpose: The goal of this study was to investigate the effect of siponimod treatment re-initiation on the initial negative chronotropic effects and cardiac rhythm after variable drug discontinuation periods.

Methods: This partially double-blind, randomized, placebo-controlled study was conducted in healthy subjects. Siponimod doses (0.